About all

What causes a dry vigina: The request could not be satisfied


Vaginal Dryness: Causes and Moisturizing Treatments

Normally, the walls of the vagina stay lubricated with a thin layer of clear fluid. The hormone estrogen helps maintain that fluid and keeps the lining of your vagina healthy, thick, and elastic.

A drop in estrogen levels reduces the amount of moisture available. It can happen at any age from a number of different causes.

It may seem like a minor irritation. But the lack of vaginal moisture can have a huge impact on your sex life. Fortunately, several treatments are available to relieve vaginal dryness.


Vaginal dryness is common symptom of menopause — and close to one out of every three women deals with it while going through “the change.” It becomes even more common afterward. It also makes the vagina thinner and less elastic. This is called vaginal atrophy.

Estrogen levels can also drop because of:


Other causes of vaginal dryness include:

No matter what the cause, vaginal dryness can be extremely uncomfortable. It can lead to itching, burning, and painful intercourse.


Any burning, itching, or discomfort in the area is worth a call to your doctor or gynecologist. They’ll ask about your past health and find out how long you’ve had symptoms and what seems to make them worse or better.

Your doctor will do a pelvic exam, checking your vagina for any thinning or redness. The exam will help rule out other possible causes for your discomfort, including a vaginal or urinary tract infection. The doctor may also remove cells from your vaginal wall or cervix for a Pap test.


The most common treatment for vaginal dryness due to low estrogen levels is topical estrogen therapy. These replace some of the hormone your body is no longer making. That helps relieve vaginal symptoms, but it doesn’t put as much estrogen in your bloodstream as the hormone therapy you take in pills.


Most women use one of three types of vaginal estrogen:

  • Ring (Estring): You or your doctor inserts this soft, flexible ring into your vagina where it releases a steady stream of estrogen directly to the tissues. The ring is replaced every 3 months.
  • Tablet (Vagifem): You use a disposable applicator to put a tablet into your vagina once a day for the first two weeks of treatment. Then you do it twice a week until you no longer need it.
  • Cream (Estrace, Premarin): You use an applicator to get the cream into your vagina. You’ll typically apply the cream daily for 1 to 2 weeks, then cut back to one to three times a week as directed by your doctor.

Any estrogen product can have side effects, such as vaginal bleeding and breast pain. Topical estrogen may not be recommended when you:

  • Have breast cancer, especially if you’re taking an aromatase inhibitor
  • Have a history of endometrial cancer
  • Have vaginal bleeding but don’t know why
  • Are pregnant or breastfeeding

There isn’t much research on the long-term use of topical estrogen, but doctors believe it’s safe.

Other Products

You can buy a vaginal moisturizer like glycerin-min oil-polycarbophil (Replens) at your local drugstore or supermarket.

A drug taken orally An oral drug taken once a day, ospemifeme (Osphena), makes vaginal tissue thicker and less fragile, resulting in less pain for women during sex. The FDA warns that Osphena can thicken the endometrium (the lining of the uterus) and raise the risk of stroke and blood clots.

Take your time before having sex to make sure that you’re fully relaxed and aroused. Apply a water-based lubricant (Astroglide, K-Y) to help enjoy intercourse more.

Avoid using douches, bubble baths, scented soaps, and lotions around the sensitive vaginal area. These products can worsen dryness.

Estrace Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

See also Warning section.

Stomach upset, nausea/vomiting, bloating, breast tenderness, headache, or weight changes may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Tell your doctor promptly if you see the tablet in your stool.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), increased or new vaginal irritation/itching/odor/discharge, severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, increased thirst/urination.

This medication may rarely cause serious problems from blood clots (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism). Get medical help right away if you have any serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of the body, confusion, trouble speaking, sudden vision changes (such as partial/complete blindness), pain/redness/swelling of legs, tingling/weakness/numbness in the arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.

A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Ospemifene Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

See also Warning section.

