About all

Ejaculatory muscles: ejaculation | Definition & Process

Содержание

ejaculation | Definition & Process

ejaculation, the release of sperm cells and seminal plasma from the male reproductive system. Ejaculation takes place in two phases: in the first, or emission, stage, sperm are moved from the testes and the epididymis (where the sperm are stored) to the beginning of the urethra, a hollow tube running through the penis that transports either sperm or urine; in the second stage, ejaculation proper, the semen is moved through the urethra and expelled from the body.

Sperm cells that are stored in the male body are not capable of self-movement because of the acidity of the accompanying fluids. When the sperm receive fluids, called seminal plasma, from the various internal accessory organs (prostate gland, ejaculatory ducts, seminal vesicles, and bulbourethral glands), the acidity decreases. As they leave the body, the sperm receive oxygen, which is vital to motility. Unable to leave the male body by their own motivation, the sperm cells are transported by muscular contractions. During the emission phase, the muscles around the epididymis and ductus deferens (the tube extending from the epididymis) contract to push the sperm into the prostate and urethra. During ejaculation, the semen is expelled by strong spasmodic contractions of the bulbocavernosus muscle, which encircles the corpus spongiosum (the structure in the penis that encloses the urethra). The whole process of ejaculation is accomplished by nerve impulses received from the penis; once ejaculation is started it becomes a reflex reaction that cannot be voluntarily interrupted.

spermatogenesis

Spermatogenesis is the origin and development of the sperm cells within the male reproductive organs, the testes. Sperm cells are produced within the testes in structures called seminiferous tubules. Once the sperm has matured, it is transported through the long seminiferous tubules and stored in the epididymis of the testes until it is ready to leave the male body.

Encyclopædia Britannica, Inc.

The seminal fluid is not passed from the various accessory glands simultaneously. A small amount of mucuslike secretion is first passed from the bulbourethral and urethral glands to flush out the urethra and prepare it for the sperm. Next follows the fluid from the prostate gland, and then that from the seminal vesicles. Finally, the fluid actually containing the sperm is ejaculated. After the bulk of the sperm cells have passed, more fluids follow and again flush out the urethra. The total volume of the ejaculate averages between 2 and 5 millilitres (0.12 to 0.31 cubic inch) in the human; of this, only about 1 to 5 percent are actually sperm cells. The other constituents of semen include nutrients, water, salts, waste products of metabolism, and cellular debris. The secretions of the testes and accessory glands are produced under the influence of the male hormone testosterone; without sufficient testosterone the glands degenerate and cannot secrete fluids. See also erection.

The Editors of Encyclopaedia BritannicaThis article was most recently revised and updated by John P. Rafferty.

emphasis on orgasm and ejaculation

Fertil Steril. Author manuscript; available in PMC 2016 Jun 7.

Published in final edited form as:

PMCID: PMC4896089

NIHMSID: NIHMS789951

, M.D., M.Sc.,a,b, M.D., M.A.S.,b and , M.D.b

Amjad Alwaal

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Benjamin N. Breyer

bDepartment of Urology, University of California, San Francisco, California

Tom F. Lue

bDepartment of Urology, University of California, San Francisco, California

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Reprint requests: Amjad Alwaal, M. D., M.Sc., King Abdulaziz University, Department of Urology, P. O. Box 80215, Jeddah, Saudi Arabia 21589 ([email protected]).The publisher’s final edited version of this article is available at Fertil SterilSee other articles in PMC that cite the published article.

Abstract

Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process.

Keywords: Erectile function, male sexual function, ejaculation, orgasm

Ejaculatory dysfunction is one of the most common male sexual dysfunctions that is often mis-diagnosed or disregarded. At present, there is no definitive cure for ejaculatory dysfunctions (1). New research on the physiology of ejaculation keeps emerging to identify targets of treatment. However, knowledge about this topic is still lacking. In the present article, we summarize the current literature on the physiology of ejaculation. We describe the anatomy of the organs involved and the erection physiology. We discuss the physiology of orgasm and ejaculation as two separate physiological processes. In addition, we describe the neurochemical and hormonal regulation of the ejaculation process.

FUNCTIONAL ANATOMY OF THE MALE GENITAL ORGANS

The male genital system consists of external and internal reproductive and sexual organs such as the penis, prostate, epididymis, and testes. shows the gross anatomy of the ejaculatory structures. provides a summary of the functional anatomy of these organs (2–5).

Gross anatomy of the ejaculation structures. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:15.)

TABLE 1

Summary of the functional anatomy of the male genital organs.

Organ Characteristics
Penis Composed of three chambers: paired corpora cavernosa (erectile bodies) and a midline ventral corpus spongiosum
 (contains urethra)
Main blood supply: internal pudendal artery
Somatic sensation: pudendal nerve (S2-S4)
Autonomic nerve fibers: cavernous nerves (pelvic plexus) contain both sympathetic (hypogastric plexus) and
 parasympathetic nerve fibers (S2-S4)
Urethra Four segments: prostatic urethra, membranous urethra (passes through the urogenital diaphragm), bulbar urethra,
 and penile urethra (ends with a small dilatation at the fossa navicularis near the meatus)
Cowper’s glands: located on both sides of the membranous urethra and open in the bulbar urethra
Veromontanum: small elevation of the posterior wall of the membranous urethra, related to ejaculatory ducts, prostatic
 utricle, and prostatic ducts
Testis It is divided by fibrous septa into many lobules containing seminiferous tubules
Leydig cells: main source of T production
Seminiferous tubules: contain germ cells and sertoli cells. Forms the rete testis inside the testis mediastinum
Rete testis: gives rise to 15–20 efferent ductules
Epididymis Posterior and superior to the testicle
Composed of head, body, and tail
Efferent ductules unite to form the convoluted duct of the epididymis
Becomes the vas deferens at the end of the tail
Vas deferens Muscular tube; typically 45 cm long and has a 2.5 mm diameter
It is a continuation of the epididymis
Joins the seminal vesicle duct to form the ejaculatory duct, which then drains into the veromontanum
Supplied by the vasal artery, a branch of the inferior vesical artery
Prostate Surrounds the prostatic urethra
Composed of 70% glandular component and 30% fibromuscular component
Arterial supply: inferior vesical and middle rectal arteries
Seminal
 vesicles
Paired structures; located lateral to the vas deferens
Typically 5 cm long and 1 cm wide
Joins the vas to form the ejaculatory duct
Arterial supply: inferior vesical and middle rectal arteries

PHYSIOLOGY OF ERECTION

The penile erection results from complex neurovascular mechanisms. Several central and peripheral neurological factors in addition to molecular, vascular, psychological and endocrino-logical factors are involved, and the balance between these factors is what eventually determines the functionality of the penis. In this section, we summarize some of those mechanisms.

Cerebral Control

Cerebrally controlled penile erections are induced through erotic visual stimuli or thoughts. The main cerebral structures involved in erection are contained within the medial preoptic area (MPOA) and paraventricular nucleus (PVN) in the hypothalamus (6). Dopamine is the most important brain neurotransmitter for erection, likely through its stimulation of oxytocin release (7). Another important neurotransmitter is norepinephrine, which is demonstrated through the erectogenic effect of the α-2 agonist (Yohimbine) (8). Several other brain neurotransmitters are involved in the erection process to varying degrees such as nitric oxide (NO), α-melanocyte stimulating hormone (α-MSH), and opioid peptides (9).

Autonomic Control

Parasympathetic stimulation is the main mediator for penile tumescence, although central suppression of the sympathetic nervous system also plays a role. Parasympathetic supply to the penis is derived from the sacral segments S2-S4 (10). However, patients with sacral spinal cord injury still maintain erections through psychogenic stimulation, although of less rigidity than normal. These psychogenic erections do not occur in patients with lesions above T9 (11), suggesting that the main mechanism for these erections is central suppression of sympathetic stimulation (12). Patients with lesions above T9 still may maintain reflexogenic erections. This implies that the main mechanism for reflexogenic tumescence is the preservation of the sacral reflex arc, which mediates erection through tactile penile stimulation (13, 14).

Molecular Mechanisms

The penis at baseline is in a flaccid state maintained by the contraction of corporal smooth muscles and constriction of cavernous and helicine arteries leading to moderate state of hypoxia with partial pressure of oxygen of 30–40 mm Hg (15). During sexual arousal, NO is released from cavernous nerve terminals through the action of neuronal NO synthase (16). The NO activates guanylate cyclase, which in turn converts guanosine triphosphate to cyclic guanosine monophosphate (15, 17), leading eventually to smooth muscle relaxation and vasodilation (18). Although the initiation of tumescence is through neuronal NO synthase, the maintenance of erection is through endothelial NO synthase (19). The eventual smooth muscle relaxation and vasodilation results in blood flowing into the paired corpora and filling of the sinusoids, with increased intracorporal pressure (to >100 mm Hg during full erection) and compression of the subtunical venules, markedly reducing the venous outflow (13).

PHYSIOLOGY OF ORGASM

There is no standard definition of orgasm. Each specialty such as endocrinology or psychology examines this activity from each one’s perspective, making it difficult to reach a consensus on the definition. Orgasm is generally associated with ejaculation, although the two processes are physiologically different (20). Certain physiological features are associated with orgasm, including hyperventilation up to 40 breaths/min, tachycardia, and high blood pressure (21). In fact, faster heart rate was found to be an indicator of “real” male orgasm during intravaginal intercourse, differentiating it from “fake” orgasm (22). Orgasm is also associated with powerful and highly pleasurable pelvic muscle contractions (especially ischiocavernosus and bulbocavernosus) (23), along with rectal sphincter contractions and facial grimacing (21). There is also an associated release and elevation in PRL and oxytocin levels after orgasm; however, the significance of this elevation is not entirely clear (24).

Studies using positron emission tomography, which measures changes in regional cerebral blood flow, have identified areas of activation in the brain during orgasm. Primary intense activation areas are noted to be in the mesodiencephalic transition zones, which includes the midline, the zona incerta, ventroposterior and intralaminar thalamic nuclei, the lateral segmental central field, the suprafascicular nucleus, and the ventral tegmental area. Strong increases were seen in the cerebellum. Decreases were noted at the entorhinal cortex and the amygdale (25).

Quality and intensity of orgasms are variable. For instance, short fast buildup of sexual stimulation toward orgasm is associated with less intense orgasms than slow buildup. Early orgasms are less satisfying than later orgasms in life as the person learns to accept the pleasure associated with orgasms. Lower levels of androgen are associated with weaker orgasms, such as in hypogonadism or in older age (20). It has been suggested that pelvic muscle exercises, particularly the bulbocavernosus and ischiocavernosus muscles, through contracting those muscles 60 times, 3 times daily for 6 weeks will enhance the pleasure associated with orgasm (20). However, the effort and time associated with such exercises prevent their utilization. The orgasm induced through deep prostatic massage is thought to be different from the orgasm associated direct penile stimulation. Although penile stimulation orgasms are associated with 4–8 pelvic muscle contractions, prostatic massage orgasms are associated with 12 contractions. Prostatic massage orgasms are thought to be more intense and diffuse than penile stimulation orgasms, but they require time and practice and are not liked by many men (20, 26, 27).

Following orgasm in men is a temporary period of inhibition of erection or ejaculation called the refractory period. This is a poorly understood phenomenon, with some investigators suggesting a central rather than spinal mechanism causing it (28). Elevated levels of PRL and serotonin after orgasm have been suggested as a potential cause; however, there is much debate about their exact role (29). More research is still needed in the area of male orgasm (20).

PHYSIOLOGY OF EJACULATION

Ejaculation is a physiological process heavily controlled by the autonomic nervous system. It consists of two main phases: emission and expulsion. The main organs involved in ejaculation are the distal epididymis, the vas deferens, the seminal vesicle, the prostate, the prostatic urethra, and the bladder neck (30).

Emission

The first step in the emission phase is the closure of bladder neck to prevent retrograde spillage of the seminal fluid into the bladder. This is followed by the ejection of prostatic secretions (10% of the final semen volume) containing acid phosphatase, citric acid, and zinc, mixed with spermatozoa from the vas deferens (10% of the volume) into the prostatic urethra. Subsequently, the fructose-containing seminal vesicle fluid alkalinizes the final ejaculatory fluid. The seminal vesicle fluid constitutes 75%–80% of the final seminal fluid. Cowper’s glands and periurethral glands produce a minority of the seminal fluid (1, 31). The organs involved in the ejaculation process receive dense autonomic nerve supply, both sympathetic and parasympathetic, from the pelvic plexus. The pelvic plexus is located retroperitoneally on either side of the rectum, lateral and posterior to the seminal vesicle (32). It receives neuronal input from the hypogastric and pelvic nerves in addition to the caudal paravertebral sympathetic chain (33). The sympathetic neurons play the predominant role in the ejaculation process. Their nerve terminals secrete primarily norepinephrine, although other neurotransmitters such as acetylcholine and nonadrenergic/noncholinergic also play important roles (34). The role of the hypogastric plexus in emission is best demonstrated clinically by the loss of emission after non-nerve sparing para-aortic lymph node dissection for testicular cancer (35), and induction of emission in paraplegic men through electrical stimulation of superior hypogastric plexus (35). Input from genital stimulation is integrated at the neural sacral spinal level to produce emission (36). The emission phase of ejaculation is also under a considerable cerebral control, and can be induced through physical or visual erotic stimulation (37).

Expulsion

Expulsion follows emission as the process of ejaculation climaxes, and refers to the ejection of semen through the urethral meatus. The semen is propelled through the rhythmic contractions of the pelvic striated muscles in addition to the bulbospongiosus and ischiocavernosus muscles (23). To achieve antegrade semen expulsion, the bladder neck remains closed, whereas the external urethral sphincter is open. The external sphincter and the pelvic musculature are under somatic control; however, there is no evidence that voluntary control plays a role in the expulsion process (30). The exact trigger for expulsion is unknown. It has been suggested that a spinal center is triggered during emission of seminal fluid into the prostatic urethra (38). However, there is mounting evidence through clinical and experimental studies to suggest that this is not the case. For instance, men can still have rhythmic contractions during orgasm despite “dry ejaculation,” for example, due to prostatectomy (23, 39, 40). This, in addition to the identification of spinal generator for ejaculation (SGE) in rats, led to the postulation that the process of expulsion is a continuum of the process initiated through emission, after reaching a certain spinal activation threshold (30, 41).

NEURONAL CONTROL OF EJACULATION

Ejaculation is heavily controlled by the nervous system. summarizes the reflex circuit necessary to elicit ejaculation.

Reflex circuit needed to establish ejaculation. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:18.)

Peripheral Nervous System

Afferents

The main sensory input from the penis comes from the dorsal nerve of the penis, which transmits sensation from the glans, prepuce, and penile shaft. It transmits signals to the upper and lower segments of the sacral spinal cord (42). The glans contains encapsulated nerve endings, termed Krause-Finger corpuscles, whereas the remaining penile shaft contains free nerve endings. Stimulation of these corpuscles potentiated by stimulation from other genital areas, such the perineum, testes, and penile shaft, play an important role in the ejaculation process (43). A secondary afferent route is through the hypogastric nerve, which runs through the paravertebral sympathetic chain to enter the spinal cord through the thoracolumbar dorsal roots (44). The sensory afferents terminate in the medial dorsal horn and the dorsal gray commissure of the spinal cord (45).

Efferents

The efferent peripheral nervous system constitutes of sympathetic, parasympathetic, and motor nervous components (46). The soma of the preganglionic sympathetic cell bodies involved in ejaculation are located in the intermedio-lateral cell column and in the central autonomic region of the thoracolumbar segments (T12-L1) (47). The preganglionic sympathetic fibers emerge from the ventral roots of the spinal cord and travel through the paravertebral sympathetic chain to relay either directly through the splanchnic nerve, or through relaying first in the celiac superior mesenteric ganglia and then through the intermesenteric nerve, to the inferior mesenteric ganglia (48). The hypogastric nerve then emanates from the inferior mesenteric ganglia to join the parasympathetic pelvic nerve to form the pelvic plexus, which then sends fibers to the ejaculation structures (49). The preganglionic parasympathetic cell bodies are located in the sacral parasympathetic nucleus. The sacral parasympathetic nucleus neurons travel then in the pelvic nerve to the post-ganglionic parasympathetic cells located in the pelvic plexus. The motor neurons involved in ejaculation are located in Onuf’s nucleus in the sacral spinal cord, which projects fibers through the motor component of the pudendal nerve to reach the pelvic musculature, including the bulbospongiosus, ischiocavernosus, and external urethral sphincter (50).

Central Nervous System

Spinal network

The thoracolumbar sympathetic, sacral parasympathetic (mainly sacral parasympathetic nucleus), and somatic sacral Onuf’s nucleus ejaculatory spinal nuclei play an important role in the integration of peripheral and cerebral input and coordinating output to the pelviperineal structures involved in ejaculation (46). An additional spinal center is the SGE located in laminae X and VII of L3-L4 spinal segments (51). The SGE contains spinal interneurons called lumbar spinothalamic cells, which project fibers to the parvocellular subparafascicular nucleus of the thalamus in addition to preganglionic sympathetic and parasympathetic neurons innervating the pelvis (41). The SGE stimulation elicits a complete ejaculatory response resulting in collection of motile spermatozoa in anesthetized rats (52). Further research on the SGE spinal center is still needed, and it is unclear whether it contains other cells than lumbar spinothalamic cells.

Brain network

Sensory and motor areas in the brain play an important role in the ejaculation, which requires a highly coordinated and integrated central process. The study by Holstege et al. (25) using positron emission tomography showed that certain areas in the brain are activated in the orgasm and ejaculation process. Furthermore, specific areas in the brain have been involved in the ejaculation process, as demonstrated in animal immunohistochemical studies examining Fos protein pattern of expression (53–56), and confirmed using a serotonin 1A subtype receptor agonist proejaculatory pharmacologic agent in rats (57). These are discrete areas within the posteromedial bed nucleus of stria terminalis, the parvicellular part of the subparafascicular thalamus, the posterodorsal preoptic nucleus, and the posterodorsal medial amygdaloid nucleus. There are reciprocal connections that link those areas to the MPOA of the hypothalamus, a brain area with a well-established role in controlling sexual behavior as demonstrated by anatomical and functional studies (54, 55, 58). Electrical or chemical stimulation of the MPOA elicited ejaculation (59–62), whereas an MPOA lesion was shown to abolish both phases of ejaculation (63). No direct connections of MPOA to the spinal centers for ejaculation were found on neuroanatomical studies; however, there are projections of MPOA to other regions in the brain involved in ejaculation, such as PVN, the periaqueductal gray, and the paragigantocellular nucleus (nPGi) (64–66).

The PVN projects to pudendal motor neurons located in the L5-L6 spinal segment in addition to autonomic preganglionic neurons in the lumbosacral spinal cord in rats (45, 67, 68). It also projects to nPGI in the brainstem (69). Bilateral lesions of the PVN with N-methyl-D-aspartate (NMDA) results in a one-third reduction of the seminal ejaculate material weight (70). The parvicellular part of the subparafascicular thalamus was found to send projections to bed nucleus of stria terminalis, medial amygdala (MeA), and MPOA (71, 72) and receives input from lumbar spinothalamic cells (51). The precise role of these regions is still unclear but they are likely involved in relaying genital signals to MPOA (53, 55). The brainstem regions (nPGI and periaqueductal gray) have recently received increasing attention. The nPGI nucleus likely plays an inhibitory role in ejaculation as evidenced through the urethrogenital reflex experimental model, a rat model for the expulsion phase of ejaculation (73, 74). Using the same model, the periaqueductal gray was found to be important for the ejaculation process, likely by acting as a relay between MPOA and nPGI (75). Midbrain structures have a significant role in ejaculation; however, much is still unknown about their exact role and further research is needed. summarizes the putative brain structures involved in ejaculation.

Putative brain structures involved in ejaculation. BNSTpm = posteromedial bed nucleus of stria terminalis; MeApd = posterodorsal medial amygdaloid nucleus; MPOA = medial preoptic area; PAG = periaqueductal gray; nPGi = paragigantocellular nucleus; PNpd = posterodorsal preoptic nucleus; PVN = paraventricular thalamic nucleus; SPFp = parvicellular part of the subparafascicular thalamus. (Reprinted with permission from Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, Rosen RC, eds. Cancer and sexual health. New York: Springer; 2011:82.)

NEUROCHEMICAL REGULATION OF EJACULATION

Many neurotransmitters are involved in the ejaculation process. Defining the exact role of these neurotransmitters is difficult given the variety of sexual parameters affected, the different sites of action within the spinal and the supraspinal pathways, and the presence of multiple receptor types. Some of the molecules that received special attention for their role in ejaculation are mentioned later.

Dopaminergic Control

Dopamine is known to be important for normal male sexual response (76, 77). Two families of dopamine receptors exist, D1-like (D1 and D5 receptors) and D2-like (D2, D3, and D4 receptors) (46). In rats, D2-like receptors are known to stimulate ejaculation (78, 79), and trigger ejaculation even in anesthetized rats (80, 81). Systemic injection of the D3 receptor agonist 7-OH-DPAT has been shown to trigger ejaculation in rats without affecting arousal (82, 83). It also triggers ejaculation in anesthetized rats when injected directly into the cerebral ventricles or MPOA with the effect being specifically reversed by the D3, not the D2 antagonist (84, 85). The D3 receptor blockage has been shown to inhibit the expulsion phase of ejaculation and lengthen ejaculation latency in rats (86).

Serotonergic Control

Evidence suggests that serotonin (5HT) inhibits ejaculation (87). Selective serotonin reuptake inhibitors increase 5HT tone resulting in impairment of ejaculation, which led to their clinical use in premature ejaculation. This inhibitory effect is likely to occur in the brain (88), as 5HT effect on ejaculation in the spine is likely stimulatory (89). The amphetamine derivative p-chloroamphetamine leads to a sudden release of 5HT in synaptic clefts triggering ejaculation in anesthetized rats with complete spinal cord lesion (89). Intrathecal serotonin or selective serotonin reuptake inhibitor injection leads to enhancement of the expulsion phase of ejaculation (88). There are 14 receptor subtypes for 5HT, with 1A, 1B, and 2C being the ones involved in ejaculation (90). It is difficult to designate one influence for each receptor subtype, as each receptor could either activate or inhibit ejaculation depending on its location within the central nervous system (46).

Nitric Oxide

The role of NO in ejaculation has received special attention after the introduction of type-5 phosphodiesterase (PDE5) inhibitors and using them for premature ejaculation. Nitric oxide has an inhibitory role on the ejaculation process (1). Centrally, intrathecal sildenafil results in elevation of NO and cyclic guanosine monophosphate levels in MPOA causing a decreased peripheral sympathetic tone and inhibition of ejaculation (91). N-Nitro-l-arginine methyl-ester injection, an NO synthase inhibitor, was shown to increase the number of seminal emissions and reduce latency to first seminal emission in rats (92). Peripherally, nitronergic innervation and NO synthase were found in the seminal vesicle, vas deferens, prostate, and urethra (93–97). Therefore, drugs such as PDE5 inhibitors or NO donors are associated with reduced seminal vesicle contraction and inhibit seminal emission (92). The administration of NO inhibitors, such as l-nitroarginine-methylester, diminishes human seminal vesicle contraction (98), inhibits vasal contraction in guinea pigs (99), and decreases latency to ejaculation in rats (100). Furthermore, reduced latency to emission was found in knockout mice for the gene encoding endothelial NO synthase compared with their wild-type counterparts (101).

HORMONAL REGULATION OF EJACULATION

Although male sexual function is heavily regulated by the hormonal system, there are few clinical studies performed to evaluate hormonal regulation of ejaculation, and the knowledge about hormonal effect on ejaculation is still lacking. We discuss some of the studies examining the effect of different hormones on ejaculation.

Oxytocin

Oxytocin is an oligopeptide synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland. Oxytocin serum level increases after male ejaculation to levels ranging from 20%–360% of normal levels before reaching baseline at 10 minutes after ejaculation (102). Pharmacologic oxytocin administration in humans and animals results in increased ejaculated spermatozoa (103), confirming that oxytocin has a role in male genital tract motility. It was specifically found to augment powerful epididymal contractions and sperm motility (104), an important effect blunted by pretreatment with the oxytocin antagonist (des Gly–Nh3d(Ch3)5–[d-Tyr2,Thr4] ornithine vasotocin) (105). Peripheral oxytocin receptors were found to be highly expressed in the epididymis and tunica albuginea (in smooth muscles more than epithelial cells), and to a lesser extent in the vas deferens and seminal vesicle (104). Oxytocin has a synergistic action on the epididymis with endothelin-1, where they augment epididymal contraction and propel spermatozoa forward (102, 106). Injection of oxytocin into the cerebral ventricles in male rats facilitated ejaculation by shortening the ejaculation latency and postejaculatory refractory periods (107), whereas these effects were curbed using the oxytocin receptor antagonist (d(Ch3)5–Tyr(Me)–[Orn8]vasotocin) injected into the cerebral ventricles (108). Despite these encouraging findings and some anecdotal evidence suggesting that intranasal oxytocin can facilitate orgasm in an anorgasmic male (109), a double-blind placebo-controlled clinical study (110) failed to demonstrate an effect of intranasal oxytocin on sexual behavior.

Prolactin

Hyperprolactinemia has a marked inhibitory effect on male sexual desire (111). A modest increase in serum PRL levels (15–20 ng/mL) has been detected in men after orgasm, and could be contributing to the after-orgasm refractory period (112). Some investigators have hypothesized that a low PRL level is a cause of premature ejaculation, where PRL levels were similarly low in those men with lifelong or acquired premature ejaculation (113). Further research is needed on this issue.