Hot flashes, vaginal discharge, muscle spasms, and sweating may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may rarely cause blood clots (such as pulmonary embolism, stroke, heart attack, deep vein thrombosis). You may be at increased risk for blood clots if you are severely dehydrated, or have a history of blood clots, heart/blood vessel disease, heart failure, stroke, or if you are immobile (such as on very long plane flights or being bedridden). Before using this medication, if you have any of these conditions report them to your doctor or pharmacist. Get medical help right away if any of these side effects occur: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, weakness on one side of the body, sudden vision changes.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Vaginal dryness Causes – Mayo Clinic

Reduced estrogen levels are the main cause of vaginal dryness. Estrogen is a hormone that helps keep vaginal tissue healthy by maintaining normal vaginal lubrication, tissue elasticity and acidity. Other causes of vaginal dryness include certain medical conditions or hygiene practices.

Estrogen levels can fall for a number of reasons:

  1. Breast-feeding
  2. Childbirth
  3. Cigarette smoking
  4. Effects on your ovaries from cancer therapy
  5. Immune disorders
  6. Menopause
  7. Perimenopause (the transition time before menopause)
  8. Oophorectomy (ovary removal surgery)
  9. Use of anti-estrogen medication

Other causes of vaginal dryness include:

  1. Douching
  2. Sjogren’s syndrome
  3. Use of allergy and cold medications

Causes shown here are commonly associated with this symptom. Work with your doctor or other health care professional for an accurate diagnosis.

  • Definition
  • When to see a doctor

Dec. 04, 2020

Show references

  1. Bachmann G, et al. Clinical manifestations and diagnosis of genitourinary syndrome of menopause (vulvovaginal atrophy). https://www.uptodate.com/contents/search. Accessed Nov. 5, 2020.
  2. AskMayoExpert. Genitourinary syndrome of menopause (adult). Mayo Clinic; 2019.
  3. Hoffman BL, et al. Benign disorders of the lower reproductive tract. In: Williams Gynecology. 4th ed. McGraw Hill; 2020. https://accessmedicine.mhmedical.com. Accessed Nov. 5, 2020.
  4. Ferri FF. Sjogren syndrome. In: Ferri’s Clinical Advisor 2021. Elsevier; 2021. https://www.clinicalkey.com. Accessed Nov. 5, 2020.
  5. Peterson ZD. Treating sexual problems in aging adults. In: The Wiley Handbook of Sex Therapy. John Wiley & Sons; 2017.
  6. Kingsberg SA, et al. Female sexual health: Barriers to optimal outcomes and a roadmap for improved patient-clinician communications. Journal of Women’s Health. 2019; doi:10.1089/jwh.2018.7352.

Products and Services

  1. Book: Mayo Clinic The Menopause Solution


Why is my vagina dry? Vaginal dryness causes, diagnosis and treatment

This article is also available in: português, español

Top things to know about vaginal dryness:

  • Vaginal dryness can have physical or psychological causes

  • Vaginal lubrication is often closely tied to levels of the hormone estrogen, which changes at various life stages

  • Medications (including hormonal birth control) may cause vaginal dryness

  • You can have a happy and healthy sex life even if you don’t produce much natural vaginal lubrication

Vaginal dryness is common but treatable, and can happen at any age. Symptoms may include a burning sensation, vaginal discomfort or itching, abnormal vaginal discharge, or pain during sex or masturbation.

There can be a number of reasons for vaginal dryness, both psychological and physiological. Whether you’re drier than you would like to be during sexual activity, or are experiencing more general discomfort due to vaginal dryness, here are some of the possible causes—and solutions:

Why is my vagina dry? Common causes of vaginal dryness

Vaginal dryness and estrogen levels

The hormone estrogen helps to keep the vagina moist and to maintain the thickness of the vaginal lining. Atrophic vaginitis (vulvovaginal atrophy) is a common condition that can occur when the ovaries produce a decreased amount of estrogen, which includes the prominent symptom of vaginal dryness (1).

Your body produces less estrogen:

  • At the time of menopause—then it is classified as genitourinary syndrome of menopause

  • After having a baby, particularly if breastfeeding

  • Medications which interfere with reproductive hormone regulation, such as those which treat breast cancer or certain gonadotrophin releasing hormone agonists.

  • Removal of the ovaries, chemotherapy, or radiation therapy of the pelvis (1-5)

Vaginal lubrication and sex

If you’re noticing dryness during vaginal sex, this could be for a number of reasons. Maybe what your partner is doing just doesn’t turn you on. If you feel turned on but are still dry, your body might simply need time to catch up with your brain. If you’re noticing vaginal dryness along with a lack of sexual desire, you may be experiencing low libido, which can be caused by a number of factors including medication and health conditions. Or you just might not be all that into your partner or the acts you are performing together.

Your sexual desire is influenced by some of the same hormones that fluctuate with your cycle, like estrogen and progesterone.

You may find your desire tends to increase in the days leading up to ovulation and decrease after ovulation is over (6,7). Sex drive may be lower when more progesterone is produced during the luteal phase (the days after ovulation and leading up to menstruation) (7). Exactly how reproductive hormones influence desire and preference isn’t the same for everyone; some people report a higher sex drive as part of their premenstrual experience, while other present with decreased libido (8). Tracking desire throughout your cycle can help you discover what’s true for you.

Download Clue to track your sex drive and sexual activity.


over 2M+ ratings

Vaginal dryness treatments

If you’re experiencing dryness since being on medication or a form of hormonal birth control: talk to your healthcare provider about trying another one that’s a better fit for your body.

If you suspect your dryness could be caused by low estrogen levels, there are several treatment options: vaginal moisturizers or lubricants, local vaginal estrogen cream or tablet,  systemic estrogen (and progesterone) therapy, or sometimes selective estrogen receptor modulators (SERMs) (3). See your healthcare provider to find out what’s the best option for you.

If what your sexual partner is doing doesn’t work for you: you could try discussing your sexual likes and dislikes—you may even find that just talking about it increases your arousal. If you lack desire for your partner, it’s up to you what you do from there, whether you want to re-evaluate your relationship or investigate any health issues that might be messing with your libido.

If you feel turned on but you’re not wet: spending more time on foreplay can be one way to increase your natural lubrication. Another option is to use personal lubricant (lube) during sexual activity or masturbation.

Use a personal lubricant for “simply better sex”

In a 2013 study, lubricant use was associated with higher ratings of sexual pleasure and satisfaction in both solo masturbation and partnered sexual activities. More than 9 out of 10 women in the study agreed or strongly agreed that lube made sex feel “more comfortable,” “more pleasurable,” and simply “better” (9).

Lubricants made with water or silicone can be used with latex condoms and diaphragms. Oil-based products, such as petroleum jelly, baby oil, mineral oil, or vegetable oils are not healthy to use internally, and are likely to damage latex condoms and/or diaphragms and make them less effective at preventing pregnancy or STIs.

A study published in the journal Obstetrics and Gynecology found that women who had used petroleum jelly as lube in the past month were more than twice as likely as non-users to have bacterial vaginosis (10). Hand or body lotions are not recommended either, as they can be irritating to vaginal tissues.

If you prefer to use something natural, avoid using food products like olive oil or coconut oil as this can lead to yeast infections or bacterial vaginosis. Instead, try an organic lubricant or a water-based lube without additives.

Other possible causes of vaginal dryness

Aside from sexual arousal and estrogen levels, there are additional factors that can affect vaginal lubrication:

Vaginal dryness can be a side effect of some medications and contraceptives. Talk to your healthcare provider to find out if the source of your vaginal dryness could actually be your medication or contraception (11).  

Cigarette smokers have been shown to have an increased risk of an earlier menopause transition as compared to non-smokers. This means that atrophic vaginitis symptoms may appear at a younger age in this population (2).

Sjögren’s syndrome could be another cause of possible vaginal (and other symptoms of dryness). This is an autoimmune disease where the body’s glands aren’t able to produce enough moisture (12).

If you’ve checked out everything else and still don’t find the culprit, you might have an allergy to chemicals in soap, detergent, lubricant or hygiene products—these can also cause vaginal dryness or irritation. Try switching to natural products and wash with unperfumed soap or just water, and see if your symptoms improve.