Thyroid Hormones

The relationship between thyroid hormonal abnormalities and ejaculatory dysfunction has been well documented (114–116). In rats, l-thyroxin administration has been shown to increase bulbospongiosus contractile activity and seminal vesicle contraction frequency (117). Clinically, the prevalence of suppressed TSH, which is a marker of hyperthyroidism, was found to be twofold higher in patients with premature ejaculation than in patients who reported normal ejaculatory timing (118). In the first prospective multicenter study (114) on the topic, half of hyperthyroidism patients had premature ejaculation, whereas only 15% reported this symptom after cure of their thyroid dysfunction. Another single-center prospective study by Cihan et al. (116) demonstrated a prevalence of 72% of premature ejaculation in hyperthyroidism, which was reduced after treatment. It also identified a positive correlation of TSH with intravaginal ejaculation latency time. Öztürk et al. (119) found similar results. However, Waldinger et al. (120) found no correlation between TSH and intravaginal ejaculation latency time in a cohort of Dutch men with lifelong premature ejaculation. A meta-analysis by Corona et al. (102) demonstrated a threefold increase of hyperthyroidism in patients with premature ejaculation compared with controls, a finding that was more pronounced in patients with acquired rather than lifelong premature ejaculation. They also showed an increase in intravaginal ejaculation latency time by 84.6 ± 34.2 seconds (P=.001) upon treatment of hyperthyroidism. These findings suggest that thyroid hormones do not only affect the ankle reflex, but also the ejaculatory reflex, and screening patients with ejaculatory dysfunction for thyroid hormone abnormalities is warranted (102).

Glucocorticoids

Cortisol (F) levels in several animal studies were found to be elevated during arousal and ejaculation (121–123). In horses and donkeys, F was elevated 30 minutes after ejaculation, with unknown significance of this finding (124, 125). In addition, F levels were sharply elevated after electroejaculation in several anesthetized animal studies (126, 127). In humans, however, there was no change in F levels whether during sexual stimulation or orgasm (128–131). Although hypercortisolism in men was associated with reduced libido, no effect was identified on orgasm or ejaculation (132). Replacement of F in Addison disease was associated with improvement in overall sexual function including orgasm (133). Data in humans are still too preliminary to draw final conclusions, and further research is needed.

Estrogens

Estradiol plays an important role in the regulation of the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid reabsorption, and sperm concentration (134, 135). This role in the epididymis is the reason for recommending Tamoxifen as a first-line treatment for idiopathic oligospermia by the World Health Organization (136). Finkelstein et al. (137) showed that E2 deficiency, along with androgen deficiency, contributes to decreased libido and erectile function.

Androgens

Testosterone, through its central and peripheral androgen receptors, has a well-known role on male sexual function, particularly on libido (138). Low T levels are associated with delayed ejaculation, whereas high levels were associated with premature ejaculation (102). This is likely because the emission phase of the ejaculation relies on the NO-PDE5 system, which is influenced by T (138, 139). Testosterone facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other areas in the central nervous system (140). Furthermore, pelvic floor muscles involved in ejaculation are androgen dependent (141). There are likely multiple mechanisms involved in T action and further research is needed to identify specific targets for treatment in the ejaculatory reflex. summarizes the neurochemical and hormonal regulation of ejaculation.

TABLE 2

Neurochemical and hormonal regulation of ejaculation.

Neurotransmitter/hormone Effect
Dopamine Stimulates ejaculation through D2-like receptors (D2, D3, and D4 receptors, mainly D3)
Serotonin Inhibits ejaculation in the brain and stimulates it in the spine through the receptors 5HT, with 1A, 1B, and 2C
Nitric oxide Inhibits ejaculation through reduction of seminal vesicle contraction and seminal emission
Oxytocin Synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland
Augments powerful epididymal contractions and sperm motility
Acts in the CNS to stimulate ejaculation
Prolactin Secreted from the pituitary gland
Hyperprolactinemia has a marked inhibitory effect on male sexual desire, through inhibition of GnRH
 (therefore T production) and dopamine production
Thyroid hormones Hypothyroidism and hyperthyroidism are associated with delayed and premature ejaculation, respectively
Glucocorticoids Cortisol levels are elevated after ejaculation in animal studies
No change in cortisol levels in humans
Replacement of cortisol in Addison disease improves sexual function including orgasm
Estrogens Regulates the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid
 reabsorption, and sperm concentration
Androgens Low levels are associated with delayed ejaculation, whereas high levels are associated with premature ejaculation
Facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other
 areas in the CNS
Pelvic floor muscles involved in ejaculation are androgen dependent

In conclusion, ejaculation is a complex process involving several anatomical structures and under extensive neurochemical and hormonal regulation. Orgasm, although associated with ejaculation, is a distinct physiological process, different from ejaculation. Many aspects of these physiological processes are still unknown and further research is needed to identify treatments for ejaculatory dysfunction.

Footnotes

A.A. has nothing to disclose. B.N.B. has nothing to disclose. T.F.L. has nothing to disclose.

REFERENCES

1. Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, editors. Men’s sexual health and fertility. Springer Science; New York: 2014. pp. 13–29. [Google Scholar]2. Bella AJ, Shamloul R. Functional anatomy of the male sex organs. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 3–12. [Google Scholar]3. Meacham R, Lipshultz L, Howards S. Male infertility. In: Gillenwater JY, Grayhack JT, Howards S, Duckett JW, editors. Adult and pediatric urology. Mosby; St. Louis: 1996. pp. 1747–802. [Google Scholar]4. Hinman F. Normal surgical anatomy. In: Thomas Thomas AJ, Nagler HN, editors. Atlas of surgical management of male infertility. William & Wilkins; New York: 1995. pp. 9–20. [Google Scholar]5. Romanes G. The pelvis and perineum. In: Romanes G, Cunningham D, editors. Cunningham’s manual of practical anatomy. 13th ed Oxford University Press; London, UK: 1975. pp. 199–240. [Google Scholar]6. Tang Y, Rampin O, Calas A, Facchinetti P, Giuliano F. Oxytocinergic and serotonergic innervation of identified lumbosacral nuclei controlling penile erection in the male rat. Neuroscience. 1998;82:241–54. [PubMed] [Google Scholar]7. Danjou P, Lacomblez L, Warot D, Puech AJ. Assessment of erectogenic drugs by numeric plethysmography. J Pharmacol Methods. 1989;21:61–9. [PubMed] [Google Scholar]8. Clark JT, Smith ER, Davidson JM. Testosterone is not required for the enhancement of sexual motivation by yohimbine. Physiol Behav. 1985;35:517–21. [PubMed] [Google Scholar]9. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63:811–59. [PubMed] [Google Scholar]10. Lue TF, Zeineh SJ, Schmidt RA, Tanagho EA. Neuroanatomy of penile erection: its relevance to iatrogenic impotence. J Urol. 1984;131:273–80. [PubMed] [Google Scholar]11. Paick JS, Lee SW. The neural mechanism of apomorphine-induced erection: an experimental study by comparison with electrostimulation-induced erection in the rat model. J Urol. 1994;152(6 Pt 1):2125–8. [PubMed] [Google Scholar]12. Chapelle PA, Durand J, Lacert P. Penile erection following complete spinal cord injury in man. Br J Urol. 1980;52:216–9. [PubMed] [Google Scholar]14. Courtois FJ, Charvier KF, Leriche A, Raymond DP. Sexual function in spinal cord injury men. I. Assessing sexual capability. Paraplegia. 1993;31:771–84. [PubMed] [Google Scholar]15. Sattar AA, Salpigidis G, Schulman CC, Wespes E. Relationship between intrapenile O2 lever and quantity of intracavernous smooth muscle fibers: current physiopathological concept. Acta Urol Belg. 1995;63:53–9. [PubMed] [Google Scholar]16. Prieto D. Physiological regulation of penile arteries and veins. Int J Impot Res. 2007;20:17–29. [PubMed] [Google Scholar]17. Andersson KE. Pharmacology of penile erection. Pharmacol Rev. 2001;53:417–50. [PubMed] [Google Scholar]18. Walsh MP. The Ayerst Award Lecture 1990. Calcium-dependent mechanisms of regulation of smooth muscle contraction. Biochem Cell Biol. 1991;69:771–800. [PubMed] [Google Scholar]19. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci. 2002;99:4061–6. [PMC free article] [PubMed] [Google Scholar]20. Levin R. Physiology of orgasm. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 35–48. [Google Scholar]21. Masters W, Johnson V. Human sexual response. Little Brown; Boston: 1966. [Google Scholar]22. Levin R, editor. Heart rate responses can be used to differentiate simulated from real orgasms in the human male: a pilot study. Proceedings of the first conference on orgasm. VRP Publishers; Bombay: 1991. [Google Scholar]23. Gerstenberg TC, Levin RJ, Wagner G. Erection and ejaculation in man—assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles. Br J Urol. 1990;65:395–402. [PubMed] [Google Scholar]24. Levin R. Is prolactin the biological ‘off switch’ for human sexual arousal? Sex Relat Ther. 2003;18:289–343. [Google Scholar]25. Holstege G, Georgiadis JR, Paans AM, Meiners LC, van der Graaf FH, Reinders AS. Brain activation during human ejaculation. J Neurosci. 2003;23:9185–93. [PMC free article] [PubMed] [Google Scholar]26. Hite S. The Hite report on male sexuality. Ballantine Books; New York: 1981. [Google Scholar]27. Perry JF. Do men have a G-spot? Aust Forum. 1988;2:37–41. [Google Scholar]28. Levin R. Revisiting post-ejaculatory refractory time—what we know and what we do not know in males and females. J Sex Med. 2009;6:2376–89. [PubMed] [Google Scholar]29. Turley KR, Rowland DL. Evolving ideas about the male refractory period. BJU Int. 2013;112:442–52. [PubMed] [Google Scholar]30. Giuliano F, Clement P. Physiology of ejaculation: emphasis on serotonergic control. Eur Urol. 2005;48:408–17. [PubMed] [Google Scholar]31. Master VA, Turek PJ. Ejaculatory physiology and dysfunction. Urol Clin North Am. 2001;28:363–75. [PubMed] [Google Scholar]32. Schlegel PN, Walsh PC. Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol. 1987;16:46–60. [PubMed] [Google Scholar]33. Keast JR. Pelvic ganglia. In: McLahlan EM, editor. Autonomic ganglia. Harwood Academic; Luxemberg: 1995. pp. 445–79. [Google Scholar]34. Dail WG, Moll MA. Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat. Neuroscience. 1983;10:1379–86. [PubMed] [Google Scholar]35. Brindley GS, Sauerwein D, Hendry WF. Hypogastric plexus stimulators for obtaining semen from paraplegic men. Br J Urol. 1989;64:72–7. [PubMed] [Google Scholar]36. Ver Voort SM. Ejaculatory stimulation in spinal-cord injured men. Urology. 1987;29:282–9. [PubMed] [Google Scholar]37. Comarr A. Sexual function among patients with spinal cord injury. Urol Int. 1970;25:134–68. [PubMed] [Google Scholar]38. McKenna KE, Chung SK, McVary KT. A model for the study of sexual function in anesthetized male and female rats. Am J Physiol. 1991;261:R1276–85. [PubMed] [Google Scholar]39. Bergman B, Nilsson S, Petersen I. The effect on erection and orgasm of cystectomy, prostatectomy and vesiculectomy for cancer of the bladder: a clinical and electromyographic study. Br J Urol. 1979;51:114–20. [PubMed] [Google Scholar]40. Holmes GM, Sachs BD. The ejaculatory reflex in copulating rats: normal bulbospongiosus activity without apparent urethral stimulation. Neurosci Lett. 1991;125:195–7. [PubMed] [Google Scholar]41. Truitt WA, Coolen LM. Identification of a potential ejaculation generator in the spinal cord. Science. 2002;297:1566–9. [PubMed] [Google Scholar]42. Nunez R, Gross GH, Sachs BD. Origin and central projections of rat dorsal penile nerve: possible direct projection to autonomic and somatic neurons by primary afferents of nonmuscle origin. J Comp Neurol. 1986;247:417–29. [PubMed] [Google Scholar]43. Halata Z, Munger BL. The neuroanatomical basis for the protopathic sensibility of the human glans penis. Brain Res. 1986;371:205–30. [PubMed] [Google Scholar]44. Baron R, Janig W. Afferent and sympathetic neurons projecting into lumbar visceral nerves of the male rat. J Comp Neurol. 1991;314:429–36. [PubMed] [Google Scholar]45. McKenna KE, Nadelhaft I. The organization of the pudendal nerve in the male and female rat. J Comp Neurol. 1986;248:532–49. [PubMed] [Google Scholar]46. Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 77–89. [Google Scholar]47. Morgan C, de Groat WC, Nadelhaft I. The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat. J Comp Neurol. 1986;243:23–40. [PubMed] [Google Scholar]48. Owman C, Stjernquist M. The peripheral nervous system. In: Bjorklund A, Hokfelt T, Owman C, editors. Handbook of chemical neuroanatomy. Elsevier Science; Amsterdam, The Netherlands: 1988. pp. 445–544. [Google Scholar]49. Nadelhaft I, Booth AM. The location and morphology of preganglionic neurons and the distribution of visceral afferents from the rat pelvic nerve: a horseradish peroxidase study. J Comp Neurol. 1984;226:238–45. [PubMed] [Google Scholar]50. Schroder HD. Anatomical and pathoanatomical studies on the spinal efferent systems innervating pelvic structures. 1. Organization of spinal nuclei in animals. 2. The nucleus X-pelvic motor system in man. J Auton Nerv Syst. 1985;14:23–48. [PubMed] [Google Scholar]51. Coolen LM, Veening JG, Wells AB, Shipley MT. Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: evidence for functional subdivisions. J Comp Neurol. 2003;463:132–56. [PubMed] [Google Scholar]52. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Ejaculation elicited by microstimulation of lumbar spinothalamic neurons. Eur Urol. 2008;54:449–56. [PubMed] [Google Scholar]53. Hamson DK, Watson NV. Regional brainstem expression of Fos associated with sexual behavior in male rats. Brain Res. 2004;1006:233–40. [PubMed] [Google Scholar]54. Heeb MM, Yahr P. Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation. J Comp Neurol. 2001;439:248–58. [PubMed] [Google Scholar]55. Coolen LM, Peters HJ, Veening JG. Anatomical interrelationships of the medial preoptic area and other brain regions activated following male sexual behavior: a combined fos and tract-tracing study. J Comp Neurol. 1998;397:421–35. [PubMed] [Google Scholar]56. Kollack-Walker S, Newman SW. Mating-induced expression of c-fos in the male Syrian hamster brain: role of experience, pheromones, and ejaculations. J Neurobiol. 1997;32:481–501. [PubMed] [Google Scholar]57. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Demonstration of ejaculation-induced neural activity in the male rat brain using 5-HT1A agonist 8-OH-DPAT. Physiol Behav. 1997;62:881–91. [PubMed] [Google Scholar]58. Meisel R, Sachs B. The physiology of male sexual behavior. In: Knobil E, Neill J, editors. The physiology of reproduction. Raven; New York: 1994. pp. 3–105. [Google Scholar]59. Pehek EA, Thompson JT, Hull EM. The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res. 1989;500:325–32. [PubMed] [Google Scholar]60. Hull EM, Eaton RC, Markowski VP, Moses J, Lumley LA, Loucks JA. Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation. Life Sci. 1992;51:1705–13. [PubMed] [Google Scholar]61. Marson L, McKenna KE. Stimulation of the hypothalamus initiates the urethrogenital reflex in male rats. Brain Res. 1994;638:103–8. [PubMed] [Google Scholar]62. Larsson K, van Dis H. Seminal discharge following intracranial electrical stimulation. Brain Res. 1970;23:381–6. [PubMed] [Google Scholar]63. Arendash GW, Gorski RA. Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats. Brain Res Bull. 1983;10:147–54. [PubMed] [Google Scholar]64. Simerly RB, Swanson LW. Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol. 1988;270:209–42. [PubMed] [Google Scholar]65. Rizvi TA, Ennis M, Shipley MT. Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: A WGA-HRP and PHA-L study. J Comp Neurol. 1992;315:1–15. [PubMed] [Google Scholar]66. Murphy AZ, Rizvi TA, Ennis M, Shipley MT. The organization of preoptic medullary circuits in the male rat: evidence for interconnectivity of neural structures involved in reproductive behavior, antinociception and cardiovascular regulation. Neuroscience. 1999;91:1103–16. [PubMed] [Google Scholar]67. Saper CB, Loewy AD, Swanson LW, Cowan WM. Direct hypothalamo-autonomic connections. Brain Res. 1976;117:305–12. [PubMed] [Google Scholar]68. Luiten PG, Ter Horst GJ, Karst H, Steffens AB. The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res. 1985;329:374–8. [PubMed] [Google Scholar]69. Bancila M, Verge D, Rampin O, Backstrom JR, Sanders-Bush E, McKenna KE, et al. 5-Hydroxytryptamine2C receptors on spinal neurons controlling penile erection in the rat. Neuroscience. 1999;92:1523–37. [PubMed] [Google Scholar]70. Ackerman AE, Lange GM, Clemens LG. Effects of paraventricular lesions on sex behavior and seminal emission in male rats. Physiol Behav. 1997;63:49–53. [PubMed] [Google Scholar]71. Yasui Y, Saper CB, Cechetto DF. Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat. J Comp Neurol. 1991;308:293–310. [PubMed] [Google Scholar]72. Canteras NS, Simerly RB, Swanson LW. Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat. J Comp Neurol. 1995;360:213–45. [PubMed] [Google Scholar]73. Marson L, McKenna KE. A role for 5-hydroxytryptamine in descending inhibition of spinal sexual reflexes. Exp Brain Res. 1990;88:313–20. [PubMed] [Google Scholar]74. Marson L, McKenna KE. The identification of a brainstem site controlling spinal sexual reflexes in male rats. Brain Res. 1990;515:303–8. [PubMed] [Google Scholar]75. Marson L. Lesions of the periaqueductal gray block the medial preoptic area-induced activation of the urethrogenital reflex in male rats. Neurosci Lett. 2004;367:278–82. [PubMed] [Google Scholar]76. Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: influences on male sexual behavior. Physiol Behav. 2004;83:291–307. [PubMed] [Google Scholar]77. Peeters M, Giuliano F. Central neurophysiology and dopaminergic control of ejaculation. Neurosci Biobehav Rev. 2007;32:438–53. [PubMed] [Google Scholar]78. Ferrari F, Giuliani D. The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat. Life Sci. 1994;55:1155–62. [PubMed] [Google Scholar]79. Ferrari F, Giuliani D. Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919. Pharmacol Biochem Behav. 1995;50:29–34. [PubMed] [Google Scholar]80. Clément P, Bernabé J, Kia HK, Alexandre L, Giuliano F. D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino) tetralin in rats. J Pharmacol Exp Ther. 2006;316:830–4. [PubMed] [Google Scholar]81. Stafford SA, Coote JH. Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats. Br J Pharmacol. 2006;148:510–6. [PMC free article] [PubMed] [Google Scholar]82. Ferrari F, Giuliani D. Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats. Neuropharmacology. 1996;35:279–84. [PubMed] [Google Scholar]83. Ahlenius S, Larsson K. Effects of the dopamine D3 receptor ligand 7-OH-DPAT on male rat ejaculatory behavior. Pharmacol Biochem Behav. 1995;51:545–7. [PubMed] [Google Scholar]84. Clement P, Bernabe J, Denys P, Alexandre L, Giuliano F. Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats. Neuroscience. 2007;145:605–10. [PubMed] [Google Scholar]85. Kitrey ND, Clément P, Bernabé J, Alexandre L, Giuliano F. Microinjection of the preferential dopamine receptor D3 agonist 7-OH-DPAT into the hypothalamic medial preoptic area induced ejaculation in anesthetized rats. Neuroscience. 2007;149:636–41. [PubMed] [Google Scholar]86. Clément P, Pozzato C, Heidbreder C, Alexandre L, Giuliano F, Melotto S. Delay of ejaculation induced by SB-277011, a selective dopamine D3 receptor antagonist, in the rat. J Sex Med. 2009;6:98–108. [PubMed] [Google Scholar]87. Giuliano F. 5-hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention. Trends Neurosci. 2007;30:79–84. [PubMed] [Google Scholar]88. Clément P, Bernabé J, Gengo P, Denys P, Laurin M, Alexandre L, et al. Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine. Eur Urol. 2007;51:825–32. [PubMed] [Google Scholar]89. Stafford SA, Bowery NG, Tang K, Coote JH. Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats. Neuroscience. 2006;140:1031–40. [PubMed] [Google Scholar]90. Giuliano F, Clement P. Serotonin and premature ejaculation: from physiology to patient management. Eur Urol. 2006;50:454–66. [PubMed] [Google Scholar]91. Sato Y, Zhao W, Christ GJ. Central modulation of the NO/cGMP pathway affects the MPOAinduced intracavernous pressure response. Am J Physiol Regul Integr Com Physiol. 2001;281:R269–78. [PubMed] [Google Scholar]92. Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS. The roles of nitric oxide in sexual function of male rats. Neuropharmacology. 1994;33:1499–504. [PubMed] [Google Scholar]93. Dixon JS, Jen PY. Development of nerves containing nitric oxide synthase in the human male urogenital organs. Br J Urol. 1995;76:719–25. [PubMed] [Google Scholar]94. Hedlund P, Ekström P, Larsson B, Alm P, Andersson KE. Heme oxygen-ase and NO-synthase in the human prostate—relation to adrenergic, cholinergic and peptide-containing nerves. J Auton Nerv Syst. 1997;63:115–26. [PubMed] [Google Scholar]95. Jen PY, Dixon JS, Gosling JA. Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase in nerves supplying the human postnatal vas deferens and seminal vesicle. Br J Urol. 1997;80:291–9. [PubMed] [Google Scholar]96. Kaminski HJ, Andrade FH. Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord. 2001;11:517–24. [PubMed] [Google Scholar]97. Ückert S, Bazrafshan S, Scheller F, Mayer ME, Jonas U, Stief CG. Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors. Urology. 2007;70:185–9. [PubMed] [Google Scholar]98. Bultmann R, Klebroff W, Starke K. Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. Eur J Pharmacol. 2002;436:135–43. [PubMed] [Google Scholar]99. Kato K, Furuya K, Tsutsui I, Ozaki T, Yamagishi S. Cyclic AMP-mediated inhibition of noradrenaline-induced contraction and Ca2+ in flux in guinea-pig vas deferens. Exp Physiol. 2000;85:387–98. [PubMed] [Google Scholar]100. Bialy M, Beck J, Abramczyk P, Trzebskj A, Przybylski J. Sexual behavior in male rats after nitric oxide synthesis inhibition. Physiol Behav. 1996;60:139–43. [PubMed] [Google Scholar]101. Kriegsfeld LJ, Demas GE, Huang PL, Burnett AL, Nelson RJ. Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS) Physiol Behav. 1999;67:561–6. [PubMed] [Google Scholar]102. Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9:508–19. [PubMed] [Google Scholar]103. Maggi M, Kassis S, Malozowski S. Identification and characterization of a vasopressin isoreceptor in porcine seminal vesicles. Proc Natl Acad Sci. 1986;83:8824–8. [PMC free article] [PubMed] [Google Scholar]104. Filippi S, Vannelli GB, Granchi S. Identification, localization and functional activity of oxytocin receptors in epididymis. Mol Cell Endocrinol. 2002;193:89–100. [PubMed] [Google Scholar]105. Nicholson HD, Parkinson TJ, Lapwood KR. Effects of oxytocin and vasopressin on sperm transport from the cauda epididymis in sheep. J Reprod Fertil. 1999;117:299–305. [PubMed] [Google Scholar]106. Einspanier A, Ivell R. Oxytocin and oxytocin receptor expression in reproductive tissues of the male marmoset monkey. Biol Reprod. 1997;56:416–22. [PubMed] [Google Scholar]107. Arletti R, Bazzani C, Castelli M. Oxytocin improves male copulatory performance in rats. Horm Bev. 1985;19:14–20. [PubMed] [Google Scholar]108. Argiolas A, Collu M, d’Aquila P, Gessa GL, Melis MR, Serra G. Apomorphine stimulation of male copulatory behavior is prevented by the oxytocin antagonist d(Ch3)5Tyr(Me)-Orn8-vasotocin in rats. Pharmacol Biochem Behav. 1988;33:81–3. [PubMed] [Google Scholar]109. Ishak WW, Berman DS, Peters A. Male anorgasmia treated with oxytocin. J Sex Med. 2008;5:1022–4. [PubMed] [Google Scholar]110. Burri A, Heinrichs M, Schedlowski M, Kruger TH. The acute effects of intra-nasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008;33:591–600. [PubMed] [Google Scholar]111. Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15:373–7. [PubMed] [Google Scholar]112. Exton MS, Krüger TH, Koch M, Paulson E, Knapp W, Hartmann U, et al. Coitus-induced orgasm stimulates prolactin secretion in healthy subjects. Psychoneuroendocrinology. 2001;26:31–44. [PubMed] [Google Scholar]113. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, et al. Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction. J Sex Med. 2009;6:1457–66. [PubMed] [Google Scholar]114. Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005;90:6472–9. [PubMed] [Google Scholar]115. Corona G, Mannucci E, Petrone L, Fisher AD, Balercia G, Scisciolo G, et al. Psychobiological correlates of delayed ejaculation in male patients with sexual dysfunctions. J Androl. 2006;27:453–8. [PubMed] [Google Scholar]116. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. The relationship between premature ejaculation and hyperthyroidism. J Urol. 2009;181:1273–80. [PubMed] [Google Scholar]117. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. Investigation of the neural target level of hyperthyroidism in premature ejaculation in a rat model of pharmacologically induced ejaculation. J Sex Med. 2011;8:90–6. [PubMed] [Google Scholar]118. Corona G, Ricca V, Bandini E, Rastrelli G, Casale H, Jannini E, et al. SIEDY Scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction. J Sex Med. 2012;9:2017–26. [PubMed] [Google Scholar]119. Öztürk MI, Koca O, Tüken M, Keleş MO, Ilktac A, Karaman MI. Hormonal evaluation in premature ejaculation. Urol Int. 2011;88:454–8. [PubMed] [Google Scholar]120. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH. Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction. J Sex Med. 2005;2:865–70. [PubMed] [Google Scholar]121. Rabb MH, Thompson DL, Barry BE, Colborn DR, Garza F, Hehnke KE. Effects of sexual stimulation, with and without ejaculation, on serum concentrations of, LH, FSH, testosterone, cortisol and prolactin in stallions. J Anim Sci. 1989;67:2724–9. [PubMed] [Google Scholar]122. Borg KE, Esbenshade KL, Johnson BH. Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar. J Anim Sci. 1991;69:3230–40. [PubMed] [Google Scholar]123. Bishop JD, Malven PV, Singleton WL, Weesner GD. Hormonal and behavioural correlates of emotional states in sexually trained boars. J Anim Sci. 1999;77:3339–45. [PubMed] [Google Scholar]124. Veronesi MC, Tosi U, Villani M, Govoni N, Faustini M, Kindahl H, et al. Oxytocin, vasopressin, prostaglandin F(2α), luteinizing hormone, testosterone, estrone sulfate, and cortisol plasma concentrations after sexual stimulation in stallions. Theriogenology. 2010;73:460–7. [PubMed] [Google Scholar]125. Veronesi MC, de Amicis I, Panzani S, Kindahl H, Govoni N, Probo M, et al. PGF(2α), LH, testosterone, oestrone sulphate, and cortisol plasma concentrations around sexual stimulation in jackass. Theriogenology. 2011;75:1489–98. [PubMed] [Google Scholar]126. Wildt DE, Phillips LG, Simmons LG, Chakraborty PK, Brown JL, Howard JG, et al. A comparative analysis of ejaculate and hormonal characteristics of the captive male cheetah, tiger, leopard, and puma. Biol Reprod. 1988;38:245–55. [PubMed] [Google Scholar]127. Brown JL, Wildt DE, Phillips LG, Seidensticker J, Fernando SB, Miththapala S, et al. Adrenal–pituitary–gonadal relationships and ejaculate characteristics in captive leopards (Panthera pardus kotiya) isolated on the island of Sri Lanka. J Reprod Fertil. 1989;85:605–13. [PubMed] [Google Scholar]128. Carani C, Bancroft J, Del Rio G, Granata ARM, Facchinetti F, Marrama P. The endocrine effects of visual erotic stimuli in normal men. Psychoneuroendocrinology. 1990;15:207–16. [PubMed] [Google Scholar]129. Krüger T, Exton MS, Pawlak C, von zur Mühlen A, Hartmann U, Schedlowski M. Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men. Psychoneuroendocrinology. 1998;23:401–11. [PubMed] [Google Scholar]130. Exton NG, Truong TC, Exton MS, Wingenfeld SA, Leygraf N, Saller B, et al. Neuroendocrine response to film-induced sexual arousal in men and women. Psychoneuroendocrinology. 2000;25:187–99. [PubMed] [Google Scholar]131. Ismail AA, Davidson DW, Loraine JA. Relationship between plasma cortisol and human sexual activity. Nature. 1972;237:288–9. [PubMed] [Google Scholar]132. Valassi E, Santos A, Yaneva M, Tóth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. J Endocrinol. 2011;165:383–92. [PubMed] [Google Scholar]133. Granata A, Tirabassi G, Pugni V, Arnaldi G, Boscaro M, Carani C, et al. Sexual dysfunctions in men affected by autoimmune addison’s disease before and after short-term gluco- and mineralocorticoid replacement therapy. J Sex Med. 2013;10:2036–43. [PubMed] [Google Scholar]134. Vignozzi L, Filippi S, Morelli A, Luconi M, Jannini E, Forti G, et al. Regulation of epididymal contractility during semen emission, the first part of the ejaculatory process: a role for estrogen. J Sex Med. 2008;5:2480. [PubMed] [Google Scholar]136. Rowe P, Comhaire F. WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge University Press; Cambridge: 2000. [Google Scholar]137. Finkelstein JS, Lee H, Burnett-Bowie SAM, Pallais JC, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22. [PMC free article] [PubMed] [Google Scholar]138. Corona G, Maggi M. The role of testosterone in erectile dysfunction. Nat Rev Urol. 2010;7:46–56. [PubMed] [Google Scholar]139. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004;145:2253–63. [PubMed] [Google Scholar]140. Swaab DF. Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab. 2007;21:431–44. [PubMed] [Google Scholar]

emphasis on orgasm and ejaculation

Fertil Steril. Author manuscript; available in PMC 2016 Jun 7.

Published in final edited form as:

PMCID: PMC4896089

NIHMSID: NIHMS789951

, M.D., M.Sc.,a,b, M.D., M.A.S.,b and , M.D.b

Amjad Alwaal

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Benjamin N. Breyer

bDepartment of Urology, University of California, San Francisco, California

Tom F. Lue

bDepartment of Urology, University of California, San Francisco, California

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Reprint requests: Amjad Alwaal, M.D., M.Sc., King Abdulaziz University, Department of Urology, P. O. Box 80215, Jeddah, Saudi Arabia 21589 ([email protected]).The publisher’s final edited version of this article is available at Fertil SterilSee other articles in PMC that cite the published article.

Abstract

Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process.

Keywords: Erectile function, male sexual function, ejaculation, orgasm

Ejaculatory dysfunction is one of the most common male sexual dysfunctions that is often mis-diagnosed or disregarded. At present, there is no definitive cure for ejaculatory dysfunctions (1). New research on the physiology of ejaculation keeps emerging to identify targets of treatment. However, knowledge about this topic is still lacking. In the present article, we summarize the current literature on the physiology of ejaculation. We describe the anatomy of the organs involved and the erection physiology. We discuss the physiology of orgasm and ejaculation as two separate physiological processes. In addition, we describe the neurochemical and hormonal regulation of the ejaculation process.

FUNCTIONAL ANATOMY OF THE MALE GENITAL ORGANS

The male genital system consists of external and internal reproductive and sexual organs such as the penis, prostate, epididymis, and testes. shows the gross anatomy of the ejaculatory structures. provides a summary of the functional anatomy of these organs (2–5).

Gross anatomy of the ejaculation structures. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:15.)

TABLE 1

Summary of the functional anatomy of the male genital organs.

Organ Characteristics
Penis Composed of three chambers: paired corpora cavernosa (erectile bodies) and a midline ventral corpus spongiosum
 (contains urethra)
Main blood supply: internal pudendal artery
Somatic sensation: pudendal nerve (S2-S4)
Autonomic nerve fibers: cavernous nerves (pelvic plexus) contain both sympathetic (hypogastric plexus) and
 parasympathetic nerve fibers (S2-S4)
Urethra Four segments: prostatic urethra, membranous urethra (passes through the urogenital diaphragm), bulbar urethra,
 and penile urethra (ends with a small dilatation at the fossa navicularis near the meatus)
Cowper’s glands: located on both sides of the membranous urethra and open in the bulbar urethra
Veromontanum: small elevation of the posterior wall of the membranous urethra, related to ejaculatory ducts, prostatic
 utricle, and prostatic ducts
Testis It is divided by fibrous septa into many lobules containing seminiferous tubules
Leydig cells: main source of T production
Seminiferous tubules: contain germ cells and sertoli cells. Forms the rete testis inside the testis mediastinum
Rete testis: gives rise to 15–20 efferent ductules
Epididymis Posterior and superior to the testicle
Composed of head, body, and tail
Efferent ductules unite to form the convoluted duct of the epididymis
Becomes the vas deferens at the end of the tail
Vas deferens Muscular tube; typically 45 cm long and has a 2.5 mm diameter
It is a continuation of the epididymis
Joins the seminal vesicle duct to form the ejaculatory duct, which then drains into the veromontanum
Supplied by the vasal artery, a branch of the inferior vesical artery
Prostate Surrounds the prostatic urethra
Composed of 70% glandular component and 30% fibromuscular component
Arterial supply: inferior vesical and middle rectal arteries
Seminal
 vesicles
Paired structures; located lateral to the vas deferens
Typically 5 cm long and 1 cm wide
Joins the vas to form the ejaculatory duct
Arterial supply: inferior vesical and middle rectal arteries

PHYSIOLOGY OF ERECTION

The penile erection results from complex neurovascular mechanisms. Several central and peripheral neurological factors in addition to molecular, vascular, psychological and endocrino-logical factors are involved, and the balance between these factors is what eventually determines the functionality of the penis. In this section, we summarize some of those mechanisms.

Cerebral Control

Cerebrally controlled penile erections are induced through erotic visual stimuli or thoughts. The main cerebral structures involved in erection are contained within the medial preoptic area (MPOA) and paraventricular nucleus (PVN) in the hypothalamus (6). Dopamine is the most important brain neurotransmitter for erection, likely through its stimulation of oxytocin release (7). Another important neurotransmitter is norepinephrine, which is demonstrated through the erectogenic effect of the α-2 agonist (Yohimbine) (8). Several other brain neurotransmitters are involved in the erection process to varying degrees such as nitric oxide (NO), α-melanocyte stimulating hormone (α-MSH), and opioid peptides (9).

Autonomic Control

Parasympathetic stimulation is the main mediator for penile tumescence, although central suppression of the sympathetic nervous system also plays a role. Parasympathetic supply to the penis is derived from the sacral segments S2-S4 (10). However, patients with sacral spinal cord injury still maintain erections through psychogenic stimulation, although of less rigidity than normal. These psychogenic erections do not occur in patients with lesions above T9 (11), suggesting that the main mechanism for these erections is central suppression of sympathetic stimulation (12). Patients with lesions above T9 still may maintain reflexogenic erections. This implies that the main mechanism for reflexogenic tumescence is the preservation of the sacral reflex arc, which mediates erection through tactile penile stimulation (13, 14).

Molecular Mechanisms

The penis at baseline is in a flaccid state maintained by the contraction of corporal smooth muscles and constriction of cavernous and helicine arteries leading to moderate state of hypoxia with partial pressure of oxygen of 30–40 mm Hg (15). During sexual arousal, NO is released from cavernous nerve terminals through the action of neuronal NO synthase (16). The NO activates guanylate cyclase, which in turn converts guanosine triphosphate to cyclic guanosine monophosphate (15, 17), leading eventually to smooth muscle relaxation and vasodilation (18). Although the initiation of tumescence is through neuronal NO synthase, the maintenance of erection is through endothelial NO synthase (19). The eventual smooth muscle relaxation and vasodilation results in blood flowing into the paired corpora and filling of the sinusoids, with increased intracorporal pressure (to >100 mm Hg during full erection) and compression of the subtunical venules, markedly reducing the venous outflow (13).

PHYSIOLOGY OF ORGASM

There is no standard definition of orgasm. Each specialty such as endocrinology or psychology examines this activity from each one’s perspective, making it difficult to reach a consensus on the definition. Orgasm is generally associated with ejaculation, although the two processes are physiologically different (20). Certain physiological features are associated with orgasm, including hyperventilation up to 40 breaths/min, tachycardia, and high blood pressure (21). In fact, faster heart rate was found to be an indicator of “real” male orgasm during intravaginal intercourse, differentiating it from “fake” orgasm (22). Orgasm is also associated with powerful and highly pleasurable pelvic muscle contractions (especially ischiocavernosus and bulbocavernosus) (23), along with rectal sphincter contractions and facial grimacing (21). There is also an associated release and elevation in PRL and oxytocin levels after orgasm; however, the significance of this elevation is not entirely clear (24).

Studies using positron emission tomography, which measures changes in regional cerebral blood flow, have identified areas of activation in the brain during orgasm. Primary intense activation areas are noted to be in the mesodiencephalic transition zones, which includes the midline, the zona incerta, ventroposterior and intralaminar thalamic nuclei, the lateral segmental central field, the suprafascicular nucleus, and the ventral tegmental area. Strong increases were seen in the cerebellum. Decreases were noted at the entorhinal cortex and the amygdale (25).

Quality and intensity of orgasms are variable. For instance, short fast buildup of sexual stimulation toward orgasm is associated with less intense orgasms than slow buildup. Early orgasms are less satisfying than later orgasms in life as the person learns to accept the pleasure associated with orgasms. Lower levels of androgen are associated with weaker orgasms, such as in hypogonadism or in older age (20). It has been suggested that pelvic muscle exercises, particularly the bulbocavernosus and ischiocavernosus muscles, through contracting those muscles 60 times, 3 times daily for 6 weeks will enhance the pleasure associated with orgasm (20). However, the effort and time associated with such exercises prevent their utilization. The orgasm induced through deep prostatic massage is thought to be different from the orgasm associated direct penile stimulation. Although penile stimulation orgasms are associated with 4–8 pelvic muscle contractions, prostatic massage orgasms are associated with 12 contractions. Prostatic massage orgasms are thought to be more intense and diffuse than penile stimulation orgasms, but they require time and practice and are not liked by many men (20, 26, 27).

Following orgasm in men is a temporary period of inhibition of erection or ejaculation called the refractory period. This is a poorly understood phenomenon, with some investigators suggesting a central rather than spinal mechanism causing it (28). Elevated levels of PRL and serotonin after orgasm have been suggested as a potential cause; however, there is much debate about their exact role (29). More research is still needed in the area of male orgasm (20).

PHYSIOLOGY OF EJACULATION

Ejaculation is a physiological process heavily controlled by the autonomic nervous system. It consists of two main phases: emission and expulsion. The main organs involved in ejaculation are the distal epididymis, the vas deferens, the seminal vesicle, the prostate, the prostatic urethra, and the bladder neck (30).

Emission

The first step in the emission phase is the closure of bladder neck to prevent retrograde spillage of the seminal fluid into the bladder. This is followed by the ejection of prostatic secretions (10% of the final semen volume) containing acid phosphatase, citric acid, and zinc, mixed with spermatozoa from the vas deferens (10% of the volume) into the prostatic urethra. Subsequently, the fructose-containing seminal vesicle fluid alkalinizes the final ejaculatory fluid. The seminal vesicle fluid constitutes 75%–80% of the final seminal fluid. Cowper’s glands and periurethral glands produce a minority of the seminal fluid (1, 31). The organs involved in the ejaculation process receive dense autonomic nerve supply, both sympathetic and parasympathetic, from the pelvic plexus. The pelvic plexus is located retroperitoneally on either side of the rectum, lateral and posterior to the seminal vesicle (32). It receives neuronal input from the hypogastric and pelvic nerves in addition to the caudal paravertebral sympathetic chain (33). The sympathetic neurons play the predominant role in the ejaculation process. Their nerve terminals secrete primarily norepinephrine, although other neurotransmitters such as acetylcholine and nonadrenergic/noncholinergic also play important roles (34). The role of the hypogastric plexus in emission is best demonstrated clinically by the loss of emission after non-nerve sparing para-aortic lymph node dissection for testicular cancer (35), and induction of emission in paraplegic men through electrical stimulation of superior hypogastric plexus (35). Input from genital stimulation is integrated at the neural sacral spinal level to produce emission (36). The emission phase of ejaculation is also under a considerable cerebral control, and can be induced through physical or visual erotic stimulation (37).

Expulsion

Expulsion follows emission as the process of ejaculation climaxes, and refers to the ejection of semen through the urethral meatus. The semen is propelled through the rhythmic contractions of the pelvic striated muscles in addition to the bulbospongiosus and ischiocavernosus muscles (23). To achieve antegrade semen expulsion, the bladder neck remains closed, whereas the external urethral sphincter is open. The external sphincter and the pelvic musculature are under somatic control; however, there is no evidence that voluntary control plays a role in the expulsion process (30). The exact trigger for expulsion is unknown. It has been suggested that a spinal center is triggered during emission of seminal fluid into the prostatic urethra (38). However, there is mounting evidence through clinical and experimental studies to suggest that this is not the case. For instance, men can still have rhythmic contractions during orgasm despite “dry ejaculation,” for example, due to prostatectomy (23, 39, 40). This, in addition to the identification of spinal generator for ejaculation (SGE) in rats, led to the postulation that the process of expulsion is a continuum of the process initiated through emission, after reaching a certain spinal activation threshold (30, 41).

NEURONAL CONTROL OF EJACULATION

Ejaculation is heavily controlled by the nervous system. summarizes the reflex circuit necessary to elicit ejaculation.

Reflex circuit needed to establish ejaculation. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:18.)

Peripheral Nervous System

Afferents

The main sensory input from the penis comes from the dorsal nerve of the penis, which transmits sensation from the glans, prepuce, and penile shaft. It transmits signals to the upper and lower segments of the sacral spinal cord (42). The glans contains encapsulated nerve endings, termed Krause-Finger corpuscles, whereas the remaining penile shaft contains free nerve endings. Stimulation of these corpuscles potentiated by stimulation from other genital areas, such the perineum, testes, and penile shaft, play an important role in the ejaculation process (43). A secondary afferent route is through the hypogastric nerve, which runs through the paravertebral sympathetic chain to enter the spinal cord through the thoracolumbar dorsal roots (44). The sensory afferents terminate in the medial dorsal horn and the dorsal gray commissure of the spinal cord (45).

Efferents

The efferent peripheral nervous system constitutes of sympathetic, parasympathetic, and motor nervous components (46). The soma of the preganglionic sympathetic cell bodies involved in ejaculation are located in the intermedio-lateral cell column and in the central autonomic region of the thoracolumbar segments (T12-L1) (47). The preganglionic sympathetic fibers emerge from the ventral roots of the spinal cord and travel through the paravertebral sympathetic chain to relay either directly through the splanchnic nerve, or through relaying first in the celiac superior mesenteric ganglia and then through the intermesenteric nerve, to the inferior mesenteric ganglia (48). The hypogastric nerve then emanates from the inferior mesenteric ganglia to join the parasympathetic pelvic nerve to form the pelvic plexus, which then sends fibers to the ejaculation structures (49). The preganglionic parasympathetic cell bodies are located in the sacral parasympathetic nucleus. The sacral parasympathetic nucleus neurons travel then in the pelvic nerve to the post-ganglionic parasympathetic cells located in the pelvic plexus. The motor neurons involved in ejaculation are located in Onuf’s nucleus in the sacral spinal cord, which projects fibers through the motor component of the pudendal nerve to reach the pelvic musculature, including the bulbospongiosus, ischiocavernosus, and external urethral sphincter (50).

Central Nervous System

Spinal network

The thoracolumbar sympathetic, sacral parasympathetic (mainly sacral parasympathetic nucleus), and somatic sacral Onuf’s nucleus ejaculatory spinal nuclei play an important role in the integration of peripheral and cerebral input and coordinating output to the pelviperineal structures involved in ejaculation (46). An additional spinal center is the SGE located in laminae X and VII of L3-L4 spinal segments (51). The SGE contains spinal interneurons called lumbar spinothalamic cells, which project fibers to the parvocellular subparafascicular nucleus of the thalamus in addition to preganglionic sympathetic and parasympathetic neurons innervating the pelvis (41). The SGE stimulation elicits a complete ejaculatory response resulting in collection of motile spermatozoa in anesthetized rats (52). Further research on the SGE spinal center is still needed, and it is unclear whether it contains other cells than lumbar spinothalamic cells.

Brain network

Sensory and motor areas in the brain play an important role in the ejaculation, which requires a highly coordinated and integrated central process. The study by Holstege et al. (25) using positron emission tomography showed that certain areas in the brain are activated in the orgasm and ejaculation process. Furthermore, specific areas in the brain have been involved in the ejaculation process, as demonstrated in animal immunohistochemical studies examining Fos protein pattern of expression (53–56), and confirmed using a serotonin 1A subtype receptor agonist proejaculatory pharmacologic agent in rats (57). These are discrete areas within the posteromedial bed nucleus of stria terminalis, the parvicellular part of the subparafascicular thalamus, the posterodorsal preoptic nucleus, and the posterodorsal medial amygdaloid nucleus. There are reciprocal connections that link those areas to the MPOA of the hypothalamus, a brain area with a well-established role in controlling sexual behavior as demonstrated by anatomical and functional studies (54, 55, 58). Electrical or chemical stimulation of the MPOA elicited ejaculation (59–62), whereas an MPOA lesion was shown to abolish both phases of ejaculation (63). No direct connections of MPOA to the spinal centers for ejaculation were found on neuroanatomical studies; however, there are projections of MPOA to other regions in the brain involved in ejaculation, such as PVN, the periaqueductal gray, and the paragigantocellular nucleus (nPGi) (64–66).

The PVN projects to pudendal motor neurons located in the L5-L6 spinal segment in addition to autonomic preganglionic neurons in the lumbosacral spinal cord in rats (45, 67, 68). It also projects to nPGI in the brainstem (69). Bilateral lesions of the PVN with N-methyl-D-aspartate (NMDA) results in a one-third reduction of the seminal ejaculate material weight (70). The parvicellular part of the subparafascicular thalamus was found to send projections to bed nucleus of stria terminalis, medial amygdala (MeA), and MPOA (71, 72) and receives input from lumbar spinothalamic cells (51). The precise role of these regions is still unclear but they are likely involved in relaying genital signals to MPOA (53, 55). The brainstem regions (nPGI and periaqueductal gray) have recently received increasing attention. The nPGI nucleus likely plays an inhibitory role in ejaculation as evidenced through the urethrogenital reflex experimental model, a rat model for the expulsion phase of ejaculation (73, 74). Using the same model, the periaqueductal gray was found to be important for the ejaculation process, likely by acting as a relay between MPOA and nPGI (75). Midbrain structures have a significant role in ejaculation; however, much is still unknown about their exact role and further research is needed. summarizes the putative brain structures involved in ejaculation.

Putative brain structures involved in ejaculation. BNSTpm = posteromedial bed nucleus of stria terminalis; MeApd = posterodorsal medial amygdaloid nucleus; MPOA = medial preoptic area; PAG = periaqueductal gray; nPGi = paragigantocellular nucleus; PNpd = posterodorsal preoptic nucleus; PVN = paraventricular thalamic nucleus; SPFp = parvicellular part of the subparafascicular thalamus. (Reprinted with permission from Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, Rosen RC, eds. Cancer and sexual health. New York: Springer; 2011:82.)

NEUROCHEMICAL REGULATION OF EJACULATION

Many neurotransmitters are involved in the ejaculation process. Defining the exact role of these neurotransmitters is difficult given the variety of sexual parameters affected, the different sites of action within the spinal and the supraspinal pathways, and the presence of multiple receptor types. Some of the molecules that received special attention for their role in ejaculation are mentioned later.

Dopaminergic Control

Dopamine is known to be important for normal male sexual response (76, 77). Two families of dopamine receptors exist, D1-like (D1 and D5 receptors) and D2-like (D2, D3, and D4 receptors) (46). In rats, D2-like receptors are known to stimulate ejaculation (78, 79), and trigger ejaculation even in anesthetized rats (80, 81). Systemic injection of the D3 receptor agonist 7-OH-DPAT has been shown to trigger ejaculation in rats without affecting arousal (82, 83). It also triggers ejaculation in anesthetized rats when injected directly into the cerebral ventricles or MPOA with the effect being specifically reversed by the D3, not the D2 antagonist (84, 85). The D3 receptor blockage has been shown to inhibit the expulsion phase of ejaculation and lengthen ejaculation latency in rats (86).

Serotonergic Control

Evidence suggests that serotonin (5HT) inhibits ejaculation (87). Selective serotonin reuptake inhibitors increase 5HT tone resulting in impairment of ejaculation, which led to their clinical use in premature ejaculation. This inhibitory effect is likely to occur in the brain (88), as 5HT effect on ejaculation in the spine is likely stimulatory (89). The amphetamine derivative p-chloroamphetamine leads to a sudden release of 5HT in synaptic clefts triggering ejaculation in anesthetized rats with complete spinal cord lesion (89). Intrathecal serotonin or selective serotonin reuptake inhibitor injection leads to enhancement of the expulsion phase of ejaculation (88). There are 14 receptor subtypes for 5HT, with 1A, 1B, and 2C being the ones involved in ejaculation (90). It is difficult to designate one influence for each receptor subtype, as each receptor could either activate or inhibit ejaculation depending on its location within the central nervous system (46).

Nitric Oxide

The role of NO in ejaculation has received special attention after the introduction of type-5 phosphodiesterase (PDE5) inhibitors and using them for premature ejaculation. Nitric oxide has an inhibitory role on the ejaculation process (1). Centrally, intrathecal sildenafil results in elevation of NO and cyclic guanosine monophosphate levels in MPOA causing a decreased peripheral sympathetic tone and inhibition of ejaculation (91). N-Nitro-l-arginine methyl-ester injection, an NO synthase inhibitor, was shown to increase the number of seminal emissions and reduce latency to first seminal emission in rats (92). Peripherally, nitronergic innervation and NO synthase were found in the seminal vesicle, vas deferens, prostate, and urethra (93–97). Therefore, drugs such as PDE5 inhibitors or NO donors are associated with reduced seminal vesicle contraction and inhibit seminal emission (92). The administration of NO inhibitors, such as l-nitroarginine-methylester, diminishes human seminal vesicle contraction (98), inhibits vasal contraction in guinea pigs (99), and decreases latency to ejaculation in rats (100). Furthermore, reduced latency to emission was found in knockout mice for the gene encoding endothelial NO synthase compared with their wild-type counterparts (101).

HORMONAL REGULATION OF EJACULATION

Although male sexual function is heavily regulated by the hormonal system, there are few clinical studies performed to evaluate hormonal regulation of ejaculation, and the knowledge about hormonal effect on ejaculation is still lacking. We discuss some of the studies examining the effect of different hormones on ejaculation.

Oxytocin

Oxytocin is an oligopeptide synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland. Oxytocin serum level increases after male ejaculation to levels ranging from 20%–360% of normal levels before reaching baseline at 10 minutes after ejaculation (102). Pharmacologic oxytocin administration in humans and animals results in increased ejaculated spermatozoa (103), confirming that oxytocin has a role in male genital tract motility. It was specifically found to augment powerful epididymal contractions and sperm motility (104), an important effect blunted by pretreatment with the oxytocin antagonist (des Gly–Nh3d(Ch3)5–[d-Tyr2,Thr4] ornithine vasotocin) (105). Peripheral oxytocin receptors were found to be highly expressed in the epididymis and tunica albuginea (in smooth muscles more than epithelial cells), and to a lesser extent in the vas deferens and seminal vesicle (104). Oxytocin has a synergistic action on the epididymis with endothelin-1, where they augment epididymal contraction and propel spermatozoa forward (102, 106). Injection of oxytocin into the cerebral ventricles in male rats facilitated ejaculation by shortening the ejaculation latency and postejaculatory refractory periods (107), whereas these effects were curbed using the oxytocin receptor antagonist (d(Ch3)5–Tyr(Me)–[Orn8]vasotocin) injected into the cerebral ventricles (108). Despite these encouraging findings and some anecdotal evidence suggesting that intranasal oxytocin can facilitate orgasm in an anorgasmic male (109), a double-blind placebo-controlled clinical study (110) failed to demonstrate an effect of intranasal oxytocin on sexual behavior.

Prolactin

Hyperprolactinemia has a marked inhibitory effect on male sexual desire (111). A modest increase in serum PRL levels (15–20 ng/mL) has been detected in men after orgasm, and could be contributing to the after-orgasm refractory period (112). Some investigators have hypothesized that a low PRL level is a cause of premature ejaculation, where PRL levels were similarly low in those men with lifelong or acquired premature ejaculation (113). Further research is needed on this issue.