Your vagina is self-cleaning, so there is no need to use any internal washes (douches) or vaginal deodorants—in fact, they can be harmful. Research has linked the practice of douching with increased risk of bacterial and yeast infections, pelvic inflammatory disease, cervical cancer, increased transmission of STIs, upper genital tract infections, endometritis (inflammation of the lining of the uterus), and other adverse health outcomes (13,14).

Use Clue to track vaginal fluid throughout your cycle.

Article was originally published on Oct. 13, 2017.

How to pick a lubricant

This article is also available in: português, español

Personal lubricant (lube) can be used to help make sexual acts—like sex, masturbation, or sex toy play—more pleasurable. Lubes work to reduce friction between your skin and the person/object/or body part that you are using, which can eliminate chafing, pain, and uncomfortable rubbing.

Why use lube?

Why not use lube? Lube is great! Using lube is nothing to feel shameful about—it can be a great addition to your sexual experience. You should not feel embarrassed to use a personal lubricant. Many people who produce ample amounts of vaginal fluids still choose to use a lube to further increase their sexual pleasure.

Around half of post-menopausal women tend to notice more vaginal dryness and discomfort when having sex (1,2). After menopause, the genitourinary area (including the vagina and vulva) may change and atrophy due to the decrease in estrogen levels. Without higher levels of estrogen, these tissues become thinner, less flexible, receive less blood flow, and produces less natural vaginal fluids (1). Using a lubricant helps decrease the discomfort of sex when experiencing vaginal dryness, but does not prevent the underlying problem of vaginal tissue atrophy.

Some people may experience vaginal dryness, which can lead to discomfort or pain during intercourse. Every person is different. People who are breastfeeding, who are taking medications (including antihistamines and antidepressants), breast cancer survivors, and people with Sjogren’s syndrome may also often experience vaginal dryness (2). In these situations, a lubricant can be helpful.

Download Clue to monitor your cervical fluid


over 2M+ ratings

Lubricants produced by your body

There are many fluids that your body produces that can act as lubrication, many of which depend on where you are in your cycle:

Menstrual blood can be used as a lubricant for masturbation or sex at the beginning of your cycle.

Cervical fluid, particularly around the time of ovulation, will provide you with a slipperier glide (just remember that having unprotected heterosexual sex around the time of ovulation has the greatest chance of pregnancy).

Vaginal and arousal fluid is available to you all month to help moisten and lubricate your vagina. Be sure to make enough time for foreplay to allow your arousal pathway to produce enough fluids.

Saliva can also be used as a lubricant. Using your own saliva to masturbate may actually be protective against the development of vulvovaginal candida (3). Researchers think this could be due to some of the protective bacteria and antifungal properties found in saliva, plus a lack of immune response against your own fluids. In comparison, receiving cunnilingus (oral sex on the vulva) may actually increase your chances of getting a candida infection (3).

How to pick a lube

Water-based lube is your safest bet to start with. It can be used for all of your sexual needs: penetrative sex, masturbation, and sex toy play. Water-based lubes are also ideal for people with sensitive skin or vaginal irritation, and can be used with condoms and sex toys (4). They are also really easy to clean out of sheets and clothes, and won’t leave a stain.

Water-based lubes do have some downsides though. They are not good for water-play/shower sex, as they will just wash away. Also, water-based lubes tend to get sticky and require frequent re-application. So if you are planning to have marathon sex, might we suggest another type of lubrication?

Silicone-based lube is slippery, long lasting, and is ideal for a longer session (4). It requires less lube be applied, and needs reapplication less often. Silicone-based lubes are also great for shower sex or masturbation in the shower, as they don’t wash away so easily. The catch is that silicone-based lubes are a bit more tedious to wash off, as you will need soap and water to clean up afterward. Sometimes silicone-based lubes may also stain sheets.
(Word of caution: never spill a bottle of silicone-based lube on your hardwood floors—it will stain and leave your floor slightly slippery for months.)