Thyroid Hormones

The relationship between thyroid hormonal abnormalities and ejaculatory dysfunction has been well documented (114–116). In rats, l-thyroxin administration has been shown to increase bulbospongiosus contractile activity and seminal vesicle contraction frequency (117). Clinically, the prevalence of suppressed TSH, which is a marker of hyperthyroidism, was found to be twofold higher in patients with premature ejaculation than in patients who reported normal ejaculatory timing (118). In the first prospective multicenter study (114) on the topic, half of hyperthyroidism patients had premature ejaculation, whereas only 15% reported this symptom after cure of their thyroid dysfunction. Another single-center prospective study by Cihan et al. (116) demonstrated a prevalence of 72% of premature ejaculation in hyperthyroidism, which was reduced after treatment. It also identified a positive correlation of TSH with intravaginal ejaculation latency time. Öztürk et al. (119) found similar results. However, Waldinger et al. (120) found no correlation between TSH and intravaginal ejaculation latency time in a cohort of Dutch men with lifelong premature ejaculation. A meta-analysis by Corona et al. (102) demonstrated a threefold increase of hyperthyroidism in patients with premature ejaculation compared with controls, a finding that was more pronounced in patients with acquired rather than lifelong premature ejaculation. They also showed an increase in intravaginal ejaculation latency time by 84.6 ± 34.2 seconds (P=.001) upon treatment of hyperthyroidism. These findings suggest that thyroid hormones do not only affect the ankle reflex, but also the ejaculatory reflex, and screening patients with ejaculatory dysfunction for thyroid hormone abnormalities is warranted (102).

Glucocorticoids

Cortisol (F) levels in several animal studies were found to be elevated during arousal and ejaculation (121–123). In horses and donkeys, F was elevated 30 minutes after ejaculation, with unknown significance of this finding (124, 125). In addition, F levels were sharply elevated after electroejaculation in several anesthetized animal studies (126, 127). In humans, however, there was no change in F levels whether during sexual stimulation or orgasm (128–131). Although hypercortisolism in men was associated with reduced libido, no effect was identified on orgasm or ejaculation (132). Replacement of F in Addison disease was associated with improvement in overall sexual function including orgasm (133). Data in humans are still too preliminary to draw final conclusions, and further research is needed.

Estrogens

Estradiol plays an important role in the regulation of the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid reabsorption, and sperm concentration (134, 135). This role in the epididymis is the reason for recommending Tamoxifen as a first-line treatment for idiopathic oligospermia by the World Health Organization (136). Finkelstein et al. (137) showed that E2 deficiency, along with androgen deficiency, contributes to decreased libido and erectile function.

Androgens

Testosterone, through its central and peripheral androgen receptors, has a well-known role on male sexual function, particularly on libido (138). Low T levels are associated with delayed ejaculation, whereas high levels were associated with premature ejaculation (102). This is likely because the emission phase of the ejaculation relies on the NO-PDE5 system, which is influenced by T (138, 139). Testosterone facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other areas in the central nervous system (140). Furthermore, pelvic floor muscles involved in ejaculation are androgen dependent (141). There are likely multiple mechanisms involved in T action and further research is needed to identify specific targets for treatment in the ejaculatory reflex. summarizes the neurochemical and hormonal regulation of ejaculation.

TABLE 2

Neurochemical and hormonal regulation of ejaculation.

Neurotransmitter/hormone Effect
Dopamine Stimulates ejaculation through D2-like receptors (D2, D3, and D4 receptors, mainly D3)
Serotonin Inhibits ejaculation in the brain and stimulates it in the spine through the receptors 5HT, with 1A, 1B, and 2C
Nitric oxide Inhibits ejaculation through reduction of seminal vesicle contraction and seminal emission
Oxytocin Synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland
Augments powerful epididymal contractions and sperm motility
Acts in the CNS to stimulate ejaculation
Prolactin Secreted from the pituitary gland
Hyperprolactinemia has a marked inhibitory effect on male sexual desire, through inhibition of GnRH
 (therefore T production) and dopamine production
Thyroid hormones Hypothyroidism and hyperthyroidism are associated with delayed and premature ejaculation, respectively
Glucocorticoids Cortisol levels are elevated after ejaculation in animal studies
No change in cortisol levels in humans
Replacement of cortisol in Addison disease improves sexual function including orgasm
Estrogens Regulates the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid
 reabsorption, and sperm concentration
Androgens Low levels are associated with delayed ejaculation, whereas high levels are associated with premature ejaculation
Facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other
 areas in the CNS
Pelvic floor muscles involved in ejaculation are androgen dependent

In conclusion, ejaculation is a complex process involving several anatomical structures and under extensive neurochemical and hormonal regulation. Orgasm, although associated with ejaculation, is a distinct physiological process, different from ejaculation. Many aspects of these physiological processes are still unknown and further research is needed to identify treatments for ejaculatory dysfunction.

Footnotes

A.A. has nothing to disclose. B.N.B. has nothing to disclose. T.F.L. has nothing to disclose.

REFERENCES

1. Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, editors. Men’s sexual health and fertility. Springer Science; New York: 2014. pp. 13–29. [Google Scholar]2. Bella AJ, Shamloul R. Functional anatomy of the male sex organs. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 3–12. [Google Scholar]3. Meacham R, Lipshultz L, Howards S. Male infertility. In: Gillenwater JY, Grayhack JT, Howards S, Duckett JW, editors. Adult and pediatric urology. Mosby; St. Louis: 1996. pp. 1747–802. [Google Scholar]4. Hinman F. Normal surgical anatomy. In: Thomas Thomas AJ, Nagler HN, editors. Atlas of surgical management of male infertility. William & Wilkins; New York: 1995. pp. 9–20. [Google Scholar]5. Romanes G. The pelvis and perineum. In: Romanes G, Cunningham D, editors. Cunningham’s manual of practical anatomy. 13th ed Oxford University Press; London, UK: 1975. pp. 199–240. [Google Scholar]6. Tang Y, Rampin O, Calas A, Facchinetti P, Giuliano F. Oxytocinergic and serotonergic innervation of identified lumbosacral nuclei controlling penile erection in the male rat. Neuroscience. 1998;82:241–54. [PubMed] [Google Scholar]7. Danjou P, Lacomblez L, Warot D, Puech AJ. Assessment of erectogenic drugs by numeric plethysmography. J Pharmacol Methods. 1989;21:61–9. [PubMed] [Google Scholar]8. Clark JT, Smith ER, Davidson JM. Testosterone is not required for the enhancement of sexual motivation by yohimbine. Physiol Behav. 1985;35:517–21. [PubMed] [Google Scholar]9. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63:811–59. [PubMed] [Google Scholar]10. Lue TF, Zeineh SJ, Schmidt RA, Tanagho EA. Neuroanatomy of penile erection: its relevance to iatrogenic impotence. J Urol. 1984;131:273–80. [PubMed] [Google Scholar]11. Paick JS, Lee SW. The neural mechanism of apomorphine-induced erection: an experimental study by comparison with electrostimulation-induced erection in the rat model. J Urol. 1994;152(6 Pt 1):2125–8. [PubMed] [Google Scholar]12. Chapelle PA, Durand J, Lacert P. Penile erection following complete spinal cord injury in man. Br J Urol. 1980;52:216–9. [PubMed] [Google Scholar]14. Courtois FJ, Charvier KF, Leriche A, Raymond DP. Sexual function in spinal cord injury men. I. Assessing sexual capability. Paraplegia. 1993;31:771–84. [PubMed] [Google Scholar]15. Sattar AA, Salpigidis G, Schulman CC, Wespes E. Relationship between intrapenile O2 lever and quantity of intracavernous smooth muscle fibers: current physiopathological concept. Acta Urol Belg. 1995;63:53–9. [PubMed] [Google Scholar]16. Prieto D. Physiological regulation of penile arteries and veins. Int J Impot Res. 2007;20:17–29. [PubMed] [Google Scholar]17. Andersson KE. Pharmacology of penile erection. Pharmacol Rev. 2001;53:417–50. [PubMed] [Google Scholar]18. Walsh MP. The Ayerst Award Lecture 1990. Calcium-dependent mechanisms of regulation of smooth muscle contraction. Biochem Cell Biol. 1991;69:771–800. [PubMed] [Google Scholar]19. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci. 2002;99:4061–6. [PMC free article] [PubMed] [Google Scholar]20. Levin R. Physiology of orgasm. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 35–48. [Google Scholar]21. Masters W, Johnson V. Human sexual response. Little Brown; Boston: 1966. [Google Scholar]22. Levin R, editor. Heart rate responses can be used to differentiate simulated from real orgasms in the human male: a pilot study. Proceedings of the first conference on orgasm. VRP Publishers; Bombay: 1991. [Google Scholar]23. Gerstenberg TC, Levin RJ, Wagner G. Erection and ejaculation in man—assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles. Br J Urol. 1990;65:395–402. [PubMed] [Google Scholar]24. Levin R. Is prolactin the biological ‘off switch’ for human sexual arousal? Sex Relat Ther. 2003;18:289–343. [Google Scholar]25. Holstege G, Georgiadis JR, Paans AM, Meiners LC, van der Graaf FH, Reinders AS. Brain activation during human ejaculation. J Neurosci. 2003;23:9185–93. [PMC free article] [PubMed] [Google Scholar]26. Hite S. The Hite report on male sexuality. Ballantine Books; New York: 1981. [Google Scholar]27. Perry JF. Do men have a G-spot? Aust Forum. 1988;2:37–41. [Google Scholar]28. Levin R. Revisiting post-ejaculatory refractory time—what we know and what we do not know in males and females. J Sex Med. 2009;6:2376–89. [PubMed] [Google Scholar]29. Turley KR, Rowland DL. Evolving ideas about the male refractory period. BJU Int. 2013;112:442–52. [PubMed] [Google Scholar]30. Giuliano F, Clement P. Physiology of ejaculation: emphasis on serotonergic control. Eur Urol. 2005;48:408–17. [PubMed] [Google Scholar]31. Master VA, Turek PJ. Ejaculatory physiology and dysfunction. Urol Clin North Am. 2001;28:363–75. [PubMed] [Google Scholar]32. Schlegel PN, Walsh PC. Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol. 1987;16:46–60. [PubMed] [Google Scholar]33. Keast JR. Pelvic ganglia. In: McLahlan EM, editor. Autonomic ganglia. Harwood Academic; Luxemberg: 1995. pp. 445–79. [Google Scholar]34. Dail WG, Moll MA. Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat. Neuroscience. 1983;10:1379–86. [PubMed] [Google Scholar]35. Brindley GS, Sauerwein D, Hendry WF. Hypogastric plexus stimulators for obtaining semen from paraplegic men. Br J Urol. 1989;64:72–7. [PubMed] [Google Scholar]36. Ver Voort SM. Ejaculatory stimulation in spinal-cord injured men. Urology. 1987;29:282–9. [PubMed] [Google Scholar]37. Comarr A. Sexual function among patients with spinal cord injury. Urol Int. 1970;25:134–68. [PubMed] [Google Scholar]38. McKenna KE, Chung SK, McVary KT. A model for the study of sexual function in anesthetized male and female rats. Am J Physiol. 1991;261:R1276–85. [PubMed] [Google Scholar]39. Bergman B, Nilsson S, Petersen I. The effect on erection and orgasm of cystectomy, prostatectomy and vesiculectomy for cancer of the bladder: a clinical and electromyographic study. Br J Urol. 1979;51:114–20. [PubMed] [Google Scholar]40. Holmes GM, Sachs BD. The ejaculatory reflex in copulating rats: normal bulbospongiosus activity without apparent urethral stimulation. Neurosci Lett. 1991;125:195–7. [PubMed] [Google Scholar]41. Truitt WA, Coolen LM. Identification of a potential ejaculation generator in the spinal cord. Science. 2002;297:1566–9. [PubMed] [Google Scholar]42. Nunez R, Gross GH, Sachs BD. Origin and central projections of rat dorsal penile nerve: possible direct projection to autonomic and somatic neurons by primary afferents of nonmuscle origin. J Comp Neurol. 1986;247:417–29. [PubMed] [Google Scholar]43. Halata Z, Munger BL. The neuroanatomical basis for the protopathic sensibility of the human glans penis. Brain Res. 1986;371:205–30. [PubMed] [Google Scholar]44. Baron R, Janig W. Afferent and sympathetic neurons projecting into lumbar visceral nerves of the male rat. J Comp Neurol. 1991;314:429–36. [PubMed] [Google Scholar]45. McKenna KE, Nadelhaft I. The organization of the pudendal nerve in the male and female rat. J Comp Neurol. 1986;248:532–49. [PubMed] [Google Scholar]46. Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 77–89. [Google Scholar]47. Morgan C, de Groat WC, Nadelhaft I. The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat. J Comp Neurol. 1986;243:23–40. [PubMed] [Google Scholar]48. Owman C, Stjernquist M. The peripheral nervous system. In: Bjorklund A, Hokfelt T, Owman C, editors. Handbook of chemical neuroanatomy. Elsevier Science; Amsterdam, The Netherlands: 1988. pp. 445–544. [Google Scholar]49. Nadelhaft I, Booth AM. The location and morphology of preganglionic neurons and the distribution of visceral afferents from the rat pelvic nerve: a horseradish peroxidase study. J Comp Neurol. 1984;226:238–45. [PubMed] [Google Scholar]50. Schroder HD. Anatomical and pathoanatomical studies on the spinal efferent systems innervating pelvic structures. 1. Organization of spinal nuclei in animals. 2. The nucleus X-pelvic motor system in man. J Auton Nerv Syst. 1985;14:23–48. [PubMed] [Google Scholar]51. Coolen LM, Veening JG, Wells AB, Shipley MT. Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: evidence for functional subdivisions. J Comp Neurol. 2003;463:132–56. [PubMed] [Google Scholar]52. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Ejaculation elicited by microstimulation of lumbar spinothalamic neurons. Eur Urol. 2008;54:449–56. [PubMed] [Google Scholar]53. Hamson DK, Watson NV. Regional brainstem expression of Fos associated with sexual behavior in male rats. Brain Res. 2004;1006:233–40. [PubMed] [Google Scholar]54. Heeb MM, Yahr P. Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation. J Comp Neurol. 2001;439:248–58. [PubMed] [Google Scholar]55. Coolen LM, Peters HJ, Veening JG. Anatomical interrelationships of the medial preoptic area and other brain regions activated following male sexual behavior: a combined fos and tract-tracing study. J Comp Neurol. 1998;397:421–35. [PubMed] [Google Scholar]56. Kollack-Walker S, Newman SW. Mating-induced expression of c-fos in the male Syrian hamster brain: role of experience, pheromones, and ejaculations. J Neurobiol. 1997;32:481–501. [PubMed] [Google Scholar]57. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Demonstration of ejaculation-induced neural activity in the male rat brain using 5-HT1A agonist 8-OH-DPAT. Physiol Behav. 1997;62:881–91. [PubMed] [Google Scholar]58. Meisel R, Sachs B. The physiology of male sexual behavior. In: Knobil E, Neill J, editors. The physiology of reproduction. Raven; New York: 1994. pp. 3–105. [Google Scholar]59. Pehek EA, Thompson JT, Hull EM. The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res. 1989;500:325–32. [PubMed] [Google Scholar]60. Hull EM, Eaton RC, Markowski VP, Moses J, Lumley LA, Loucks JA. Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation. Life Sci. 1992;51:1705–13. [PubMed] [Google Scholar]61. Marson L, McKenna KE. Stimulation of the hypothalamus initiates the urethrogenital reflex in male rats. Brain Res. 1994;638:103–8. [PubMed] [Google Scholar]62. Larsson K, van Dis H. Seminal discharge following intracranial electrical stimulation. Brain Res. 1970;23:381–6. [PubMed] [Google Scholar]63. Arendash GW, Gorski RA. Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats. Brain Res Bull. 1983;10:147–54. [PubMed] [Google Scholar]64. Simerly RB, Swanson LW. Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol. 1988;270:209–42. [PubMed] [Google Scholar]65. Rizvi TA, Ennis M, Shipley MT. Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: A WGA-HRP and PHA-L study. J Comp Neurol. 1992;315:1–15. [PubMed] [Google Scholar]66. Murphy AZ, Rizvi TA, Ennis M, Shipley MT. The organization of preoptic medullary circuits in the male rat: evidence for interconnectivity of neural structures involved in reproductive behavior, antinociception and cardiovascular regulation. Neuroscience. 1999;91:1103–16. [PubMed] [Google Scholar]67. Saper CB, Loewy AD, Swanson LW, Cowan WM. Direct hypothalamo-autonomic connections. Brain Res. 1976;117:305–12. [PubMed] [Google Scholar]68. Luiten PG, Ter Horst GJ, Karst H, Steffens AB. The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res. 1985;329:374–8. [PubMed] [Google Scholar]69. Bancila M, Verge D, Rampin O, Backstrom JR, Sanders-Bush E, McKenna KE, et al. 5-Hydroxytryptamine2C receptors on spinal neurons controlling penile erection in the rat. Neuroscience. 1999;92:1523–37. [PubMed] [Google Scholar]70. Ackerman AE, Lange GM, Clemens LG. Effects of paraventricular lesions on sex behavior and seminal emission in male rats. Physiol Behav. 1997;63:49–53. [PubMed] [Google Scholar]71. Yasui Y, Saper CB, Cechetto DF. Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat. J Comp Neurol. 1991;308:293–310. [PubMed] [Google Scholar]72. Canteras NS, Simerly RB, Swanson LW. Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat. J Comp Neurol. 1995;360:213–45. [PubMed] [Google Scholar]73. Marson L, McKenna KE. A role for 5-hydroxytryptamine in descending inhibition of spinal sexual reflexes. Exp Brain Res. 1990;88:313–20. [PubMed] [Google Scholar]74. Marson L, McKenna KE. The identification of a brainstem site controlling spinal sexual reflexes in male rats. Brain Res. 1990;515:303–8. [PubMed] [Google Scholar]75. Marson L. Lesions of the periaqueductal gray block the medial preoptic area-induced activation of the urethrogenital reflex in male rats. Neurosci Lett. 2004;367:278–82. [PubMed] [Google Scholar]76. Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: influences on male sexual behavior. Physiol Behav. 2004;83:291–307. [PubMed] [Google Scholar]77. Peeters M, Giuliano F. Central neurophysiology and dopaminergic control of ejaculation. Neurosci Biobehav Rev. 2007;32:438–53. [PubMed] [Google Scholar]78. Ferrari F, Giuliani D. The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat. Life Sci. 1994;55:1155–62. [PubMed] [Google Scholar]79. Ferrari F, Giuliani D. Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919. Pharmacol Biochem Behav. 1995;50:29–34. [PubMed] [Google Scholar]80. Clément P, Bernabé J, Kia HK, Alexandre L, Giuliano F. D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino) tetralin in rats. J Pharmacol Exp Ther. 2006;316:830–4. [PubMed] [Google Scholar]81. Stafford SA, Coote JH. Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats. Br J Pharmacol. 2006;148:510–6. [PMC free article] [PubMed] [Google Scholar]82. Ferrari F, Giuliani D. Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats. Neuropharmacology. 1996;35:279–84. [PubMed] [Google Scholar]83. Ahlenius S, Larsson K. Effects of the dopamine D3 receptor ligand 7-OH-DPAT on male rat ejaculatory behavior. Pharmacol Biochem Behav. 1995;51:545–7. [PubMed] [Google Scholar]84. Clement P, Bernabe J, Denys P, Alexandre L, Giuliano F. Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats. Neuroscience. 2007;145:605–10. [PubMed] [Google Scholar]85. Kitrey ND, Clément P, Bernabé J, Alexandre L, Giuliano F. Microinjection of the preferential dopamine receptor D3 agonist 7-OH-DPAT into the hypothalamic medial preoptic area induced ejaculation in anesthetized rats. Neuroscience. 2007;149:636–41. [PubMed] [Google Scholar]86. Clément P, Pozzato C, Heidbreder C, Alexandre L, Giuliano F, Melotto S. Delay of ejaculation induced by SB-277011, a selective dopamine D3 receptor antagonist, in the rat. J Sex Med. 2009;6:98–108. [PubMed] [Google Scholar]87. Giuliano F. 5-hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention. Trends Neurosci. 2007;30:79–84. [PubMed] [Google Scholar]88. Clément P, Bernabé J, Gengo P, Denys P, Laurin M, Alexandre L, et al. Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine. Eur Urol. 2007;51:825–32. [PubMed] [Google Scholar]89. Stafford SA, Bowery NG, Tang K, Coote JH. Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats. Neuroscience. 2006;140:1031–40. [PubMed] [Google Scholar]90. Giuliano F, Clement P. Serotonin and premature ejaculation: from physiology to patient management. Eur Urol. 2006;50:454–66. [PubMed] [Google Scholar]91. Sato Y, Zhao W, Christ GJ. Central modulation of the NO/cGMP pathway affects the MPOAinduced intracavernous pressure response. Am J Physiol Regul Integr Com Physiol. 2001;281:R269–78. [PubMed] [Google Scholar]92. Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS. The roles of nitric oxide in sexual function of male rats. Neuropharmacology. 1994;33:1499–504. [PubMed] [Google Scholar]93. Dixon JS, Jen PY. Development of nerves containing nitric oxide synthase in the human male urogenital organs. Br J Urol. 1995;76:719–25. [PubMed] [Google Scholar]94. Hedlund P, Ekström P, Larsson B, Alm P, Andersson KE. Heme oxygen-ase and NO-synthase in the human prostate—relation to adrenergic, cholinergic and peptide-containing nerves. J Auton Nerv Syst. 1997;63:115–26. [PubMed] [Google Scholar]95. Jen PY, Dixon JS, Gosling JA. Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase in nerves supplying the human postnatal vas deferens and seminal vesicle. Br J Urol. 1997;80:291–9. [PubMed] [Google Scholar]96. Kaminski HJ, Andrade FH. Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord. 2001;11:517–24. [PubMed] [Google Scholar]97. Ückert S, Bazrafshan S, Scheller F, Mayer ME, Jonas U, Stief CG. Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors. Urology. 2007;70:185–9. [PubMed] [Google Scholar]98. Bultmann R, Klebroff W, Starke K. Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. Eur J Pharmacol. 2002;436:135–43. [PubMed] [Google Scholar]99. Kato K, Furuya K, Tsutsui I, Ozaki T, Yamagishi S. Cyclic AMP-mediated inhibition of noradrenaline-induced contraction and Ca2+ in flux in guinea-pig vas deferens. Exp Physiol. 2000;85:387–98. [PubMed] [Google Scholar]100. Bialy M, Beck J, Abramczyk P, Trzebskj A, Przybylski J. Sexual behavior in male rats after nitric oxide synthesis inhibition. Physiol Behav. 1996;60:139–43. [PubMed] [Google Scholar]101. Kriegsfeld LJ, Demas GE, Huang PL, Burnett AL, Nelson RJ. Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS) Physiol Behav. 1999;67:561–6. [PubMed] [Google Scholar]102. Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9:508–19. [PubMed] [Google Scholar]103. Maggi M, Kassis S, Malozowski S. Identification and characterization of a vasopressin isoreceptor in porcine seminal vesicles. Proc Natl Acad Sci. 1986;83:8824–8. [PMC free article] [PubMed] [Google Scholar]104. Filippi S, Vannelli GB, Granchi S. Identification, localization and functional activity of oxytocin receptors in epididymis. Mol Cell Endocrinol. 2002;193:89–100. [PubMed] [Google Scholar]105. Nicholson HD, Parkinson TJ, Lapwood KR. Effects of oxytocin and vasopressin on sperm transport from the cauda epididymis in sheep. J Reprod Fertil. 1999;117:299–305. [PubMed] [Google Scholar]106. Einspanier A, Ivell R. Oxytocin and oxytocin receptor expression in reproductive tissues of the male marmoset monkey. Biol Reprod. 1997;56:416–22. [PubMed] [Google Scholar]107. Arletti R, Bazzani C, Castelli M. Oxytocin improves male copulatory performance in rats. Horm Bev. 1985;19:14–20. [PubMed] [Google Scholar]108. Argiolas A, Collu M, d’Aquila P, Gessa GL, Melis MR, Serra G. Apomorphine stimulation of male copulatory behavior is prevented by the oxytocin antagonist d(Ch3)5Tyr(Me)-Orn8-vasotocin in rats. Pharmacol Biochem Behav. 1988;33:81–3. [PubMed] [Google Scholar]109. Ishak WW, Berman DS, Peters A. Male anorgasmia treated with oxytocin. J Sex Med. 2008;5:1022–4. [PubMed] [Google Scholar]110. Burri A, Heinrichs M, Schedlowski M, Kruger TH. The acute effects of intra-nasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008;33:591–600. [PubMed] [Google Scholar]111. Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15:373–7. [PubMed] [Google Scholar]112. Exton MS, Krüger TH, Koch M, Paulson E, Knapp W, Hartmann U, et al. Coitus-induced orgasm stimulates prolactin secretion in healthy subjects. Psychoneuroendocrinology. 2001;26:31–44. [PubMed] [Google Scholar]113. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, et al. Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction. J Sex Med. 2009;6:1457–66. [PubMed] [Google Scholar]114. Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005;90:6472–9. [PubMed] [Google Scholar]115. Corona G, Mannucci E, Petrone L, Fisher AD, Balercia G, Scisciolo G, et al. Psychobiological correlates of delayed ejaculation in male patients with sexual dysfunctions. J Androl. 2006;27:453–8. [PubMed] [Google Scholar]116. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. The relationship between premature ejaculation and hyperthyroidism. J Urol. 2009;181:1273–80. [PubMed] [Google Scholar]117. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. Investigation of the neural target level of hyperthyroidism in premature ejaculation in a rat model of pharmacologically induced ejaculation. J Sex Med. 2011;8:90–6. [PubMed] [Google Scholar]118. Corona G, Ricca V, Bandini E, Rastrelli G, Casale H, Jannini E, et al. SIEDY Scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction. J Sex Med. 2012;9:2017–26. [PubMed] [Google Scholar]119. Öztürk MI, Koca O, Tüken M, Keleş MO, Ilktac A, Karaman MI. Hormonal evaluation in premature ejaculation. Urol Int. 2011;88:454–8. [PubMed] [Google Scholar]120. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH. Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction. J Sex Med. 2005;2:865–70. [PubMed] [Google Scholar]121. Rabb MH, Thompson DL, Barry BE, Colborn DR, Garza F, Hehnke KE. Effects of sexual stimulation, with and without ejaculation, on serum concentrations of, LH, FSH, testosterone, cortisol and prolactin in stallions. J Anim Sci. 1989;67:2724–9. [PubMed] [Google Scholar]122. Borg KE, Esbenshade KL, Johnson BH. Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar. J Anim Sci. 1991;69:3230–40. [PubMed] [Google Scholar]123. Bishop JD, Malven PV, Singleton WL, Weesner GD. Hormonal and behavioural correlates of emotional states in sexually trained boars. J Anim Sci. 1999;77:3339–45. [PubMed] [Google Scholar]124. Veronesi MC, Tosi U, Villani M, Govoni N, Faustini M, Kindahl H, et al. Oxytocin, vasopressin, prostaglandin F(2α), luteinizing hormone, testosterone, estrone sulfate, and cortisol plasma concentrations after sexual stimulation in stallions. Theriogenology. 2010;73:460–7. [PubMed] [Google Scholar]125. Veronesi MC, de Amicis I, Panzani S, Kindahl H, Govoni N, Probo M, et al. PGF(2α), LH, testosterone, oestrone sulphate, and cortisol plasma concentrations around sexual stimulation in jackass. Theriogenology. 2011;75:1489–98. [PubMed] [Google Scholar]126. Wildt DE, Phillips LG, Simmons LG, Chakraborty PK, Brown JL, Howard JG, et al. A comparative analysis of ejaculate and hormonal characteristics of the captive male cheetah, tiger, leopard, and puma. Biol Reprod. 1988;38:245–55. [PubMed] [Google Scholar]127. Brown JL, Wildt DE, Phillips LG, Seidensticker J, Fernando SB, Miththapala S, et al. Adrenal–pituitary–gonadal relationships and ejaculate characteristics in captive leopards (Panthera pardus kotiya) isolated on the island of Sri Lanka. J Reprod Fertil. 1989;85:605–13. [PubMed] [Google Scholar]128. Carani C, Bancroft J, Del Rio G, Granata ARM, Facchinetti F, Marrama P. The endocrine effects of visual erotic stimuli in normal men. Psychoneuroendocrinology. 1990;15:207–16. [PubMed] [Google Scholar]129. Krüger T, Exton MS, Pawlak C, von zur Mühlen A, Hartmann U, Schedlowski M. Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men. Psychoneuroendocrinology. 1998;23:401–11. [PubMed] [Google Scholar]130. Exton NG, Truong TC, Exton MS, Wingenfeld SA, Leygraf N, Saller B, et al. Neuroendocrine response to film-induced sexual arousal in men and women. Psychoneuroendocrinology. 2000;25:187–99. [PubMed] [Google Scholar]131. Ismail AA, Davidson DW, Loraine JA. Relationship between plasma cortisol and human sexual activity. Nature. 1972;237:288–9. [PubMed] [Google Scholar]132. Valassi E, Santos A, Yaneva M, Tóth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. J Endocrinol. 2011;165:383–92. [PubMed] [Google Scholar]133. Granata A, Tirabassi G, Pugni V, Arnaldi G, Boscaro M, Carani C, et al. Sexual dysfunctions in men affected by autoimmune addison’s disease before and after short-term gluco- and mineralocorticoid replacement therapy. J Sex Med. 2013;10:2036–43. [PubMed] [Google Scholar]134. Vignozzi L, Filippi S, Morelli A, Luconi M, Jannini E, Forti G, et al. Regulation of epididymal contractility during semen emission, the first part of the ejaculatory process: a role for estrogen. J Sex Med. 2008;5:2480. [PubMed] [Google Scholar]136. Rowe P, Comhaire F. WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge University Press; Cambridge: 2000. [Google Scholar]137. Finkelstein JS, Lee H, Burnett-Bowie SAM, Pallais JC, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22. [PMC free article] [PubMed] [Google Scholar]138. Corona G, Maggi M. The role of testosterone in erectile dysfunction. Nat Rev Urol. 2010;7:46–56. [PubMed] [Google Scholar]139. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004;145:2253–63. [PubMed] [Google Scholar]140. Swaab DF. Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab. 2007;21:431–44. [PubMed] [Google Scholar]

emphasis on orgasm and ejaculation

Fertil Steril. Author manuscript; available in PMC 2016 Jun 7.

Published in final edited form as:

PMCID: PMC4896089

NIHMSID: NIHMS789951

, M.D., M.Sc.,a,b, M.D., M.A.S.,b and , M.D.b

Amjad Alwaal

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Benjamin N. Breyer

bDepartment of Urology, University of California, San Francisco, California

Tom F. Lue

bDepartment of Urology, University of California, San Francisco, California

aDepartment of Urology, King Abdulaziz University, Jeddah, Saudi Arabia

bDepartment of Urology, University of California, San Francisco, California

Reprint requests: Amjad Alwaal, M.D., M.Sc., King Abdulaziz University, Department of Urology, P. O. Box 80215, Jeddah, Saudi Arabia 21589 ([email protected]).The publisher’s final edited version of this article is available at Fertil SterilSee other articles in PMC that cite the published article.

Abstract

Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process.

Keywords: Erectile function, male sexual function, ejaculation, orgasm

Ejaculatory dysfunction is one of the most common male sexual dysfunctions that is often mis-diagnosed or disregarded. At present, there is no definitive cure for ejaculatory dysfunctions (1). New research on the physiology of ejaculation keeps emerging to identify targets of treatment. However, knowledge about this topic is still lacking. In the present article, we summarize the current literature on the physiology of ejaculation. We describe the anatomy of the organs involved and the erection physiology. We discuss the physiology of orgasm and ejaculation as two separate physiological processes. In addition, we describe the neurochemical and hormonal regulation of the ejaculation process.

FUNCTIONAL ANATOMY OF THE MALE GENITAL ORGANS

The male genital system consists of external and internal reproductive and sexual organs such as the penis, prostate, epididymis, and testes. shows the gross anatomy of the ejaculatory structures. provides a summary of the functional anatomy of these organs (2–5).

Gross anatomy of the ejaculation structures. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:15.)

TABLE 1

Summary of the functional anatomy of the male genital organs.

Organ Characteristics
Penis Composed of three chambers: paired corpora cavernosa (erectile bodies) and a midline ventral corpus spongiosum
 (contains urethra)
Main blood supply: internal pudendal artery
Somatic sensation: pudendal nerve (S2-S4)
Autonomic nerve fibers: cavernous nerves (pelvic plexus) contain both sympathetic (hypogastric plexus) and
 parasympathetic nerve fibers (S2-S4)
Urethra Four segments: prostatic urethra, membranous urethra (passes through the urogenital diaphragm), bulbar urethra,
 and penile urethra (ends with a small dilatation at the fossa navicularis near the meatus)
Cowper’s glands: located on both sides of the membranous urethra and open in the bulbar urethra
Veromontanum: small elevation of the posterior wall of the membranous urethra, related to ejaculatory ducts, prostatic
 utricle, and prostatic ducts
Testis It is divided by fibrous septa into many lobules containing seminiferous tubules
Leydig cells: main source of T production
Seminiferous tubules: contain germ cells and sertoli cells. Forms the rete testis inside the testis mediastinum
Rete testis: gives rise to 15–20 efferent ductules
Epididymis Posterior and superior to the testicle
Composed of head, body, and tail
Efferent ductules unite to form the convoluted duct of the epididymis
Becomes the vas deferens at the end of the tail
Vas deferens Muscular tube; typically 45 cm long and has a 2.5 mm diameter
It is a continuation of the epididymis
Joins the seminal vesicle duct to form the ejaculatory duct, which then drains into the veromontanum
Supplied by the vasal artery, a branch of the inferior vesical artery
Prostate Surrounds the prostatic urethra
Composed of 70% glandular component and 30% fibromuscular component
Arterial supply: inferior vesical and middle rectal arteries
Seminal
 vesicles
Paired structures; located lateral to the vas deferens
Typically 5 cm long and 1 cm wide
Joins the vas to form the ejaculatory duct
Arterial supply: inferior vesical and middle rectal arteries

PHYSIOLOGY OF ERECTION

The penile erection results from complex neurovascular mechanisms. Several central and peripheral neurological factors in addition to molecular, vascular, psychological and endocrino-logical factors are involved, and the balance between these factors is what eventually determines the functionality of the penis. In this section, we summarize some of those mechanisms.

Cerebral Control

Cerebrally controlled penile erections are induced through erotic visual stimuli or thoughts. The main cerebral structures involved in erection are contained within the medial preoptic area (MPOA) and paraventricular nucleus (PVN) in the hypothalamus (6). Dopamine is the most important brain neurotransmitter for erection, likely through its stimulation of oxytocin release (7). Another important neurotransmitter is norepinephrine, which is demonstrated through the erectogenic effect of the α-2 agonist (Yohimbine) (8). Several other brain neurotransmitters are involved in the erection process to varying degrees such as nitric oxide (NO), α-melanocyte stimulating hormone (α-MSH), and opioid peptides (9).

Autonomic Control

Parasympathetic stimulation is the main mediator for penile tumescence, although central suppression of the sympathetic nervous system also plays a role. Parasympathetic supply to the penis is derived from the sacral segments S2-S4 (10). However, patients with sacral spinal cord injury still maintain erections through psychogenic stimulation, although of less rigidity than normal. These psychogenic erections do not occur in patients with lesions above T9 (11), suggesting that the main mechanism for these erections is central suppression of sympathetic stimulation (12). Patients with lesions above T9 still may maintain reflexogenic erections. This implies that the main mechanism for reflexogenic tumescence is the preservation of the sacral reflex arc, which mediates erection through tactile penile stimulation (13, 14).

Molecular Mechanisms

The penis at baseline is in a flaccid state maintained by the contraction of corporal smooth muscles and constriction of cavernous and helicine arteries leading to moderate state of hypoxia with partial pressure of oxygen of 30–40 mm Hg (15). During sexual arousal, NO is released from cavernous nerve terminals through the action of neuronal NO synthase (16). The NO activates guanylate cyclase, which in turn converts guanosine triphosphate to cyclic guanosine monophosphate (15, 17), leading eventually to smooth muscle relaxation and vasodilation (18). Although the initiation of tumescence is through neuronal NO synthase, the maintenance of erection is through endothelial NO synthase (19). The eventual smooth muscle relaxation and vasodilation results in blood flowing into the paired corpora and filling of the sinusoids, with increased intracorporal pressure (to >100 mm Hg during full erection) and compression of the subtunical venules, markedly reducing the venous outflow (13).

PHYSIOLOGY OF ORGASM

There is no standard definition of orgasm. Each specialty such as endocrinology or psychology examines this activity from each one’s perspective, making it difficult to reach a consensus on the definition. Orgasm is generally associated with ejaculation, although the two processes are physiologically different (20). Certain physiological features are associated with orgasm, including hyperventilation up to 40 breaths/min, tachycardia, and high blood pressure (21). In fact, faster heart rate was found to be an indicator of “real” male orgasm during intravaginal intercourse, differentiating it from “fake” orgasm (22). Orgasm is also associated with powerful and highly pleasurable pelvic muscle contractions (especially ischiocavernosus and bulbocavernosus) (23), along with rectal sphincter contractions and facial grimacing (21). There is also an associated release and elevation in PRL and oxytocin levels after orgasm; however, the significance of this elevation is not entirely clear (24).

Studies using positron emission tomography, which measures changes in regional cerebral blood flow, have identified areas of activation in the brain during orgasm. Primary intense activation areas are noted to be in the mesodiencephalic transition zones, which includes the midline, the zona incerta, ventroposterior and intralaminar thalamic nuclei, the lateral segmental central field, the suprafascicular nucleus, and the ventral tegmental area. Strong increases were seen in the cerebellum. Decreases were noted at the entorhinal cortex and the amygdale (25).

Quality and intensity of orgasms are variable. For instance, short fast buildup of sexual stimulation toward orgasm is associated with less intense orgasms than slow buildup. Early orgasms are less satisfying than later orgasms in life as the person learns to accept the pleasure associated with orgasms. Lower levels of androgen are associated with weaker orgasms, such as in hypogonadism or in older age (20). It has been suggested that pelvic muscle exercises, particularly the bulbocavernosus and ischiocavernosus muscles, through contracting those muscles 60 times, 3 times daily for 6 weeks will enhance the pleasure associated with orgasm (20). However, the effort and time associated with such exercises prevent their utilization. The orgasm induced through deep prostatic massage is thought to be different from the orgasm associated direct penile stimulation. Although penile stimulation orgasms are associated with 4–8 pelvic muscle contractions, prostatic massage orgasms are associated with 12 contractions. Prostatic massage orgasms are thought to be more intense and diffuse than penile stimulation orgasms, but they require time and practice and are not liked by many men (20, 26, 27).

Following orgasm in men is a temporary period of inhibition of erection or ejaculation called the refractory period. This is a poorly understood phenomenon, with some investigators suggesting a central rather than spinal mechanism causing it (28). Elevated levels of PRL and serotonin after orgasm have been suggested as a potential cause; however, there is much debate about their exact role (29). More research is still needed in the area of male orgasm (20).

PHYSIOLOGY OF EJACULATION

Ejaculation is a physiological process heavily controlled by the autonomic nervous system. It consists of two main phases: emission and expulsion. The main organs involved in ejaculation are the distal epididymis, the vas deferens, the seminal vesicle, the prostate, the prostatic urethra, and the bladder neck (30).

Emission

The first step in the emission phase is the closure of bladder neck to prevent retrograde spillage of the seminal fluid into the bladder. This is followed by the ejection of prostatic secretions (10% of the final semen volume) containing acid phosphatase, citric acid, and zinc, mixed with spermatozoa from the vas deferens (10% of the volume) into the prostatic urethra. Subsequently, the fructose-containing seminal vesicle fluid alkalinizes the final ejaculatory fluid. The seminal vesicle fluid constitutes 75%–80% of the final seminal fluid. Cowper’s glands and periurethral glands produce a minority of the seminal fluid (1, 31). The organs involved in the ejaculation process receive dense autonomic nerve supply, both sympathetic and parasympathetic, from the pelvic plexus. The pelvic plexus is located retroperitoneally on either side of the rectum, lateral and posterior to the seminal vesicle (32). It receives neuronal input from the hypogastric and pelvic nerves in addition to the caudal paravertebral sympathetic chain (33). The sympathetic neurons play the predominant role in the ejaculation process. Their nerve terminals secrete primarily norepinephrine, although other neurotransmitters such as acetylcholine and nonadrenergic/noncholinergic also play important roles (34). The role of the hypogastric plexus in emission is best demonstrated clinically by the loss of emission after non-nerve sparing para-aortic lymph node dissection for testicular cancer (35), and induction of emission in paraplegic men through electrical stimulation of superior hypogastric plexus (35). Input from genital stimulation is integrated at the neural sacral spinal level to produce emission (36). The emission phase of ejaculation is also under a considerable cerebral control, and can be induced through physical or visual erotic stimulation (37).

Expulsion

Expulsion follows emission as the process of ejaculation climaxes, and refers to the ejection of semen through the urethral meatus. The semen is propelled through the rhythmic contractions of the pelvic striated muscles in addition to the bulbospongiosus and ischiocavernosus muscles (23). To achieve antegrade semen expulsion, the bladder neck remains closed, whereas the external urethral sphincter is open. The external sphincter and the pelvic musculature are under somatic control; however, there is no evidence that voluntary control plays a role in the expulsion process (30). The exact trigger for expulsion is unknown. It has been suggested that a spinal center is triggered during emission of seminal fluid into the prostatic urethra (38). However, there is mounting evidence through clinical and experimental studies to suggest that this is not the case. For instance, men can still have rhythmic contractions during orgasm despite “dry ejaculation,” for example, due to prostatectomy (23, 39, 40). This, in addition to the identification of spinal generator for ejaculation (SGE) in rats, led to the postulation that the process of expulsion is a continuum of the process initiated through emission, after reaching a certain spinal activation threshold (30, 41).

NEURONAL CONTROL OF EJACULATION

Ejaculation is heavily controlled by the nervous system. summarizes the reflex circuit necessary to elicit ejaculation.

Reflex circuit needed to establish ejaculation. (Reprinted with permission from Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, eds. Men’s sexual health and fertility: a clinician’s guide. New York: Springer; 2014:18.)

Peripheral Nervous System

Afferents

The main sensory input from the penis comes from the dorsal nerve of the penis, which transmits sensation from the glans, prepuce, and penile shaft. It transmits signals to the upper and lower segments of the sacral spinal cord (42). The glans contains encapsulated nerve endings, termed Krause-Finger corpuscles, whereas the remaining penile shaft contains free nerve endings. Stimulation of these corpuscles potentiated by stimulation from other genital areas, such the perineum, testes, and penile shaft, play an important role in the ejaculation process (43). A secondary afferent route is through the hypogastric nerve, which runs through the paravertebral sympathetic chain to enter the spinal cord through the thoracolumbar dorsal roots (44). The sensory afferents terminate in the medial dorsal horn and the dorsal gray commissure of the spinal cord (45).

Efferents

The efferent peripheral nervous system constitutes of sympathetic, parasympathetic, and motor nervous components (46). The soma of the preganglionic sympathetic cell bodies involved in ejaculation are located in the intermedio-lateral cell column and in the central autonomic region of the thoracolumbar segments (T12-L1) (47). The preganglionic sympathetic fibers emerge from the ventral roots of the spinal cord and travel through the paravertebral sympathetic chain to relay either directly through the splanchnic nerve, or through relaying first in the celiac superior mesenteric ganglia and then through the intermesenteric nerve, to the inferior mesenteric ganglia (48). The hypogastric nerve then emanates from the inferior mesenteric ganglia to join the parasympathetic pelvic nerve to form the pelvic plexus, which then sends fibers to the ejaculation structures (49). The preganglionic parasympathetic cell bodies are located in the sacral parasympathetic nucleus. The sacral parasympathetic nucleus neurons travel then in the pelvic nerve to the post-ganglionic parasympathetic cells located in the pelvic plexus. The motor neurons involved in ejaculation are located in Onuf’s nucleus in the sacral spinal cord, which projects fibers through the motor component of the pudendal nerve to reach the pelvic musculature, including the bulbospongiosus, ischiocavernosus, and external urethral sphincter (50).

Central Nervous System

Spinal network

The thoracolumbar sympathetic, sacral parasympathetic (mainly sacral parasympathetic nucleus), and somatic sacral Onuf’s nucleus ejaculatory spinal nuclei play an important role in the integration of peripheral and cerebral input and coordinating output to the pelviperineal structures involved in ejaculation (46). An additional spinal center is the SGE located in laminae X and VII of L3-L4 spinal segments (51). The SGE contains spinal interneurons called lumbar spinothalamic cells, which project fibers to the parvocellular subparafascicular nucleus of the thalamus in addition to preganglionic sympathetic and parasympathetic neurons innervating the pelvis (41). The SGE stimulation elicits a complete ejaculatory response resulting in collection of motile spermatozoa in anesthetized rats (52). Further research on the SGE spinal center is still needed, and it is unclear whether it contains other cells than lumbar spinothalamic cells.

Brain network

Sensory and motor areas in the brain play an important role in the ejaculation, which requires a highly coordinated and integrated central process. The study by Holstege et al. (25) using positron emission tomography showed that certain areas in the brain are activated in the orgasm and ejaculation process. Furthermore, specific areas in the brain have been involved in the ejaculation process, as demonstrated in animal immunohistochemical studies examining Fos protein pattern of expression (53–56), and confirmed using a serotonin 1A subtype receptor agonist proejaculatory pharmacologic agent in rats (57). These are discrete areas within the posteromedial bed nucleus of stria terminalis, the parvicellular part of the subparafascicular thalamus, the posterodorsal preoptic nucleus, and the posterodorsal medial amygdaloid nucleus. There are reciprocal connections that link those areas to the MPOA of the hypothalamus, a brain area with a well-established role in controlling sexual behavior as demonstrated by anatomical and functional studies (54, 55, 58). Electrical or chemical stimulation of the MPOA elicited ejaculation (59–62), whereas an MPOA lesion was shown to abolish both phases of ejaculation (63). No direct connections of MPOA to the spinal centers for ejaculation were found on neuroanatomical studies; however, there are projections of MPOA to other regions in the brain involved in ejaculation, such as PVN, the periaqueductal gray, and the paragigantocellular nucleus (nPGi) (64–66).

The PVN projects to pudendal motor neurons located in the L5-L6 spinal segment in addition to autonomic preganglionic neurons in the lumbosacral spinal cord in rats (45, 67, 68). It also projects to nPGI in the brainstem (69). Bilateral lesions of the PVN with N-methyl-D-aspartate (NMDA) results in a one-third reduction of the seminal ejaculate material weight (70). The parvicellular part of the subparafascicular thalamus was found to send projections to bed nucleus of stria terminalis, medial amygdala (MeA), and MPOA (71, 72) and receives input from lumbar spinothalamic cells (51). The precise role of these regions is still unclear but they are likely involved in relaying genital signals to MPOA (53, 55). The brainstem regions (nPGI and periaqueductal gray) have recently received increasing attention. The nPGI nucleus likely plays an inhibitory role in ejaculation as evidenced through the urethrogenital reflex experimental model, a rat model for the expulsion phase of ejaculation (73, 74). Using the same model, the periaqueductal gray was found to be important for the ejaculation process, likely by acting as a relay between MPOA and nPGI (75). Midbrain structures have a significant role in ejaculation; however, much is still unknown about their exact role and further research is needed. summarizes the putative brain structures involved in ejaculation.

Putative brain structures involved in ejaculation. BNSTpm = posteromedial bed nucleus of stria terminalis; MeApd = posterodorsal medial amygdaloid nucleus; MPOA = medial preoptic area; PAG = periaqueductal gray; nPGi = paragigantocellular nucleus; PNpd = posterodorsal preoptic nucleus; PVN = paraventricular thalamic nucleus; SPFp = parvicellular part of the subparafascicular thalamus. (Reprinted with permission from Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, Rosen RC, eds. Cancer and sexual health. New York: Springer; 2011:82.)

NEUROCHEMICAL REGULATION OF EJACULATION

Many neurotransmitters are involved in the ejaculation process. Defining the exact role of these neurotransmitters is difficult given the variety of sexual parameters affected, the different sites of action within the spinal and the supraspinal pathways, and the presence of multiple receptor types. Some of the molecules that received special attention for their role in ejaculation are mentioned later.

Dopaminergic Control

Dopamine is known to be important for normal male sexual response (76, 77). Two families of dopamine receptors exist, D1-like (D1 and D5 receptors) and D2-like (D2, D3, and D4 receptors) (46). In rats, D2-like receptors are known to stimulate ejaculation (78, 79), and trigger ejaculation even in anesthetized rats (80, 81). Systemic injection of the D3 receptor agonist 7-OH-DPAT has been shown to trigger ejaculation in rats without affecting arousal (82, 83). It also triggers ejaculation in anesthetized rats when injected directly into the cerebral ventricles or MPOA with the effect being specifically reversed by the D3, not the D2 antagonist (84, 85). The D3 receptor blockage has been shown to inhibit the expulsion phase of ejaculation and lengthen ejaculation latency in rats (86).

Serotonergic Control

Evidence suggests that serotonin (5HT) inhibits ejaculation (87). Selective serotonin reuptake inhibitors increase 5HT tone resulting in impairment of ejaculation, which led to their clinical use in premature ejaculation. This inhibitory effect is likely to occur in the brain (88), as 5HT effect on ejaculation in the spine is likely stimulatory (89). The amphetamine derivative p-chloroamphetamine leads to a sudden release of 5HT in synaptic clefts triggering ejaculation in anesthetized rats with complete spinal cord lesion (89). Intrathecal serotonin or selective serotonin reuptake inhibitor injection leads to enhancement of the expulsion phase of ejaculation (88). There are 14 receptor subtypes for 5HT, with 1A, 1B, and 2C being the ones involved in ejaculation (90). It is difficult to designate one influence for each receptor subtype, as each receptor could either activate or inhibit ejaculation depending on its location within the central nervous system (46).

Nitric Oxide

The role of NO in ejaculation has received special attention after the introduction of type-5 phosphodiesterase (PDE5) inhibitors and using them for premature ejaculation. Nitric oxide has an inhibitory role on the ejaculation process (1). Centrally, intrathecal sildenafil results in elevation of NO and cyclic guanosine monophosphate levels in MPOA causing a decreased peripheral sympathetic tone and inhibition of ejaculation (91). N-Nitro-l-arginine methyl-ester injection, an NO synthase inhibitor, was shown to increase the number of seminal emissions and reduce latency to first seminal emission in rats (92). Peripherally, nitronergic innervation and NO synthase were found in the seminal vesicle, vas deferens, prostate, and urethra (93–97). Therefore, drugs such as PDE5 inhibitors or NO donors are associated with reduced seminal vesicle contraction and inhibit seminal emission (92). The administration of NO inhibitors, such as l-nitroarginine-methylester, diminishes human seminal vesicle contraction (98), inhibits vasal contraction in guinea pigs (99), and decreases latency to ejaculation in rats (100). Furthermore, reduced latency to emission was found in knockout mice for the gene encoding endothelial NO synthase compared with their wild-type counterparts (101).

HORMONAL REGULATION OF EJACULATION

Although male sexual function is heavily regulated by the hormonal system, there are few clinical studies performed to evaluate hormonal regulation of ejaculation, and the knowledge about hormonal effect on ejaculation is still lacking. We discuss some of the studies examining the effect of different hormones on ejaculation.