Silicone-based lubricants should not be used with silicone-based sex toys, as they can break down the rubber over time. However, this doesn’t mean all sex toys are off limits with silicone-based lubricants—there are many toys made from other materials, like hard plastic, glass, and steel.

Oil-based lube also provides a slippery feel that lasts longer than water-based lube. These lubes are ideal for masturbation (hands or toys), penetrative unprotected sex, and water-play. Oil-based lubes can also be used for a sensual massage.

Oil-based lubes (or any other oil products like petroleum jelly or mineral oil) should not be used with latex condoms, as they can dissolve the latex of the condom and may cause latex condoms to break (4). Latex diaphragms and latex sex toys should also be also kept away from oil based lubricants. Non-latex condoms (like those made of polyisoprene) are also sensitive to oil-based personal lubricants, so check the package before use (5).

Another downside to oil-based lubes is that they can be more difficult to clean off of sheets and your body.

Lubes for anal sex

Personal lubrication is recommended for anal sex since the anal canal does not produce fluids to help ease penetration. Plus, the tight muscular sphincter at the entrance of the anus offers much more resistance than the vagina, which is full of folds and stretchable tissue.

Using a personal lubricant can also make anal sex safer. Using a water-based lubricant decreases the chances of condom breakage while having anal sex, in contrast to oil-based lubricants or saliva, which both increase the chances of condom breakage during sex (6). The chances of the condom slipping off during anal sex are also related to lubrication. Applying lubrication to the outside of the condom can decrease chances of slippage, while applying lubrication to the inside of the condom can increase chances of slippage (6).

Good to know before you buy

In general, avoid any lubricant that contains any artificial flavors, colors, sugars, essential oils, additional additives, or glycerine—you never know how you’ll react to these additives. Especially if it’s your first time using a personal lubricant—some of those extra features like “warming” or “tingling” can be more overwhelming than expected. Also, just because a product is “natural” doesn’t necessarily mean it’s better for you. Check the ingredients list, read product reviews, or go to a sex toy shop and ask the experts there.

Glycerin or glycerol is a sugar alcohol that is sometimes used in lubricants. The verdict is still out on whether there is a link between glycerin/glycerol containing lubricants and the health of the bacteria in your vagina. Some evidence suggests that lubricants containing glycerin may increase the chances of vaginal infections, while others actually find glycerin makes no difference to the microflora of the vagina at all (7,8). More research is needed here.

Sometimes a large amount of glycerols (and other similar compounds) are used in lubricants to provide special properties, like warming sensations or extra slipperiness (5). A lube with a high concentration of glycerols can actually have a negative effect on anal and vaginal tissues, by causing damage and dehydration to these tissues (9-11). This tissue damage is not only uncomfortable, but can also increase the risk of STI transmission (5).

When picking a water-based lube, try to pick one that reflects the acidity of a healthy vagina—around pH 3.8 to 4.5—to prevent increased risk of bacterial vaginosis (5). The anus has a more neutral acidity level (pH 5.5 to 7), so also try to pick a lube appropriately here too (5).

Some lubricants may also contain spermicide chemicals, but these may cause irritation to the vagina, and are therefore not recommended for use (5). If you are trying to conceive and are using lube, make sure to buy one that is specific for conception, as some lubricants may decrease sperm motility.

Painful sex—a caution

If sex is painful to you, increasing lubrication isn’t always the answer. Many illnesses or infections can present with symptoms of pain during sexual intercourse, particularly vaginal sex. This includes skin disorders, inflammation, infections, hormonal changes, trauma, and many other causes (4). If you do experience recurrent or worsening pain during sex, see your healthcare provider.

Download Clue to track your period, cervical fluid, and sex.

Learn about

your body and women’s health

Hi, I am Steph! I’ll send you both educational and entertaining stories about women’s health and share tips and tricks to get the most out of your Clue app!

Menopause and Perimenopause: The Basics

This article is also available in: português, español

Top things to know

  • Menopause is when menstrual cycles end. The average age at menopause is 51 in Western countries, though ethnicity, behavior, and environment may influence menopause timing.