Oxytocin

Oxytocin is an oligopeptide synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland. Oxytocin serum level increases after male ejaculation to levels ranging from 20%–360% of normal levels before reaching baseline at 10 minutes after ejaculation (102). Pharmacologic oxytocin administration in humans and animals results in increased ejaculated spermatozoa (103), confirming that oxytocin has a role in male genital tract motility. It was specifically found to augment powerful epididymal contractions and sperm motility (104), an important effect blunted by pretreatment with the oxytocin antagonist (des Gly–Nh3d(Ch3)5–[d-Tyr2,Thr4] ornithine vasotocin) (105). Peripheral oxytocin receptors were found to be highly expressed in the epididymis and tunica albuginea (in smooth muscles more than epithelial cells), and to a lesser extent in the vas deferens and seminal vesicle (104). Oxytocin has a synergistic action on the epididymis with endothelin-1, where they augment epididymal contraction and propel spermatozoa forward (102, 106). Injection of oxytocin into the cerebral ventricles in male rats facilitated ejaculation by shortening the ejaculation latency and postejaculatory refractory periods (107), whereas these effects were curbed using the oxytocin receptor antagonist (d(Ch3)5–Tyr(Me)–[Orn8]vasotocin) injected into the cerebral ventricles (108). Despite these encouraging findings and some anecdotal evidence suggesting that intranasal oxytocin can facilitate orgasm in an anorgasmic male (109), a double-blind placebo-controlled clinical study (110) failed to demonstrate an effect of intranasal oxytocin on sexual behavior.

Prolactin

Hyperprolactinemia has a marked inhibitory effect on male sexual desire (111). A modest increase in serum PRL levels (15–20 ng/mL) has been detected in men after orgasm, and could be contributing to the after-orgasm refractory period (112). Some investigators have hypothesized that a low PRL level is a cause of premature ejaculation, where PRL levels were similarly low in those men with lifelong or acquired premature ejaculation (113). Further research is needed on this issue.

Thyroid Hormones

The relationship between thyroid hormonal abnormalities and ejaculatory dysfunction has been well documented (114–116). In rats, l-thyroxin administration has been shown to increase bulbospongiosus contractile activity and seminal vesicle contraction frequency (117). Clinically, the prevalence of suppressed TSH, which is a marker of hyperthyroidism, was found to be twofold higher in patients with premature ejaculation than in patients who reported normal ejaculatory timing (118). In the first prospective multicenter study (114) on the topic, half of hyperthyroidism patients had premature ejaculation, whereas only 15% reported this symptom after cure of their thyroid dysfunction. Another single-center prospective study by Cihan et al. (116) demonstrated a prevalence of 72% of premature ejaculation in hyperthyroidism, which was reduced after treatment. It also identified a positive correlation of TSH with intravaginal ejaculation latency time. Öztürk et al. (119) found similar results. However, Waldinger et al. (120) found no correlation between TSH and intravaginal ejaculation latency time in a cohort of Dutch men with lifelong premature ejaculation. A meta-analysis by Corona et al. (102) demonstrated a threefold increase of hyperthyroidism in patients with premature ejaculation compared with controls, a finding that was more pronounced in patients with acquired rather than lifelong premature ejaculation. They also showed an increase in intravaginal ejaculation latency time by 84.6 ± 34.2 seconds (P=.001) upon treatment of hyperthyroidism. These findings suggest that thyroid hormones do not only affect the ankle reflex, but also the ejaculatory reflex, and screening patients with ejaculatory dysfunction for thyroid hormone abnormalities is warranted (102).

Glucocorticoids

Cortisol (F) levels in several animal studies were found to be elevated during arousal and ejaculation (121–123). In horses and donkeys, F was elevated 30 minutes after ejaculation, with unknown significance of this finding (124, 125). In addition, F levels were sharply elevated after electroejaculation in several anesthetized animal studies (126, 127). In humans, however, there was no change in F levels whether during sexual stimulation or orgasm (128–131). Although hypercortisolism in men was associated with reduced libido, no effect was identified on orgasm or ejaculation (132). Replacement of F in Addison disease was associated with improvement in overall sexual function including orgasm (133). Data in humans are still too preliminary to draw final conclusions, and further research is needed.

Estrogens

Estradiol plays an important role in the regulation of the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid reabsorption, and sperm concentration (134, 135). This role in the epididymis is the reason for recommending Tamoxifen as a first-line treatment for idiopathic oligospermia by the World Health Organization (136). Finkelstein et al. (137) showed that E2 deficiency, along with androgen deficiency, contributes to decreased libido and erectile function.

Androgens

Testosterone, through its central and peripheral androgen receptors, has a well-known role on male sexual function, particularly on libido (138). Low T levels are associated with delayed ejaculation, whereas high levels were associated with premature ejaculation (102). This is likely because the emission phase of the ejaculation relies on the NO-PDE5 system, which is influenced by T (138, 139). Testosterone facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other areas in the central nervous system (140). Furthermore, pelvic floor muscles involved in ejaculation are androgen dependent (141). There are likely multiple mechanisms involved in T action and further research is needed to identify specific targets for treatment in the ejaculatory reflex. summarizes the neurochemical and hormonal regulation of ejaculation.

TABLE 2

Neurochemical and hormonal regulation of ejaculation.

Neurotransmitter/hormone Effect
Dopamine Stimulates ejaculation through D2-like receptors (D2, D3, and D4 receptors, mainly D3)
Serotonin Inhibits ejaculation in the brain and stimulates it in the spine through the receptors 5HT, with 1A, 1B, and 2C
Nitric oxide Inhibits ejaculation through reduction of seminal vesicle contraction and seminal emission
Oxytocin Synthesized in the supraoptic and PVN of the hypothalamus and released from the posterior pituitary gland
Augments powerful epididymal contractions and sperm motility
Acts in the CNS to stimulate ejaculation
Prolactin Secreted from the pituitary gland
Hyperprolactinemia has a marked inhibitory effect on male sexual desire, through inhibition of GnRH
 (therefore T production) and dopamine production
Thyroid hormones Hypothyroidism and hyperthyroidism are associated with delayed and premature ejaculation, respectively
Glucocorticoids Cortisol levels are elevated after ejaculation in animal studies
No change in cortisol levels in humans
Replacement of cortisol in Addison disease improves sexual function including orgasm
Estrogens Regulates the emission phase of ejaculation through the regulation of epididymal contractility, luminal fluid
 reabsorption, and sperm concentration
Androgens Low levels are associated with delayed ejaculation, whereas high levels are associated with premature ejaculation
Facilitates the control of the ejaculatory reflex through its androgen receptors in the MPOA and other
 areas in the CNS
Pelvic floor muscles involved in ejaculation are androgen dependent

In conclusion, ejaculation is a complex process involving several anatomical structures and under extensive neurochemical and hormonal regulation. Orgasm, although associated with ejaculation, is a distinct physiological process, different from ejaculation. Many aspects of these physiological processes are still unknown and further research is needed to identify treatments for ejaculatory dysfunction.

Footnotes

A.A. has nothing to disclose. B.N.B. has nothing to disclose. T.F.L. has nothing to disclose.

REFERENCES

1. Sheu G, Revenig LM, Hsiao W. Physiology of ejaculation. In: Mulhall JP, Hsiao W, editors. Men’s sexual health and fertility. Springer Science; New York: 2014. pp. 13–29. [Google Scholar]2. Bella AJ, Shamloul R. Functional anatomy of the male sex organs. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 3–12. [Google Scholar]3. Meacham R, Lipshultz L, Howards S. Male infertility. In: Gillenwater JY, Grayhack JT, Howards S, Duckett JW, editors. Adult and pediatric urology. Mosby; St. Louis: 1996. pp. 1747–802. [Google Scholar]4. Hinman F. Normal surgical anatomy. In: Thomas Thomas AJ, Nagler HN, editors. Atlas of surgical management of male infertility. William & Wilkins; New York: 1995. pp. 9–20. [Google Scholar]5. Romanes G. The pelvis and perineum. In: Romanes G, Cunningham D, editors. Cunningham’s manual of practical anatomy. 13th ed Oxford University Press; London, UK: 1975. pp. 199–240. [Google Scholar]6. Tang Y, Rampin O, Calas A, Facchinetti P, Giuliano F. Oxytocinergic and serotonergic innervation of identified lumbosacral nuclei controlling penile erection in the male rat. Neuroscience. 1998;82:241–54. [PubMed] [Google Scholar]7. Danjou P, Lacomblez L, Warot D, Puech AJ. Assessment of erectogenic drugs by numeric plethysmography. J Pharmacol Methods. 1989;21:61–9. [PubMed] [Google Scholar]8. Clark JT, Smith ER, Davidson JM. Testosterone is not required for the enhancement of sexual motivation by yohimbine. Physiol Behav. 1985;35:517–21. [PubMed] [Google Scholar]9. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63:811–59. [PubMed] [Google Scholar]10. Lue TF, Zeineh SJ, Schmidt RA, Tanagho EA. Neuroanatomy of penile erection: its relevance to iatrogenic impotence. J Urol. 1984;131:273–80. [PubMed] [Google Scholar]11. Paick JS, Lee SW. The neural mechanism of apomorphine-induced erection: an experimental study by comparison with electrostimulation-induced erection in the rat model. J Urol. 1994;152(6 Pt 1):2125–8. [PubMed] [Google Scholar]12. Chapelle PA, Durand J, Lacert P. Penile erection following complete spinal cord injury in man. Br J Urol. 1980;52:216–9. [PubMed] [Google Scholar]14. Courtois FJ, Charvier KF, Leriche A, Raymond DP. Sexual function in spinal cord injury men. I. Assessing sexual capability. Paraplegia. 1993;31:771–84. [PubMed] [Google Scholar]15. Sattar AA, Salpigidis G, Schulman CC, Wespes E. Relationship between intrapenile O2 lever and quantity of intracavernous smooth muscle fibers: current physiopathological concept. Acta Urol Belg. 1995;63:53–9. [PubMed] [Google Scholar]16. Prieto D. Physiological regulation of penile arteries and veins. Int J Impot Res. 2007;20:17–29. [PubMed] [Google Scholar]17. Andersson KE. Pharmacology of penile erection. Pharmacol Rev. 2001;53:417–50. [PubMed] [Google Scholar]18. Walsh MP. The Ayerst Award Lecture 1990. Calcium-dependent mechanisms of regulation of smooth muscle contraction. Biochem Cell Biol. 1991;69:771–800. [PubMed] [Google Scholar]19. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci. 2002;99:4061–6. [PMC free article] [PubMed] [Google Scholar]20. Levin R. Physiology of orgasm. In: Mulhall JP, Incocci L, Goldstein I, Rosen R, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 35–48. [Google Scholar]21. Masters W, Johnson V. Human sexual response. Little Brown; Boston: 1966. [Google Scholar]22. Levin R, editor. Heart rate responses can be used to differentiate simulated from real orgasms in the human male: a pilot study. Proceedings of the first conference on orgasm. VRP Publishers; Bombay: 1991. [Google Scholar]23. Gerstenberg TC, Levin RJ, Wagner G. Erection and ejaculation in man—assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles. Br J Urol. 1990;65:395–402. [PubMed] [Google Scholar]24. Levin R. Is prolactin the biological ‘off switch’ for human sexual arousal? Sex Relat Ther. 2003;18:289–343. [Google Scholar]25. Holstege G, Georgiadis JR, Paans AM, Meiners LC, van der Graaf FH, Reinders AS. Brain activation during human ejaculation. J Neurosci. 2003;23:9185–93. [PMC free article] [PubMed] [Google Scholar]26. Hite S. The Hite report on male sexuality. Ballantine Books; New York: 1981. [Google Scholar]27. Perry JF. Do men have a G-spot? Aust Forum. 1988;2:37–41. [Google Scholar]28. Levin R. Revisiting post-ejaculatory refractory time—what we know and what we do not know in males and females. J Sex Med. 2009;6:2376–89. [PubMed] [Google Scholar]29. Turley KR, Rowland DL. Evolving ideas about the male refractory period. BJU Int. 2013;112:442–52. [PubMed] [Google Scholar]30. Giuliano F, Clement P. Physiology of ejaculation: emphasis on serotonergic control. Eur Urol. 2005;48:408–17. [PubMed] [Google Scholar]31. Master VA, Turek PJ. Ejaculatory physiology and dysfunction. Urol Clin North Am. 2001;28:363–75. [PubMed] [Google Scholar]32. Schlegel PN, Walsh PC. Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol. 1987;16:46–60. [PubMed] [Google Scholar]33. Keast JR. Pelvic ganglia. In: McLahlan EM, editor. Autonomic ganglia. Harwood Academic; Luxemberg: 1995. pp. 445–79. [Google Scholar]34. Dail WG, Moll MA. Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat. Neuroscience. 1983;10:1379–86. [PubMed] [Google Scholar]35. Brindley GS, Sauerwein D, Hendry WF. Hypogastric plexus stimulators for obtaining semen from paraplegic men. Br J Urol. 1989;64:72–7. [PubMed] [Google Scholar]36. Ver Voort SM. Ejaculatory stimulation in spinal-cord injured men. Urology. 1987;29:282–9. [PubMed] [Google Scholar]37. Comarr A. Sexual function among patients with spinal cord injury. Urol Int. 1970;25:134–68. [PubMed] [Google Scholar]38. McKenna KE, Chung SK, McVary KT. A model for the study of sexual function in anesthetized male and female rats. Am J Physiol. 1991;261:R1276–85. [PubMed] [Google Scholar]39. Bergman B, Nilsson S, Petersen I. The effect on erection and orgasm of cystectomy, prostatectomy and vesiculectomy for cancer of the bladder: a clinical and electromyographic study. Br J Urol. 1979;51:114–20. [PubMed] [Google Scholar]40. Holmes GM, Sachs BD. The ejaculatory reflex in copulating rats: normal bulbospongiosus activity without apparent urethral stimulation. Neurosci Lett. 1991;125:195–7. [PubMed] [Google Scholar]41. Truitt WA, Coolen LM. Identification of a potential ejaculation generator in the spinal cord. Science. 2002;297:1566–9. [PubMed] [Google Scholar]42. Nunez R, Gross GH, Sachs BD. Origin and central projections of rat dorsal penile nerve: possible direct projection to autonomic and somatic neurons by primary afferents of nonmuscle origin. J Comp Neurol. 1986;247:417–29. [PubMed] [Google Scholar]43. Halata Z, Munger BL. The neuroanatomical basis for the protopathic sensibility of the human glans penis. Brain Res. 1986;371:205–30. [PubMed] [Google Scholar]44. Baron R, Janig W. Afferent and sympathetic neurons projecting into lumbar visceral nerves of the male rat. J Comp Neurol. 1991;314:429–36. [PubMed] [Google Scholar]45. McKenna KE, Nadelhaft I. The organization of the pudendal nerve in the male and female rat. J Comp Neurol. 1986;248:532–49. [PubMed] [Google Scholar]46. Clement P, Giuliano F. Physiology of ejaculation. In: Mulhall JP, Incrocci L, Goldstein I, editors. Cancer and sexual health. Springer Science; New York: 2011. pp. 77–89. [Google Scholar]47. Morgan C, de Groat WC, Nadelhaft I. The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat. J Comp Neurol. 1986;243:23–40. [PubMed] [Google Scholar]48. Owman C, Stjernquist M. The peripheral nervous system. In: Bjorklund A, Hokfelt T, Owman C, editors. Handbook of chemical neuroanatomy. Elsevier Science; Amsterdam, The Netherlands: 1988. pp. 445–544. [Google Scholar]49. Nadelhaft I, Booth AM. The location and morphology of preganglionic neurons and the distribution of visceral afferents from the rat pelvic nerve: a horseradish peroxidase study. J Comp Neurol. 1984;226:238–45. [PubMed] [Google Scholar]50. Schroder HD. Anatomical and pathoanatomical studies on the spinal efferent systems innervating pelvic structures. 1. Organization of spinal nuclei in animals. 2. The nucleus X-pelvic motor system in man. J Auton Nerv Syst. 1985;14:23–48. [PubMed] [Google Scholar]51. Coolen LM, Veening JG, Wells AB, Shipley MT. Afferent connections of the parvocellular subparafascicular thalamic nucleus in the rat: evidence for functional subdivisions. J Comp Neurol. 2003;463:132–56. [PubMed] [Google Scholar]52. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Ejaculation elicited by microstimulation of lumbar spinothalamic neurons. Eur Urol. 2008;54:449–56. [PubMed] [Google Scholar]53. Hamson DK, Watson NV. Regional brainstem expression of Fos associated with sexual behavior in male rats. Brain Res. 2004;1006:233–40. [PubMed] [Google Scholar]54. Heeb MM, Yahr P. Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation. J Comp Neurol. 2001;439:248–58. [PubMed] [Google Scholar]55. Coolen LM, Peters HJ, Veening JG. Anatomical interrelationships of the medial preoptic area and other brain regions activated following male sexual behavior: a combined fos and tract-tracing study. J Comp Neurol. 1998;397:421–35. [PubMed] [Google Scholar]56. Kollack-Walker S, Newman SW. Mating-induced expression of c-fos in the male Syrian hamster brain: role of experience, pheromones, and ejaculations. J Neurobiol. 1997;32:481–501. [PubMed] [Google Scholar]57. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F. Demonstration of ejaculation-induced neural activity in the male rat brain using 5-HT1A agonist 8-OH-DPAT. Physiol Behav. 1997;62:881–91. [PubMed] [Google Scholar]58. Meisel R, Sachs B. The physiology of male sexual behavior. In: Knobil E, Neill J, editors. The physiology of reproduction. Raven; New York: 1994. pp. 3–105. [Google Scholar]59. Pehek EA, Thompson JT, Hull EM. The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res. 1989;500:325–32. [PubMed] [Google Scholar]60. Hull EM, Eaton RC, Markowski VP, Moses J, Lumley LA, Loucks JA. Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation. Life Sci. 1992;51:1705–13. [PubMed] [Google Scholar]61. Marson L, McKenna KE. Stimulation of the hypothalamus initiates the urethrogenital reflex in male rats. Brain Res. 1994;638:103–8. [PubMed] [Google Scholar]62. Larsson K, van Dis H. Seminal discharge following intracranial electrical stimulation. Brain Res. 1970;23:381–6. [PubMed] [Google Scholar]63. Arendash GW, Gorski RA. Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats. Brain Res Bull. 1983;10:147–54. [PubMed] [Google Scholar]64. Simerly RB, Swanson LW. Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol. 1988;270:209–42. [PubMed] [Google Scholar]65. Rizvi TA, Ennis M, Shipley MT. Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: A WGA-HRP and PHA-L study. J Comp Neurol. 1992;315:1–15. [PubMed] [Google Scholar]66. Murphy AZ, Rizvi TA, Ennis M, Shipley MT. The organization of preoptic medullary circuits in the male rat: evidence for interconnectivity of neural structures involved in reproductive behavior, antinociception and cardiovascular regulation. Neuroscience. 1999;91:1103–16. [PubMed] [Google Scholar]67. Saper CB, Loewy AD, Swanson LW, Cowan WM. Direct hypothalamo-autonomic connections. Brain Res. 1976;117:305–12. [PubMed] [Google Scholar]68. Luiten PG, Ter Horst GJ, Karst H, Steffens AB. The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res. 1985;329:374–8. [PubMed] [Google Scholar]69. Bancila M, Verge D, Rampin O, Backstrom JR, Sanders-Bush E, McKenna KE, et al. 5-Hydroxytryptamine2C receptors on spinal neurons controlling penile erection in the rat. Neuroscience. 1999;92:1523–37. [PubMed] [Google Scholar]70. Ackerman AE, Lange GM, Clemens LG. Effects of paraventricular lesions on sex behavior and seminal emission in male rats. Physiol Behav. 1997;63:49–53. [PubMed] [Google Scholar]71. Yasui Y, Saper CB, Cechetto DF. Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat. J Comp Neurol. 1991;308:293–310. [PubMed] [Google Scholar]72. Canteras NS, Simerly RB, Swanson LW. Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat. J Comp Neurol. 1995;360:213–45. [PubMed] [Google Scholar]73. Marson L, McKenna KE. A role for 5-hydroxytryptamine in descending inhibition of spinal sexual reflexes. Exp Brain Res. 1990;88:313–20. [PubMed] [Google Scholar]74. Marson L, McKenna KE. The identification of a brainstem site controlling spinal sexual reflexes in male rats. Brain Res. 1990;515:303–8. [PubMed] [Google Scholar]75. Marson L. Lesions of the periaqueductal gray block the medial preoptic area-induced activation of the urethrogenital reflex in male rats. Neurosci Lett. 2004;367:278–82. [PubMed] [Google Scholar]76. Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: influences on male sexual behavior. Physiol Behav. 2004;83:291–307. [PubMed] [Google Scholar]77. Peeters M, Giuliano F. Central neurophysiology and dopaminergic control of ejaculation. Neurosci Biobehav Rev. 2007;32:438–53. [PubMed] [Google Scholar]78. Ferrari F, Giuliani D. The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat. Life Sci. 1994;55:1155–62. [PubMed] [Google Scholar]79. Ferrari F, Giuliani D. Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919. Pharmacol Biochem Behav. 1995;50:29–34. [PubMed] [Google Scholar]80. Clément P, Bernabé J, Kia HK, Alexandre L, Giuliano F. D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino) tetralin in rats. J Pharmacol Exp Ther. 2006;316:830–4. [PubMed] [Google Scholar]81. Stafford SA, Coote JH. Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats. Br J Pharmacol. 2006;148:510–6. [PMC free article] [PubMed] [Google Scholar]82. Ferrari F, Giuliani D. Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats. Neuropharmacology. 1996;35:279–84. [PubMed] [Google Scholar]83. Ahlenius S, Larsson K. Effects of the dopamine D3 receptor ligand 7-OH-DPAT on male rat ejaculatory behavior. Pharmacol Biochem Behav. 1995;51:545–7. [PubMed] [Google Scholar]84. Clement P, Bernabe J, Denys P, Alexandre L, Giuliano F. Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats. Neuroscience. 2007;145:605–10. [PubMed] [Google Scholar]85. Kitrey ND, Clément P, Bernabé J, Alexandre L, Giuliano F. Microinjection of the preferential dopamine receptor D3 agonist 7-OH-DPAT into the hypothalamic medial preoptic area induced ejaculation in anesthetized rats. Neuroscience. 2007;149:636–41. [PubMed] [Google Scholar]86. Clément P, Pozzato C, Heidbreder C, Alexandre L, Giuliano F, Melotto S. Delay of ejaculation induced by SB-277011, a selective dopamine D3 receptor antagonist, in the rat. J Sex Med. 2009;6:98–108. [PubMed] [Google Scholar]87. Giuliano F. 5-hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention. Trends Neurosci. 2007;30:79–84. [PubMed] [Google Scholar]88. Clément P, Bernabé J, Gengo P, Denys P, Laurin M, Alexandre L, et al. Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine. Eur Urol. 2007;51:825–32. [PubMed] [Google Scholar]89. Stafford SA, Bowery NG, Tang K, Coote JH. Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats. Neuroscience. 2006;140:1031–40. [PubMed] [Google Scholar]90. Giuliano F, Clement P. Serotonin and premature ejaculation: from physiology to patient management. Eur Urol. 2006;50:454–66. [PubMed] [Google Scholar]91. Sato Y, Zhao W, Christ GJ. Central modulation of the NO/cGMP pathway affects the MPOAinduced intracavernous pressure response. Am J Physiol Regul Integr Com Physiol. 2001;281:R269–78. [PubMed] [Google Scholar]92. Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS. The roles of nitric oxide in sexual function of male rats. Neuropharmacology. 1994;33:1499–504. [PubMed] [Google Scholar]93. Dixon JS, Jen PY. Development of nerves containing nitric oxide synthase in the human male urogenital organs. Br J Urol. 1995;76:719–25. [PubMed] [Google Scholar]94. Hedlund P, Ekström P, Larsson B, Alm P, Andersson KE. Heme oxygen-ase and NO-synthase in the human prostate—relation to adrenergic, cholinergic and peptide-containing nerves. J Auton Nerv Syst. 1997;63:115–26. [PubMed] [Google Scholar]95. Jen PY, Dixon JS, Gosling JA. Co-localization of nitric oxide synthase, neuropeptides and tyrosine hydroxylase in nerves supplying the human postnatal vas deferens and seminal vesicle. Br J Urol. 1997;80:291–9. [PubMed] [Google Scholar]96. Kaminski HJ, Andrade FH. Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord. 2001;11:517–24. [PubMed] [Google Scholar]97. Ückert S, Bazrafshan S, Scheller F, Mayer ME, Jonas U, Stief CG. Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors. Urology. 2007;70:185–9. [PubMed] [Google Scholar]98. Bultmann R, Klebroff W, Starke K. Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms. Eur J Pharmacol. 2002;436:135–43. [PubMed] [Google Scholar]99. Kato K, Furuya K, Tsutsui I, Ozaki T, Yamagishi S. Cyclic AMP-mediated inhibition of noradrenaline-induced contraction and Ca2+ in flux in guinea-pig vas deferens. Exp Physiol. 2000;85:387–98. [PubMed] [Google Scholar]100. Bialy M, Beck J, Abramczyk P, Trzebskj A, Przybylski J. Sexual behavior in male rats after nitric oxide synthesis inhibition. Physiol Behav. 1996;60:139–43. [PubMed] [Google Scholar]101. Kriegsfeld LJ, Demas GE, Huang PL, Burnett AL, Nelson RJ. Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS) Physiol Behav. 1999;67:561–6. [PubMed] [Google Scholar]102. Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9:508–19. [PubMed] [Google Scholar]103. Maggi M, Kassis S, Malozowski S. Identification and characterization of a vasopressin isoreceptor in porcine seminal vesicles. Proc Natl Acad Sci. 1986;83:8824–8. [PMC free article] [PubMed] [Google Scholar]104. Filippi S, Vannelli GB, Granchi S. Identification, localization and functional activity of oxytocin receptors in epididymis. Mol Cell Endocrinol. 2002;193:89–100. [PubMed] [Google Scholar]105. Nicholson HD, Parkinson TJ, Lapwood KR. Effects of oxytocin and vasopressin on sperm transport from the cauda epididymis in sheep. J Reprod Fertil. 1999;117:299–305. [PubMed] [Google Scholar]106. Einspanier A, Ivell R. Oxytocin and oxytocin receptor expression in reproductive tissues of the male marmoset monkey. Biol Reprod. 1997;56:416–22. [PubMed] [Google Scholar]107. Arletti R, Bazzani C, Castelli M. Oxytocin improves male copulatory performance in rats. Horm Bev. 1985;19:14–20. [PubMed] [Google Scholar]108. Argiolas A, Collu M, d’Aquila P, Gessa GL, Melis MR, Serra G. Apomorphine stimulation of male copulatory behavior is prevented by the oxytocin antagonist d(Ch3)5Tyr(Me)-Orn8-vasotocin in rats. Pharmacol Biochem Behav. 1988;33:81–3. [PubMed] [Google Scholar]109. Ishak WW, Berman DS, Peters A. Male anorgasmia treated with oxytocin. J Sex Med. 2008;5:1022–4. [PubMed] [Google Scholar]110. Burri A, Heinrichs M, Schedlowski M, Kruger TH. The acute effects of intra-nasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology. 2008;33:591–600. [PubMed] [Google Scholar]111. Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15:373–7. [PubMed] [Google Scholar]112. Exton MS, Krüger TH, Koch M, Paulson E, Knapp W, Hartmann U, et al. Coitus-induced orgasm stimulates prolactin secretion in healthy subjects. Psychoneuroendocrinology. 2001;26:31–44. [PubMed] [Google Scholar]113. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, et al. Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction. J Sex Med. 2009;6:1457–66. [PubMed] [Google Scholar]114. Carani C, Isidori AM, Granata A, Carosa E, Maggi M, Lenzi A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005;90:6472–9. [PubMed] [Google Scholar]115. Corona G, Mannucci E, Petrone L, Fisher AD, Balercia G, Scisciolo G, et al. Psychobiological correlates of delayed ejaculation in male patients with sexual dysfunctions. J Androl. 2006;27:453–8. [PubMed] [Google Scholar]116. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. The relationship between premature ejaculation and hyperthyroidism. J Urol. 2009;181:1273–80. [PubMed] [Google Scholar]117. Cihan A, Demir O, Demir T, Aslan G, Comlekci A, Esen A. Investigation of the neural target level of hyperthyroidism in premature ejaculation in a rat model of pharmacologically induced ejaculation. J Sex Med. 2011;8:90–6. [PubMed] [Google Scholar]118. Corona G, Ricca V, Bandini E, Rastrelli G, Casale H, Jannini E, et al. SIEDY Scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction. J Sex Med. 2012;9:2017–26. [PubMed] [Google Scholar]119. Öztürk MI, Koca O, Tüken M, Keleş MO, Ilktac A, Karaman MI. Hormonal evaluation in premature ejaculation. Urol Int. 2011;88:454–8. [PubMed] [Google Scholar]120. Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH. Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction. J Sex Med. 2005;2:865–70. [PubMed] [Google Scholar]121. Rabb MH, Thompson DL, Barry BE, Colborn DR, Garza F, Hehnke KE. Effects of sexual stimulation, with and without ejaculation, on serum concentrations of, LH, FSH, testosterone, cortisol and prolactin in stallions. J Anim Sci. 1989;67:2724–9. [PubMed] [Google Scholar]122. Borg KE, Esbenshade KL, Johnson BH. Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar. J Anim Sci. 1991;69:3230–40. [PubMed] [Google Scholar]123. Bishop JD, Malven PV, Singleton WL, Weesner GD. Hormonal and behavioural correlates of emotional states in sexually trained boars. J Anim Sci. 1999;77:3339–45. [PubMed] [Google Scholar]124. Veronesi MC, Tosi U, Villani M, Govoni N, Faustini M, Kindahl H, et al. Oxytocin, vasopressin, prostaglandin F(2α), luteinizing hormone, testosterone, estrone sulfate, and cortisol plasma concentrations after sexual stimulation in stallions. Theriogenology. 2010;73:460–7. [PubMed] [Google Scholar]125. Veronesi MC, de Amicis I, Panzani S, Kindahl H, Govoni N, Probo M, et al. PGF(2α), LH, testosterone, oestrone sulphate, and cortisol plasma concentrations around sexual stimulation in jackass. Theriogenology. 2011;75:1489–98. [PubMed] [Google Scholar]126. Wildt DE, Phillips LG, Simmons LG, Chakraborty PK, Brown JL, Howard JG, et al. A comparative analysis of ejaculate and hormonal characteristics of the captive male cheetah, tiger, leopard, and puma. Biol Reprod. 1988;38:245–55. [PubMed] [Google Scholar]127. Brown JL, Wildt DE, Phillips LG, Seidensticker J, Fernando SB, Miththapala S, et al. Adrenal–pituitary–gonadal relationships and ejaculate characteristics in captive leopards (Panthera pardus kotiya) isolated on the island of Sri Lanka. J Reprod Fertil. 1989;85:605–13. [PubMed] [Google Scholar]128. Carani C, Bancroft J, Del Rio G, Granata ARM, Facchinetti F, Marrama P. The endocrine effects of visual erotic stimuli in normal men. Psychoneuroendocrinology. 1990;15:207–16. [PubMed] [Google Scholar]129. Krüger T, Exton MS, Pawlak C, von zur Mühlen A, Hartmann U, Schedlowski M. Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men. Psychoneuroendocrinology. 1998;23:401–11. [PubMed] [Google Scholar]130. Exton NG, Truong TC, Exton MS, Wingenfeld SA, Leygraf N, Saller B, et al. Neuroendocrine response to film-induced sexual arousal in men and women. Psychoneuroendocrinology. 2000;25:187–99. [PubMed] [Google Scholar]131. Ismail AA, Davidson DW, Loraine JA. Relationship between plasma cortisol and human sexual activity. Nature. 1972;237:288–9. [PubMed] [Google Scholar]132. Valassi E, Santos A, Yaneva M, Tóth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. J Endocrinol. 2011;165:383–92. [PubMed] [Google Scholar]133. Granata A, Tirabassi G, Pugni V, Arnaldi G, Boscaro M, Carani C, et al. Sexual dysfunctions in men affected by autoimmune addison’s disease before and after short-term gluco- and mineralocorticoid replacement therapy. J Sex Med. 2013;10:2036–43. [PubMed] [Google Scholar]134. Vignozzi L, Filippi S, Morelli A, Luconi M, Jannini E, Forti G, et al. Regulation of epididymal contractility during semen emission, the first part of the ejaculatory process: a role for estrogen. J Sex Med. 2008;5:2480. [PubMed] [Google Scholar]136. Rowe P, Comhaire F. WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge University Press; Cambridge: 2000. [Google Scholar]137. Finkelstein JS, Lee H, Burnett-Bowie SAM, Pallais JC, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22. [PMC free article] [PubMed] [Google Scholar]138. Corona G, Maggi M. The role of testosterone in erectile dysfunction. Nat Rev Urol. 2010;7:46–56. [PubMed] [Google Scholar]139. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004;145:2253–63. [PubMed] [Google Scholar]140. Swaab DF. Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab. 2007;21:431–44. [PubMed] [Google Scholar]

Here’s How Ejaculation Actually Works

Ejaculation may feel like a glorious mess, as uncontrollable as an avalanche or a runaway train. In reality, it’s a tightly choreographed court dance: integrating three different branches of the nervous system, triggering cascades of contractions in smooth and striated muscles, all accompanied by the electrical storm of orgasm. Here’s how it works.

Sexual Feedback

Ejaculation is the endpoint of a process that begins with a touch. Skin covering the shaft and glans of the penis is filled with nerve endings sensitive to pressure and vibration. Stroking that skin sends signals to the brain that say ‘sexytime!”

The brain bundles those signals into the gestalt of information that it’s getting from other parts of the body: eyes, nose, imagination, and if sexual arousal develops, it responds by making that penile skin even more sensitive to touch. More touching further increases sensitivity, in a positive feedback loop that can build to a show-stopping involuntary eruption.

When enough stimulation trips arousal over into orgasm, it also triggers a storm of activity in the three ejaculatory centers deep in the brain. These areas, in the hypothalamus and the midbrain, fire off a pattern of impulses to coordinate the release of sperm from the testes, the creation of semen, and tie the final contractions tossing semen out of the body to the feelings of orgasm.

G/O Media may get a commission

Catch more Z’s for less
Designed with some of the most advanced noise-canceling capabilities in the world, the Sleepbuds II have a soft, comfortable fit literally meant for falling asleep in.

Loading the Charge

Before the spurting can begin, sperm need to be brought out of storage and put in position. And despite the tails, they can’t yet swim for themselves.

Instead, smooth muscles in the walls of male reproductive organs contract in a coordinated wave. The conveyor-belt like movement takes concentrated masses of sperm from the epididymis where they matured and dumps them into the urethra at the base of the penis. Along the way, they pass by a series of glands (like the seminal vesicles and the prostate) which each squeeze out specialized fluids that dilute the sperm and create the complex goo we call semen.

Semen accumulates at the back end of the penis, inside the base of an erectile structure called the corpus spongiosum (or in older papers, the corpus cavernosum urethrae). The corpus spongiosum is the odd man out of the three erectile structures inside the penis: unlike the two erection-producing corpora cavernosa that run alongside it, the corpus spongiosum is softer and flares at its tip to form the glans. Its base also swells slightly, forming a structure called the urethral bulb.

The urethra plunges into the middle of the bulb in a sort of turducken of sexual tissues: urethra at the center, erectile tissue surrounding it, all wrapped in layers of muscle. As semen fills the urethra, pressure starts to build in the bulb. The muscular conveyor belt from the reproductive ducts keeps pushing more fluid forward, and the bladder prevents back-flow by sealing its opening into the urethra. (The fact that the bladder closes up shop is also why urine doesn’t spurt out at orgasm.)

With nowhere else to go, the semen inflates the urethral bulb like a water balloon. As the bulb swells to 2-3 times its normal diameter, it adds “I’m full” signals to the erotic mix.

The whole process–called emission–has taken about 3 seconds, and it’s been paired with a growing feeling of inevitability. Now we’re ready for the big finish.

Past the Point of No Return

This is the point at which wads are shot, loads are dropped, rocks are shot off. The euphemisms are telling: the main event–expulsion–is completely involuntary, a reflex run by the spinal cord, no brain input needed. And once it starts, it can’t be stopped.

The signal that tells male genitals the big moment has arrived comes from a group of neurons near the base of the spinal cord called Onuf’s nucleus. Once triggered, their signals take control of the muscles at the base of the penis and touch off a series of strong involuntary contractions.

One of the muscles in question, the bulbospongiosus (also called the bulbocavernosus in old texts), surrounds the entire urethral bulb and the rear of the corpus spongiosum. A second surrounds the urethra proper. Together, they form a muscular pump that can throw semen out of the body with a surprising amount of force.

When the right signal arrives, the pumping starts. Both muscles contract together rhythmically, raising the pressure in the urethral bulb in pulses and pushing semen through the urethra in spurts. Each high pressure push is followed by a short period of relaxation which lets the urethral bulb refill with semen. Sensory feedback from the pulsed contractions tie into (and may intensify) the brain’s orgasmic cascades.

The pressure change in the urethral bulb is substantial: each contraction also creates sympathetic pressure peaks in the blood inside the erect corpus spongiosum. The first few squeezes are so forceful that semen doesn’t simply travel the 5 to 6 inches of the penile urethra to its opening in the glans–the first few spurts can fly one to two feet through the air beyond it.

The muscles follow up the first three or four strong contractions with several seconds of slower, weaker pulses, moving between 2 to 5 milliliters of semen to the outside world. Once that’s done, at least for a while, all that’s left is the mopping up.

[Purohit and Beckett 1976 | Shafik 1995 | Keast 1999 | Giuliano and Clement 2005 | Schober and Pfaff 2007 | Sengelaub and Forger 2008 | Jones and Lopez 2014 | Puppo and Puppo 2015]

Top image GPS via Flickr | CC BY 2.0; other images Henry Vandyke Carter from Gray’s Anatomy (1918) via Wikimedia


Contact the author at [email protected].

Ejaculation – an overview | ScienceDirect Topics

Ejaculation potential following SCL

Ejaculation potential following SCL is similarly affected by the level and completeness of the lesion (Bors and Comarr, 1960; Comarr, 1970; Chapelle et al., 1980; Courtois et al., 1993b, 1999; Biering-Sørensen and Sønksen, 2001; DeForge et al., 2006; Elliot, 2006; Everaert et al., 2010). Higher lesions to the cervical or thoracic spinal segments maintain all reflexes below the lesion, including multisegmental reflexes. Reflex ejaculation is therefore possible.

Studies support this neurologic prognosis, as observations as early as 1948, and throughout the 1960s and later show some ejaculation potential (Munro et al., 1948; Talbot, 1949, 1955; Bors and Comarr, 1960; Comarr, 1970; Courtois et al., 1993b, 1995, 1999; Everaert et al., 2010). Although ejaculation is possible through preservation of the multisegmental reflex, the literature indicates that the natural occurrence of ejaculation is rather infrequent (DeForge et al., 2005; Courtois et al., 2008a; Chéhensse et al., 2013). Earlier studies have shown that ejaculation was relatively rare (5–15%) in men with SCL when using natural stimulation (e.g., masturbation, intercourse) (Munro et al., 1948; Bors and Comarr, 1960; Comarr, 1970), but later studies on vibrostimulation (Brindley, 1981a; Szasz and Carpenter, 1989; Sønksen et al., 1994; Brackett et al., 1998, 2010a; Brackett, 1999) indicated that using stronger stimulation parameters, especially of higher amplitude (Sønksen et al., 1994, 1996; Ohl et al., 1996; Fode et al., 2012), significantly increased the success rate for ejaculation. The combination of natural and vibrostimulation in men with higher lesions further increases the potential for men with higher lesions to over 90% (Brackett and Lynne, 2000; Courtois et al., 2008a, b). It is noteworthy that ejaculation in men with SCL can go, and often does go, unnoticed as a result of retrograde ejaculation, which can result from bladder sphincter dyssynergia (typical in men with higher lesions) or opening of the bladder neck (lower lesions) (Chen et al., 1999; Sipski et al., 2006; Courtois et al., 2009b, 2013b). The assessment of remaining sexual function in men with SCL therefore requires paying attention to retrograde ejaculation in addition to anterograde ejaculation in order to conclude on true ejaculation potential.

While lesions to the TL spinal segments (Fig. 13.1) maintain reflex erection, the spinal connections between the sacral and TL pathways are generally lost, leading to anejaculation (except for incomplete lesions or lesions at T11–12, which may spare some lumbar fibers) (Comarr, 1970; Courtois et al., 1993b, 1995; Everaert et al., 2010).

Lesions to lower sacral segments (Fig. 13.1) impair reflex activity (Bors and Comarr, 1960; Comarr, 1970; Courtois et al., 1993b, 1995, 1999; Everaert et al., 2010). Reflex ejaculation is therefore lost, but psychogenic ejaculation, often referred to as dribbling ejaculation, is reported (Kuhr et al., 1995; Courtois et al., 2013c). These dribbling ejaculations, which are often indistinctly associated with lumbosacral lesions in the literature (hence failing to distinguish epiconus, conus, or cauda equina lesions), are also described as extremely premature (e.g., upon a mere sexual thought), a condition which appears following SCL in men who otherwise controlled their ejaculation prior to injury.

As mentioned before, lesions to the cauda equina present a special case where the extent of the damage can largely vary. Special attention is therefore required to assess remaining sexual function.

Ejaculation: What to Expect As You Age

There is little written on ejaculatory issues aside from timing problems (premature and delayed ejaculation) and hematospermia (blood in the semen). However, not a day goes by in my urology practice where I do not see at least several patients who complain about declining ejaculation function.

What does the word ejaculation mean?

Ejaculation derives from ex, meaning out + jaculari, meaning to throw, shoot, hurl, cast.

Trivia: You do not need an erection to ejaculate and achieve an orgasm. A limp penis cannot penetrate, but is very capable of ejaculation and orgasm. 

What happens to ejaculations as we age?

Ejaculation and orgasm often become less intense, with diminished force, trajectory and volume. What was once an intense climax with a substantial volume of semen that could be forcefully ejaculated gives way to a lackluster experience with a small volume of semen weakly dribbled out the penis. 

So what’s the big deal?

Men don’t like meager, lackadaisical-quality ejaculations and orgasms. Sex is important to many of us and getting a good quality rigid erection is foremost, but the culmination—ejaculation and orgasm—is equally vital. We may be 40 or 50 years old, but we still want to point and shoot like we did when we were 20. As the word origin indicates, we want to be able to shoot out, hurl or cast like an Olympian and we want that intensely pleasurable feeling of yesteryear.

The science of ejaculation

Sexual climax consists of three phases—emission, ejaculation, and orgasm. When the intensity and duration of sexual stimulation surpasses a threshold, emission occurs, in which secretions from the prostate gland, seminal vesicles, epididymis, and vas deferens are deposited into the urethra within the prostate gland. During ejaculation the pelvic floor muscles contract rhythmically, sending wave-like contractions rippling down the urethra to forcibly propel the semen in a pulsating and explosive eruption. Orgasm is the intense emotional excitement that accompanies the physical act of ejaculation.  

Big head versus little head

Ejaculation is an event that takes place in the penis; orgasm occurs in the brain.

The process of emission and ejaculation is actually a very complex and highly coordinated neurological event involving several specific centers in the brain (amygdala, thalamus and other areas), spinal cord and peripheral nervous system.

What makes up the love juices?

Less than 5% of the volume of semen is actually sperm and the other 95+% is a cocktail of genital juices that provides nourishment, support and safekeeping for sperm. 70% of the volume comes from the seminal vesicles, which secrete a thick, viscous fluid and 25% from the prostate gland, which produces a milky-white fluid. A negligible amount is from the bulbo-urethral glands, which release a clear viscous fluid (pre-come) that has a lubrication function. 

What’s normal volume?

The average ejaculate volume is 2-5 cc (one teaspoon is the equivalent of 5 cc).  While a huge ejaculatory load sounds like a good thing, in reality it can cause infertility. The sperm can literally “drown” in the excessive seminal fluid. 

Why does the seminal tank dry with aging?

As men get older, there are changes in the reproductive organs, particularly the prostate gland, one of the few organs in the body that enlarges with age.

The aging prostate and seminal vesicles produce less fluid; additionally the ducts that drain the genital fluids can become clogged. In many ways, the changes in ejaculation parallel the changes in urination experienced by the aging male. Certain medications that are used to treat prostate enlargement profoundly affect ejaculatory volume. Additionally, the pelvic floor muscles—which play a vital role in ejaculation—weaken with aging. 

What about the pelvic floor muscles?

The pelvic floor muscles play a key role in ejaculation. The bulbocavernosus muscle (BC) is the motor of ejaculation, that which supplies the “horsepower.” The BC surrounds the inner, deepest portion of the urinary channel. It is a compressor muscle that during sex engorges the spongy erection chamber that surrounds the urethra and engorges the head of penis. At the time of climax, the BC expels semen by virtue of its strong rhythmic contractions, allowing ejaculation to occur and contributing to orgasm.

A weakened BC muscle may result in semen dribbling with diminished force or trajectory, whereas a strong BC can generate powerful contractions that can forcibly ejaculate semen at the time of climax.

How to get the juices flowing again?

Pelvic floor muscle training can be a useful tool to improve ejaculation. The stronger the BC, the higher the ejaculatory horsepower and the better the capacity for engorgement of the erection chamber that envelopes the urethra, resulting in optimized urethral pressurization and ejaculation. The intensified ejaculation resulting from a robust BC can enhance the orgasm that accompanies the physical act of ejaculation.

Written by Dr. Andrew Siegel


90,000 What are the ejaculatory ducts?

Ejaculatory ducts are a pair of tubular anatomical structures in the male reproductive system that transport sperm from the vas deferens to the penis during ejaculation. These ducts are less than an inch long and are formed by the confluence of two other duct systems of the male reproductive system, the vas deferens and the excretory ducts of the seminal vesicles. The ejaculatory ducts are located at the base of the prostate gland.Blockage or obstruction of the ejaculatory duct can lead to conditions such as inability to produce sperm, low sperm count, and male infertility.

The ejaculatory ducts are sometimes considered accessory glands of the male prostate. Their structure includes a thin, coarse and fibrous outer layer that is practically non-existent by the time the ducts enter the prostate. Inside the fibrous outer layer are layers of muscle tissue and mucous membrane.The canals narrow as they pass through the prostate gland and end in a pair of small slit holes. These openings are connected to a small raised area called the seminal colliculus, which in turn connects to a fold of tissue at the back of the urethra called the urethral crest.

Sperm is produced in the male testicles and is stored in the left and right epididymis. Before ejaculation occurs, the sperm must pass into the ducts of the vas deferens.During ejaculation, undulating, involuntary muscle contractions push sperm from the vas deferens into the ejaculatory ducts through a process called peristalsis. The ejaculatory ducts transport sperm to the urethra, collecting other sperm components from the seminal glands, bulbourethral glands, and finally the prostate gland. Sperm drains from the ejaculatory duct into the seminal colliculus, then passes through the urethra and leaves the body through the tip of the penis.

Ejaculatory duct obstruction (EDO) is a relatively rare condition, resulting in approximately 1-5 percent of male infertility.It is usually caused by a previous urinary tract infection or surgical procedures performed on the bladder, urethra, prostate, or related structures. Symptoms of EDO include infertility, an extremely low sperm count called azoospermia, or low sperm volume, called oligospermia, or no sperm at all, called aspermia, and pelvic pain, especially after ejaculation. Invasive urologic EDO reversal surgery, called transurethral resection of the prostate, is one of the existing treatments.

OTHER LANGUAGES

90,000 Women and men of reproductive age | Reproductive health and reproductive rights

Reproduction (reproduction) is a process in which two organisms are necessarily involved – a female and a male, therefore, the concept of reproductive health applies to representatives of both sexes equally. A man is an equal participant in the reproductive process. In addition, men have no less problems leading to loss of reproductive health than women.Few people know that a man is the culprit in 40% of sterile marriages.

A man’s ability to reproduce depends on the usefulness of two functions – spermogenesis (the process of sperm formation) and sexual potency (the ability to have sexual intercourse, the presence of an erection). Violation of each of these functions individually or a combination of impotence (erectile dysfunction) and spermogenesis pathology (qualitative and / or quantitative changes in sperm) is the main cause of reproductive health disorders in men.

The male reproductive system is more susceptible to the action of harmful environmental factors than the female, therefore, great attention must be paid to the health of a boy, a young man, a man. So, let’s take a look at the male reproductive system.

The following specialists deal with issues of male reproductive health:

  • andrologist
  • urologist
  • family doctor
  • Dermatologist-Venereologist.

Male reproductive system

Male reproductive organs ensure the birth, maturation and delivery of sperm to the woman’s vagina, where the process of fertilization and further development of the fetus takes place.

Unlike the female reproductive system, most of the organs of the male reproductive system are located outside the body, which makes it more vulnerable.

Male genital organs are divided into:

  • external organs:
    • penis (penis),
    • scrotum,
    • 90,023 testicles.

  • internal organs:
    • epididymis,
    • vas deferens,
    • ejaculatory (ejaculatory) ducts,
    • urethra,
    • seminal vesicles,
    • prostate gland (prostate),
    • Bulburetal glands.

Penis

This is a male organ, consisting of 3 parts: a root, which is attached to the wall of the abdomen; body or rod; and the glans, which is the tapered portion at the end of the penis. The head of the penis is covered with a loose layer of skin called the foreskin. The urethral opening, the tube that transports semen and urine, is at the end of the penis.

Scrotum

This is a loose pouch of leather that sits behind the penis.It contains the testes as well as many nerves and blood vessels. The scrotum acts as a “climate control system” for the testicles. For normal sperm production, testicular temperature should be slightly lower than body temperature. Special muscles in the wall of the scrotum allow it to tense and relax, moving the testicles closer to the body when they need to be warm and moving them away from the body to lower the temperature

Testicles

These are the oval organs that lie in the scrotum, attached at the ends by a structure called the spermatic cord.The testicles are responsible for the production of testosterone, the main male sex hormone, and for the production of sperm. Inside the testicles are many convoluted tubules called seminiferous tubules. These tubes are responsible for the production of sperm

Epididymis

This is a long, curved tube that sits on the back of each testicle. It transports sperm and stores the sperm that are produced in the testes. The epididymis is also responsible for the maturation of sperm, since the sperm that comes out of the testicles is immature and unable to fertilize.During sexual arousal, as a result of contractions, sperm passes into the vas deferens

Vas deferens

This is a long muscular tube that runs from the epididymis into the pelvic cavity, just behind the bladder. The vas deferens, in preparation for ejaculation, transport mature sperm into the urethra, the tube that carries urine or semen outside the body.

Ejaculating ducts

They are formed due to the fusion of the vas deferens and seminal vesicles.The ejaculatory ducts are emptied into the urethra.

Urethra

This is the tube that carries urine from the bladder to the outside of the body. In men, it has the additional function of ejaculating seminal fluid at the time a man reaches orgasm. When the penis is erect during sex, the flow of urine from the urethra is blocked and only semen can be ejected during orgasm.

Seminal vesicles

These are sacs that attach to the vas deferens near the base of the bladder.The seminal vesicles produce a sugar-laden fluid (fructose), which is the energy source for the sperm, allowing them to move. The seminal vesicle fluid makes up most of the volume of a man’s ejaculatory fluid or ejaculate.

Prostate

Located below the bladder in front of the rectum. The prostate gland brings additional fluid into the ejaculate. Prostate fluid also helps fuel sperm. The urethra, which carries ejaculate during orgasm, passes through the center of the prostate gland.

Bulburetal glands

These are glands, also called Cooper’s glands, located on the sides of the urethra, just below the prostate gland. These glands produce clear fluid that flows directly into the urethra and serves to lubricate the urethra and neutralize any acidity that may be in the urethra due to residual urine droplets.

Functioning of the male reproductive system

As in the female body, hormonal regulation is the basis for the functioning of the male reproductive system.One of the higher departments of hormonal regulation of male reproductive function is the hypothalamus – a region of the brain, in the nuclei of which a specific hormone gonadoliberin is produced, which stimulates the pituitary gland, which in turn is responsible for the production of male hormones, namely:

  • follitropin (follicle-stimulating hormone – FSH), which is necessary for the production of sperm (spermogenesis) and is the main stimulator of the growth of the vas deferens and the formation of sperm;
  • lutropin (luteinizing hormone – LH), which is necessary for spermogenesis, and it also stimulates the formation of testosterone in the testes;
  • testosterone, which is responsible for the formation of male sexual characteristics and maintenance of the reproductive function, in particular:

    • Formation and growth of male genital organs;
    • Manifestation of secondary sexual characteristics
      • male pattern hair growth
      • enlarged larynx
      • the vocal cords thicken (the tone of the voice decreases)
    • Manifestation of normal sex drive (libido)
    • stimulating effect on muscle growth and whole body growth

At the time of birth, the testosterone level in boys is slightly higher than in girls, rises rapidly after birth, decreases by the first year of life and remains low until adolescence, and increases during adolescence.From 17 to 60 years of age, its level is almost constant, gradually decreasing from 60 years.