  • Perimenopause is the transition into menopause. Menstrual changes start, on average, 4 years prior to menopause, though that’s not the case for everyone.

  • Lifestyle modifications, medications, and supplements may help with uncomfortable menopause changes.

What is menopause? 

Menopause is when someone’s menstrual cycles come to an end, and pregnancy is no longer possible. The word menopause is from the Greek root word men, meaning “month” and pausis meaning pause or cessation.

Menopause is a unique experience—humans are 1 of only 4 species on the planet who experience it (1). For some people, it’s both an ending and a beginning. It can bring a lot of new changes, and for some people it might not feel like much of a change at all.

Menopause is a normal life phase, but can also be induced by surgery, drug treatments, or medication. It technically begins after your last menstrual period, but your healthcare provider will consider you to have reached menopause after 12 months without a period (2).

What is perimenopause?

Perimenopause is the body’s transition into menopause (peri comes from the Greek word for “around”). You may not have heard the term before, because people often confuse perimenopause (the transition period) with menopause (the time after your last period).  

Perimenopause can be as short as a few months or last up to 8 years. On average, it lasts around 4–5 years (3-6). During perimenopause, hormone levels fluctuate and then decline, giving rise to new sensations, symptoms, and changes. Experiences of perimenopause vary widely across people and cultures.

Why it’s important to know about menopause and perimenopause

Every woman and person with a cycle who goes through the natural aging process will experience these life stages. Despite this, they are still underrepresented in culture and research.

Knowing what changes are possible can help you identify the transition in yourself. Also, because it’s still possible to have or develop reproductive conditions like polycystic ovary syndrome (PCOS) or endometriosis during perimenopause, it’s important to know what the probable signs of perimenopause are, and what symptoms might be signs of something else.

Learn about

your body and women’s health

Hi, I am Steph! I’ll send you both educational and entertaining stories about women’s health and share tips and tricks to get the most out of your Clue app!

When does perimenopause start? What is the average age of menopause?

The exact start of perimenopause—the transition into menopause—is hard to pinpoint. One study that tracked women as they transitioned into menopause found that menstrual irregularity began on average between ages 47 and 48. But it can begin much earlier or later. In that same study, of those who were still menstruating at age 45, about 1 in 3 reported menstrual irregularity. At age 52, about 1 in 10 reported that they were still menstruating normally (3). There are other perimenopausal changes and symptoms that may be felt before menstrual irregularity begins, which may help in identifying a different starting point of perimenopause, but more research is needed.

Menopause—when periods actually stop— happens on average at age 51, but most people reach it anywhere between ages 45–55 (3,5,7,8). About 4 in 10 women reach menopause by age 50, 9 in 10 will reach it by age 55 (3).  

Menopause is considered “early” when before age 45, and  “premature” when it happens before age 40. Premature menopause is also sometimes called primary ovarian insufficiency (POI) or premature ovarian failure (not the greatest of terms). About 1 in 100 people experience premature menopause for non-surgical or chemotherapy-related reasons (8-10). 

Download Clue to track the regularity of your period.


over 2M+ ratings

Early menopause can be caused or influenced by cigarette smoking, certain medications,  chemotherapy, and possibly insulin resistance and type 2 diabetes (10,11). 

People who have an oophorectomy (removal of the ovaries) will undergo menopause immediately. Sometimes people who have had a hysterectomy (removal of the uterus) will also experience early menopause, even if their ovaries are not removed (9,11). People who have had menopause induced due to surgery, drug treatments, or medication generally do not experience perimenopause, since there is an abrupt stop to their reproductive function. But people with induced menopause may still experience symptoms of menopause.

How long does menopause last? (How long does perimenopause last?)

You might ask: how long does menopause last? Perimenopause is the transition period, and menopause is the time after your last period. 

The menstrual cycle irregularities of perimenopause last an average of about 4 years, from the beginning of menstrual irregularity to the last period. But it can last anywhere from a few months to ~8 years (3-6). About 1 in 10 people may experience the transition more abruptly, with only a few months of menstrual irregularity. These people also tend to report fewer symptoms like hot flashes (3).

What can affect the age of menopause?

Smoking: yes.

Hormonal birth control: maybe. 

Your genetics, environment, and lifestyle may all play a role in how you experience perimenopause, and the timing of perimenopause and menopause. People who reach menopause later in life tend to have shorter transitions (10). Smokers tend to be slightly younger at perimenopause and have shorter transitions, reaching menopause about a year earlier than average. There are likely other differences due to ethnic background and/or related environmental and behavioral factors, but more research is needed on this topic (12).

A person’s pregnancy history and their history of oral contraceptives (OCs) use might delay menopause. Studies on the topic are mixed—some studies have found an association, and others not—and the biological reason why this would be the case (if true) is not fully understood (5,10,13). Although being pregnant and using OCs suppresses ovulation, they don’t suppress the development (and death) of eggs prior to the point of ovulation, so why using OCs would impact timing of menopause is still unclear.

Menopause symptoms & signs: Physical and emotional changes of perimenopause

Perimenopause is whole-body change. It influences everything in your body that involves estrogen and progesterone, along with other hormones and proteins. Some of these changes and symptoms go away after menopause is reached, and others are longer lasting. Some advocates argue that these changes can be felt well before changes show up in the menstrual cycle, but there is little research on this so far.

The changes during perimenopause and after menopause are caused by the decline in the number of eggs in the ovaries. The menstrual cycle is driven, in part, by the development of eggs. This process impacts our levels of estrogen and progesterone, among other hormones. Once the number of eggs in the ovaries decreases beyond the point when reproductive hormone levels can be maintained, changes start to occur.

It can be difficult to know when ovulation will happen during perimenopause, so use reliable contraception if you are having penis-vagina sex. Getting pregnant becomes more difficult during this time, but it’s still possible.

To get an idea of when you’ve entered perimenopause, track changes to your menstrual cycle, and be aware of other common symptoms and changes you might be experiencing. 

Common changes and symptoms in perimenopause include:

  • Hot flashes (aka hot flushes) 

  • Sweating 

  • Disturbed sleep 

  • Changes in mood and anxiety 

  • Migraines 

  • Increased forgetfulness 

  • Changes in sexual desire 

  • Vaginal dryness and itchiness

  • Lowered fertility/infertility

  • Increased abdominal body fat (14-19). 

Lasting physical changes to be aware of include loss of bone density, vaginal dryness, changes in urination function, and changes in sexual function (14,20,21). 

Fortunately, the end of menstrual cycles also means the end of any negative symptoms you may have experienced during your cycle, like cramps, as well as the risk of unintended pregnancy.

How the menstrual cycle changes before and during perimenopause

1. At first, you may notice that your period arrives slightly earlier each cycle (ie shorter menstrual cycles) and is heavier.

As you approach perimenopause, your hormone levels begin to change. This happens before your periods become unpredictable. For some people, one of the earliest signs of perimenopause is that their periods arrive slightly earlier—meaning that their menstrual cycle shortens, by ~2–4 days This is due to a shortening of the follicular phase (the first part of the menstrual cycle), as ovulation happens more quickly (19,22-25).

Download Clue to track your cycle length and changes.


over 2M+ ratings

(Note: Cycles can also become shorter for other reasons, so don’t assume you’re entering early menopause if your cycle becomes slightly shorter in your 30s. Average cycle length decreases with age, from about 29 days for people in their 20s, to 26 days for those in their 40s (26,27). Cycles can also become shorter due to a shortening of the luteal phase, caused by any factor leading to a decrease in the ovary’s production of progesterone after ovulation (28).)   

During perimenopause, less estrogen is produced. But before perimenopause, estrogen levels can actually rise for a while, and progesterone levels typically decrease (19,29). This is what shortens the follicular phase, and may also cause other changes, symptoms, or sensations. You may notice changes to the heaviness of your period during this time. Lower progesterone—with or without higher estrogen—may also lead to heavier periods, which is more common in early perimenopause (19).