(PDF) Overcoming difficulties in achieving orgasm and psychotherapy of its disorders

J. Jacobson [29, 32, 49], systematic desensitization according to Wolpe

(J. Wolpe) [14, 59, 60], developed by us a method of correcting behavioral programs

[17, 24], adapted and modified by us for the treatment of sexual disorders

processing by eye movements ”[20, 35].

When using hypno-suggestive programming, formulas are used

aimed at cultivating (intensifying) voluptuous sensations in the

preliminary and main periods of intercourse, as well as a steady increase in

sexual arousal during coitus, ending with discharge. Hypnosuggestational

modeling consists in evoking in patients those psychophysiological

reactions that usually occur during the full natural course of

sexual intercourse.This technique is more complex than hypnosuggative programming,

requires knowledge of the psychophysiology of sexual intercourse and detailed acquaintance with

features of the reactions of a particular person during intercourse before and after

the onset of the disorder. Treatment is carried out in the form of individual sessions, more than

longer than with hypnosuggestational programming. In addition, with

modeling in clinical sexology, doctors also face ethical difficulties

.Here are a number of descriptions of the successful application of hypnosuggestational

modeling in sexual dysfunctions in women [9, 12].

Richardson (1964) reports the recovery of 72 out of 76 women treated with hypnosis

for “sexual failure”. In cases of anorgasmia, the patient was indoctrinated with

corresponding hallucinations: she saw her husband, had sexual intercourse with him

. At the same time, various reactions of women to sexual stimulation were noted.

With the help of suggestion, they were controlled until the onset of orgasm [12].

Interesting data is provided by S. Kratochvíl (1969), who considers

the possibility of using hypnotherapy in the treatment of women suffering from decreased libido

and anorgasmia. Based on the treatment of 5 women, the author concludes that

intercourse and orgasm in hypnosis can be either hallucinations or

role-playing.In this case, the behavior can be different. Sometimes it resembles

behavior before and during intercourse: the patient talks with her husband,

makes appropriate movements with her arms and body, including extending her hips,

moving her pelvis. In other cases, the woman remains motionless and only the words

addressed to her husband indicate her sexual experiences. In a number of cases,

, no physiological reactions were noted, but the experiences caused by

Neurology – medical unit No. 8 Serpukhov

Neurology (the outdated nomenclature name is neuropathology) is a science that is a set of biomedical directions that studies the nervous system, its regularities development, structure and functioning in health and disease, as well as the development of methods for the diagnosis, treatment and prevention of nervous diseases.

Given the interdependence of the nervous system and various organs and systems, there are a number of borderline disciplines at the junction of neurology and other branches of medicine:

  • vertebroneurology or neuro-orthopedics (neurological complications in pathologies of the musculoskeletal system, primarily the spine),
  • neurosurgery (surgical treatment of neurological diseases),
  • otoneurology (pathologies of coordination, hearing and smell, as well as impaired speech and swallowing),
  • neuroophthalmology (vision pathologies caused by damage to the pathways and analyzers of the nervous system),
  • neuroendocrinology (disorders of the nervous system in pathology of the endocrine glands and vice versa),
  • angioneurology (disorders of the nervous system in pathology of the cardiovascular system),
  • neuroinfections (damage to the nervous system during infectious processes),
    psychoneurology (reactive states, somatoform disorders, behavior disorders).

Therefore, in relation to patients who turn to a neurologist, a systemic integrated approach with the involvement of various specialists in related fields of medicine and their close interaction is especially important.

The more acute the condition and the more intense the symptoms, or the more they increase over time, the faster it is necessary to consult a neurologist.

Before the appointment, it is advisable to prepare by putting in order the complaints, the probable causes of their occurrence, dependence on external factors, building the chronology of the development of the disease, previous injuries and diseases, their possible connection with the current state, and do not forget to take with you the conclusions of previous consultations, examinations ( including pictures) and recommendations for treatment (it is important to inform the doctor about the degree of its effectiveness).

In what situations should you contact a neurologist? In cases where the following complaints are concerned:

  • Violation of the motor sphere: muscle weakness (especially in certain limbs or facial muscles, growing, or paroxysmal, up to falls), increased muscle tone (constant, increasing, or paroxysmal (convulsions), up to spasms, in certain parts of the muscle or in the entire musculature), a decrease in muscle volume (especially in individual muscles or limbs), involuntary movements (uncontrolled twitching or obsessive movements, trembling of the limbs and / or head), depletion of movements (primarily facial expressions, gestures and auxiliary or coordinating movements, for example, when walking), impaired coordination (instability of posture, gait, especially with closed eyes).
  • Violation of the sensitive sphere: increased sensations (first of all, these are pains of various localization, including headaches, especially in certain situations, postures, movements, as well as increased sensitivity to certain influences), decreased sensations (up to numbness, especially in certain parts body), changes in sensations (burning, tingling and other previously unfamiliar sensations, impaired recognition of objects by touch, altered sensitivity to certain influences, for example, temperature), impaired taste (decrease, increase or perversion, especially in certain parts of the tongue), impaired sense of smell (especially on the one hand), hearing impairment (including noise, dizziness, nausea), visual impairment (decrease, the appearance of a veil, points (“flies”), spots in front of the eyes, loss of visual fields, double vision, drooping of the eyelid and the difference pupils).
  • Violation of the autonomic nervous system: changes in blood pressure (low, up to fainting; high, up to headaches; unstable, not associated with the pathology of the cardiovascular system and other internal organs), pain and other sensations in the heart (fading, increased palpitations, interruptions in the work of the heart, with no identified cardiac pathology, pathology of the chest and organs inside it), respiratory failure (shortness of breath, feeling short of breath, rapid breathing, coughing not associated with pathology of the respiratory system), indigestion (com in the throat; discomfort, up to pain, in the abdomen; belching, nausea and vomiting; increased stool, up to incontinence, delay, up to constipation, or increased urge not associated with the pathology of the gastrointestinal tract), urination disorder (increased frequency , including at night, up to incontinence), changes in the skin and its derivatives (pallor, cyanosis, redness, “marbling” , sweating, dry skin and mucous membranes, hair loss, brittle nails, not associated with dermatological or therapeutic diseases), impaired thermoregulation (increase or decrease in temperature, chills, not associated with infectious processes and inflammation), panic attacks (attacks of unreasonable anxiety, accompanied by various above fears and not associated with the pathology of the endocrine glands), sexual dysfunction (dysfunction of erectile and ejaculatory function, not associated with urological and psychiatric pathology).
  • Violation of higher nervous activity: impaired consciousness (agitation, depression, confusion, dullness), sleep disturbance (falling asleep, waking up, maintaining sleep, daytime sleepiness and other sleep problems), disorientation (in one’s own personality, space, time), disturbance attention (distraction), impaired memory (short-term and long-term), impaired speech (both understanding and reproduction, including counting, reading and writing), impaired recognition (people, objects, names, concepts), impaired purposeful acts (actions carried out at their own request and / or at someone’s request).

The team of neurologists of the medical-sanitary unit No. 8 sees its main tasks in providing qualified medical care to patients with various diseases of the nervous system. Patients with chronic cerebral ischemia, the consequences of cerebral circulation disorders, traumatic brain injury, patients with Parkinson’s disease, multiple sclerosis, after neurosurgical interventions (removal of herniated discs, removal of tumors), exacerbation of other chronic diseases of the spine and …The main principle of our employees’ work is an integrated approach to the diagnosis and treatment of diseases of the nervous system, and, importantly, the individual characteristics of each patient are taken into account. We make extensive use of all the possibilities we have to restore the patient’s health.

Ejaculatory dysfunction in men with prostate adenoma

A group of American urologists has published a comprehensive review in the journal Current Urology Reports that reflects current knowledge of the relationship between prostatic hyperplasia (BPH), lower urinary tract symptoms (LUTS) and ejaculatory dysfunction (ED).In contrast to erectile dysfunction in BPH, ED against the background of this pathology and appropriate treatment has been much less studied. Meanwhile, EJP is observed in 31-68% of men with LUTS associated with BPH.1 For the medical assessment of ejaculation, parameters such as frequency, volume, strength of ejaculation, time to ejaculation, the presence of pleasure, sensations of dryness and pain are used.2 Accordingly, the concept “Ejaculatory dysfunction” encompasses clinical phenomena such as premature ejaculation, delayed ejaculation, lack of ejaculation (anejaculation), painful ejaculation, and retrograde ejaculation.3 The severity of LUTS correlates with the severity of ED. On the other hand, according to one study, up to 70% of men tend to refuse treatment for BPH / LUTS if the side effect is ED. Thus, ED is an important issue to consider in the management of any patient with BPH / LUTS.

For patients with a total IPSS score <7, in whom LUTS do not cause anxiety and do not affect their quality of life, observation tactics are recommended.4,5 It involves limiting the volume of liquids, drinking caffeinated and alcoholic beverages, and refusal from taking cholinergic drugs.With this approach, 10% of patients note an improvement in sexual function, and 6% - a decrease.4 In any case, this tactic in some cases allows you to postpone the appointment of other methods of treatment.

Alpha-blockers, one of the first line therapies for BPH, although they appear to have overall beneficial effects on sexual function, their effect on ejaculatory function varies. It should be borne in mind that different drugs of this class have different affinities for adrenergic receptors.Tamsulosin and silodosin selectively act on alpha-1b-adrenergic receptors, which are present mainly in the lower urinary tract, which minimizes adverse reactions such as hypotension and dizziness, mediated by alpha-1b-adrenergic receptors in blood vessels and other tissues. A number of epidemiological studies have shown that ejaculation disorders associated with alpha-blockers usually include retrograde ejaculation and anejaculation, 6 however, their effect on ejaculatory function is based on the suppression of the emission phase: the muscles of the seminal vesicles, the vas deferens, the perineum, which provide it, are simply do not receive the proper electrical impulse from blocked alpha 1a receptors.7 The frequency of ED while taking tamsulosin depends on the dose of the drug. In patients taking 0.4 mg of tamsulosin per day, ejaculation disorders develop in 6% of cases, and a dose of 0.8 mg / day leads to ED in 18% of patients.8 Silodosin causes ED in 22-28% of patients. At the same time, the sensation of orgasm, as a rule, persists, and only 2.8% of patients discontinue therapy due to ED.8,9 However, the explanation of the effect of alpha-blockers on ejaculatory function is only hypothetical, and this phenomenon needs further study.This is indicated by the data that alfuzosin, which has an even more selective affinity for alpha-1a-adrenergic receptors, does not cause ED10 at all and may even reduce its manifestations13. Doxazosin and terazosin non-selectively block both alpha-1- and alpha-1b-adrenergic receptors. When compared with placebo, it has been shown that they do not affect ejaculatory function and libido7,8, but cause a decrease in blood pressure and therefore are contraindicated in patients with hypotension.

5-alpha-reductase (I5AR) inhibitors prevent the transformation of testosterone into dihydrotestosterone, which is a more potent androgen than its predecessor and is responsible for the growth and development of the prostate gland.Drugs in this class include dutasteride, a type 1 and type 2 5-alpha reductase inhibitor, and finasteride, which inhibits only a type 2 enzyme that dominates the prostate. Dutasteride reduces serum dihydrotestosterone levels by 90%, and finasteride – by 80% .11.7 EDI is observed in 4.7% of patients taking dutasteride, and 3.6% – on the background of finasteride.12 Interestingly, in a number of studies, long-term the use of I5ARs led to a decrease in their negative effect on sexual function, 11 while finasteride was more likely to cause sexual dysfunction than other drugs used to treat BPH, in particular, it led to ED more often than terazosin.11 Alpha-blockers and I5ARs are most effectively used in combination, and their optimal effect is given by their appointment in patients with moderate to severe LUTS and prostate volume over 25 ml. 5

Inhibitors of phosphodiesterase type 5 (IF5) inhibit the breakdown of cGMP in the corpus cavernosum of the penis, which leads to an increase in the intracellular concentration of calcium and nitric oxide, causing additional relaxation of smooth muscles in erectile tissues and, as a result, to the flow of blood into them.Drugs of this class (tadalafil, sildenafil, avanafil, vardenafil, udenafil) are indicated for erectile dysfunction. In patients with BPH / LUTS, they decrease the total IPSS score, increase the total score on the International Erectile Function Scale (IIEF), and thus improve their quality of life.27 The most pronounced improvements are recorded in severe LUTS. Although the mechanism of the beneficial effect of these funds on ejaculatory function is not yet clear, it is assumed that it is a consequence of, among other things, an improvement in erection.28 There is evidence of the efficacy of IF5 in premature ejaculation, 27 although further research is clearly needed in this area. Combination therapy with alpha-blockers has an advantage over monotherapy for each drug class.13

Since LUTS associated with BPH include symptoms of an overactive bladder (increased and increased urge to urinate, nocturia), the appointment of beta-3-agonists and anticholinergic drugs that relax smooth muscles is justified.Although beta-3 receptors have also been found in the corpus cavernosum14-16, the effect of beta-3-agonists on this tissue is still unknown and needs to be investigated. Patients who received the anticholinergic tolterodine for LUTS / BPH against the background of ineffectiveness of alpha-blockers noted improvement in the symptoms of emptying, an increase in the IIEF score by an average of 6.9 points, in the absence of complaints of ED.17 Surgical treatment of LUTS / BPH is associated with the highest risk of erectile and ejaculatory dysfunction, 18 therefore it is recommended to reserve it for patients with moderate to severe symptoms who have failed other therapies.In recent years, the popularity of transurethral resection of the prostate (TURP) has declined, as other innovative methods of intervention appear. According to clinical studies, after TURP men do not notice changes in the side of such a symptom as painful ejaculation, while the incidence of ED in general after TURP is higher than before surgery.19,20 Monopolar and bipolar TURP do not differ in their effect on sexual function.21 Photoselective vaporization of the prostate with a green laser is often regarded as an alternative to TURP, since it is associated with less blood loss and the duration of postoperative hospitalization.22 It has been shown that the average decrease in the IPSS score after this type of intervention is 13 points23, but 30% of patients have retrograde ejaculation26, and 5.4% have painful ejaculation.24 Despite ED, the overall assessment of sexual function and patients increases. 23 Enucleation and ablation of the prostate gland with holmium laser results in a decrease in IPSS by an average of 12 points. After laser enucleation, 21% of patients experience pain or discomfort during ejaculation, and in 70% of patients 6 months after the intervention, retrograde ejaculation takes place while maintaining orgasm.20.10 The frequency of retrograde ejaculation after laser ablation is slightly lower – 31.1% .24

Minimal invasive interventions are increasingly used because they can significantly alleviate symptoms with a lower risk of sexual dysfunction. These include transurethral microwave thermotherapy (TUMT) and transurethral needle ablation (TUNA). Immediately after TUMT, 19.3% of patients complain of ED, and after 24 months – 11% .27 After TUNA, ED is noted much less frequently – in 5.6% of patients.27 UroLift® is a new minimally invasive technique that allows you to “expand” the urethra and prostate lobes using implants. This gives a decrease in the IPSS score by an average of 10.8 points, increases the ability to ejaculate by 4%, ejaculatory power by 23%, and ejaculate volume by 22% .18 At the same time, the procedure itself does not lead to retrograde ejaculation and other forms of ED. .28

Among the “methods of the future”, the authors mention steam ablation of the prostate and PRX302 therapy. The latter drug is a protein activated by a prostate-specific antigen; after injection of PRX302 into the transition zone, it creates special pores in the cells of the prostate gland, through which the cell contents leak, as a result of which the cells die.This results in significant relief of LUTS (mean 9 points in IPSS) with no systemic effects at all.29 The effect of these methods on ejaculatory function is not yet known.

In conclusion, the authors draw the following conclusions: the first line of treatment for LUTS due to BPH is pharmacotherapy; the incidence of EDP in its background varies from 18% when using alpha-blockers to <2% when using I5AR, while IF5 even improves ejaculatory function. ED in surgical treatment of BPH has a frequency of 30% to 75%.Apparently, the future lies with minimally invasive interventions and innovative treatment methods.

Literature
1. van Dijk MM et al. Effects of alpha (1) – adrenoceptor antagonists on male sexual function. Drugs. 2006; 66: 287-301. New Zealand.
2. Kim MK et al. An open, non-comparative, multicenter study on the impact of alfuzosin on sexual function using the Male Sexual Health Questionnaire in patients with benign prostate hyperplasia. Int J Clin Pract.2010; 64: 345-50. England.
3. Gacci M et al. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. J Sex Med. 2014; 11 (6): 1554–66. This is a great article that covers many of the side effects and concerns with the medications dealing with ejaculatory dysfunction in LUTS / BPH.
4. Gacci M et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia.Eur Urol. 2011; 60 (4): 809-25.
5. Nix JW, Carson CC. Medical management of benign prostatic hypertrophy. Can J Urol. 2007; 14 Suppl 1: 53-7.
6. Yoshimura K et al. A survey of the FAERS database concerning the adverse event profiles of alpha1-adrenoreceptor blockers for lower urinary tract symptoms. Int J Med Sci. 2013; 10 (7): 864-9.
7. Welliver C et al. Impact of alpha blockers, 5-alpha reductase inhibitors and combination therapy on sexual function. Curr Urol Rep. 2014; 15 (10): 441. This is another great paper dealing with all different types of sexual side effects of LUTS / BPH.23.
8. Yokoyama T et al. Effects of three types of alpha-1 adrenoceptor blocker on lower urinary tract symptoms and sexual function in males with benign prostatic hyperplasia. Int J Urol. 2011; 18 (3): 225-30.
9. Sakata K, Morita T. Investigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia. BMC Urol. 2012; 12: 29.
10. Giuliano F. Impact of medical treatments for benign prostatic hyperplasia on sexual function. BJU Int. 2006; 97 Suppl 2: 34-8. discussion 44-5.
11. Erdemir F, Harbin A, Hellstrom WJ. 5-alpha reductase inhibitors and erectile dysfunction: the connection. J Sex Med. 2008; 5 (12): 2917-24.
12. Kaplan SA et al. A 5-year retrospective analysis of 5alphareductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride. Int J Clin Pract. 2012; 66 (11): 1052-5.
13. Uckert S et al. Phosphodiesterase inhibitors in clinical urology.Expert Rev Clin Pharmacol. 2013; 6 (3): 323–32.
14. Cirino G et al. Involvement of beta 3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavernosum function. Proc Natl Acad Sci U S A. 2003; 100: 5531-6. United States.
15. Matsumoto R et al. Expression and functional role of beta3 – adrenoceptors in the human ureter. Int J Urol. 2013; 20 (10): 1007-14
16. Nomiya M, Yamaguchi O. A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders.J Urol. 2003; 170 (2 Pt 1): 649-53.
17. Kaplan SA et al. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol. 2005; 174: 2273-5. discussion 2275-6.
18. McVary KT et al. Treatment of LUTS secondary to BPH while preserving sexual function: randomized controlled study of prostatic urethral lift. J SexMed. 2014; 11 (1): 279–87.
19. Hellstrom WJ et al. Ejaculatory dysfunction and its association with lower urinary tract symptoms of benign prostatic hyperplasia and BPH treatment.Urology. 2009; 74 (1): 15–21.
20. Zong HT et al. The impact of transurethral procedures for benign prostate hyperplasia on male sexual function: a meta-analysis. J Androl. 2012; 33 (3): 427–34.
21. Mamoulakis C et al. Bipolar vsmonopolar transurethral resection of the prostate: evaluation of the impact on overall sexual function in an international randomized controlled trial setting. BJU Int. 2013; 112 (1): 109–20.
22. Bruyere F. The relationship between photoselective vaporization of the prostate and sexual function.Curr Urol Rep. 2011; 12 (4): 261–4. Curr Urol Rep (2016) 17:48 Page 7 of 8 48 90 301 23. Terrasa JB et al. Prospective, multidimensional evaluation of sexual disorders in men after laser photovaporization of the prostate. J Sex Med. 2013; 10 (5): 1363–71.
24. Elshal AM et al. Male sexual function outcome after three laser prostate surgical techniques: a single center perspective. Urology. 2012; 80 (5): 1098-104.
25. Meng F et al. Change of sexual function in patients before and after Ho: YAG laser enucleation of the prostate.J Androl. 2007; 28 (2): 259–61.
26. Spaliviero M et al. Does Greenlight HPS (™) laser photoselective vaporization prostatectomy affect sexual function? J Endourol. 2010; 24 (12): 2051-7.
27. Frieben RW et al. The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review. Asian J Androl. 2010; 12: 500-8. China.
28. Woo HH et al. Preservation of sexual function with the prostatic urethral lift: a novel treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia.J Sex Med. 2012; 9 (2): 568–75.
29. Elhilali MM et al. Prospective, randomized, double-blind, vehicle controlled, multicenter phase IIb clinical trial of the pore forming protein PRX302 for targeted treatment of symptomatic benign prostatic hyperplasia. J Urol. 2013; 189 (4): 1421– 6.

Source: Herberts M et al. The Effect of LUTS / BPH and Treatments on Ejaculatory Function. Curr Urol Rep. 2016 Jul; 17 (7): 48.

90,000 Premature ejaculation treatment

By Mika Miro (Medow) 4 min read Views 46 Published by

Treatment of premature ejaculation requires an understanding of the processes that occur during orgasm and ejaculation, and learning how to delay them. Male orgasm has two distinct phases: the first is the sensation of orgasm, and the second is ejaculation, although these two phases usually coincide. Orgasm without ejaculation is possible: a man may experience “retrograde ejaculation” when semen is poured inside (usually into the bladder), or “dry orgasm” due to the side effects of certain medications, or frequent orgasms without ejaculating ( this is when a man is capable of multiple orgasms, but not all men are endowed with such joy).Men can also cum without orgasm (a condition known as dripping).

During the reaction to sexual stimulation, the orgasm phase is characterized by two subphases: a feeling of ejaculatory inevitability and the release of semen. Immediately before ejaculation, its inevitability is felt, that is, the feeling “I’m about to finish,” which comes when the seminal fluid reaches the base of the penis, one to three seconds before the ejection of the semen. This is the feeling that is so well known: if you are going to cum, nothing will stop you.

In order to master control over your ejaculation, you should familiarize yourself with the response of your body to sexual stimulation, that is, know at what point your body reaches the state of ejaculatory inevitability, and learn how to restrain ejaculation just before that moment. Men, who do not lose control over the onset of semen ejection, know how to reach the platophase in their sexual arousal, from it to the moment of ejaculatory inevitability, but they still cannot restrain an orgasm.In mastering control over this process, a useful tool is the development of the pubococcygeal muscle, which is responsible for curbing ejaculation and masturbation as a means of studying your body and its response to arousal.

Masturbation as a means of controlling one’s arousal

Masturbation until the moment of ejaculatory inevitability and focusing on the physical sensations experienced during this will allow you to explore your sensations, which must be monitored during intercourse in order to control this process.You can also learn to continue intercourse longer using a method known as “push the alarm”: masturbate to the alarm and do not allow yourself to cum before it rings. Gradually set the signal for longer and longer periods of time, and you will develop the ability to have long sex. In reality, this method only allows you to study the physical sensations during the plateau phase and sensations immediately before ejaculation, and not to treat premature ejaculation.

Masturbation as a therapy for premature ejaculation is effective when using the stop-start method (or the squeeze method. A man who intends to treat premature ejaculation needs not only to learn how long to continue intercourse, but also to understand that long-term sex is better Long-term sex with a long foreplay and subsequent intercourse promotes increased blood flow to the genitals, an increase in the sensitivity of all nerve endings and, as a result, the achievement of a stronger, brighter orgasm.The longer you have sex, the stronger your enjoyment will be.

Medicines

This treatment is not always recommended, but antidepressants (Priligy – a drug against premature ejaculation) are available on the market, which slow down the blood flow to the penis and reduce the need to ejaculate. Doctors try not to prescribe pills to treat premature ejaculation, but in cases where non-drug treatments do not help, drug therapy can sometimes be successful.For men who have depression as the cause of premature ejaculation, medications can also help solve the problem. In addition, studies have shown that if a man who is not depressed takes antidepressants such as Zoloft, he usually has no side effects. If you believe that drug therapy may be better for you than technical methods, seek the advice of a sexologist and therapist.

Special exercises

There are Kegel exercises that help men develop the muscles of the pelvic girdle – muscles that respond to sexual stimulation and contract during orgasm.Training the muscles of the pelvic girdle solves two problems: it, firstly, allows you to develop these muscles so that when a man needs control or a pause, he has the opportunity and knows how to do it, and secondly, it helps a man learn to feel his body and his response to sexual arousal. The stronger the muscles of the pelvic girdle, the stronger the orgasm will be and the more reliably the man will be able to control the duration of intercourse and the onset of orgasm.

TANIZ-K 0.0004 N30 CAPS PROLONG RELEASE

Classification of the incidence of side effects recommended by the World Health Organization (WHO): very often> 1/10; often from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; rarely> 1/10000 to <1/1000; very rarely from <1/10000, including individual messages; the frequency is unknown (cannot be estimated from the available data).

Often

Infrequently

Rarely

Very rare Frequency unknown

Nervous system disorders Dizziness (1.3%) Headache

9363 – – Visual disorders – – – – Blurred vision *

Visual impairment *

Cardiac disorders – Feeling of palpitations – – –

Vascular disorders – Orthostatic hypotension – – –

Disorders from the respiratory system, chest and mediastinal organs – Rhinitis – – Nasal bleeding *

Disorders from the gastrointestinal tract – Constipation, diarrhea, nausea, vomiting – – Dryness of the oral mucosa *

Skin and subcutaneous tissue disorders – Skin rash, pruritus, urticaria Angioneurotic edema Stevens-Johnson syndrome Multiform exudative erythema *, exfoliative dermatitis *

Genital and breast disorders Ejaculation disorders (including retrograde ejaculation, ejaculatory insufficiency) – 907

General disorders and disorders at the injection site – Asthenia – – –

* data obtained in the post-registration period

Cases of intraoperative instability of the iris of the eye (narrow pupil syndrome) during surgery for cataracts and glaucoma in patients taking tamsulosin.