2. Later, you may have irregular cycles and bleeding changes. 

As the number of follicles in your ovaries decreases, ovulation becomes less common, and hormone levels start to fluctuate more and more. Menstrual cycles might become longer, and then progressively more variable—longer and shorter, with menstrual periods that are heavier, lighter, and far less predictable (19,23,30,31). 

The heaviness of your period will also fluctuate. Cycles without ovulation may have lighter periods, while periods that come after a long cycle may be long (32). On average, about 6 of the final 10 cycles before menopause are prolonged and anovulatory (where ovulation doesn’t occur) (33). In the 1-2 years before menopause, it’s common for cycles to last more than 5 weeks (31,33). 

3. No period, period.

As ovulation becomes rare, your period might go away for months at a time, and then return (6). This phase lasts between 1-3 years for most people, but again, everyone is different (6). Eventually, menopause is reached, and cycles comes to an end, along with the period.

About 1 in 10 people may stop menstruating more abruptly, with much less prolonged irregularity (3).

Menopause treatments: How can I manage symptoms of menopause and perimenopause? 

You might have searched for “menopause treatment.” Quick reminder: perimenopause is the transition period before menopause. It is a normal function of the body, but some of the changes it causes can feel uncomfortable, or even rageful. 

If you are experiencing symptoms that affect your quality of life, such as hot flashes, vaginal dryness, changes in mood, or difficulty sleeping, seeing a healthcare provider or a perimenopause specialist can be a good idea. 

Lifestyle changes for menopause symptoms 

There are some simple changes you can make in your lifestyle to help you cope with menopausal symptoms. 

Some dietary adjustments may be helpful, (see below and in the supplementation section), but there is no known “menopause diet” to provide guaranteed menopausal symptom relief. Much more research is needed to understand what lifestyle changes may be useful treatments for menopausal symptoms. 

Some first steps that may be helpful:

Prepare for hot flashes

Dressing in layers and having cool water and beverages available to you may help with managing hot flashes (21). 

Drink in moderation 

Drinking less than 1 drink per day probably doesn’t decrease rates of hot flashes, but the effects of drinking higher amounts of alcohol are unclear, and may worsen symptoms—you’ll have to see what’s true for you (34).


Exercise has been found to be beneficial for overall wellbeing during and after perimenopause. Studies have also found that exercise, particularly aerobic exercise might reduce hot flashes, though the effect is small if it exists (35). A recent study that looked specifically at resistance training (i.e. lifting weights) also decreased the frequency of hot flashes (36). 

Stop smoking 

Smoking has been linked to increased hot flashes and night sweats (34).

Maintain a healthy weight 

This may help to protect against hot flashes and night sweats, since people with heavier body masses tend towards having more frequent symptoms (34). 

Invest in personal lubricant and vaginal moisturizer 

These will be helpful for relieving symptoms of vaginal dryness and pain during sex (37,38).

Hormone replacement therapy (HRT) for menopause symptoms

Hormone replacement therapy (HRT), also called hormone therapy, is sometimes prescribed during or after the menopausal transition to help relieve certain symptoms, like hot flashes, night sweats, and vaginal dryness. HRT involves taking synthetic or “bioidentical” forms of estrogen and often synthetic progesterone. “Systemic” HRT goes throughout the whole body and can be taken in several forms, like pill, patch, gels, creams, and sprays. For people who are only experiencing vaginal symptoms, “local” HT used inside the vagina in the form of a cream, ring, or tablet may be recommended (21,39). 

Also, data suggest that systemic HRT lowers the risk of osteoporosis, coronary heart disease (CHD) and overall mortality in people who take it around menopause, particularly for those who have had a hysterectomy and use estrogen-only HRT, but more information is needed (39. 

Systemic HRT also carries risks, including an increased chance of developing breast cancer, stroke, and blood clots (39-41). Risks vary by whether your form of HRT contains a progestin or not (39). Also, the risk of negative effects increases when people begin taking it after menopause, particularly 10 or more years from menopausal onset (39,40). The U.S. Federal Drug Administration (FDA) currently recommends that people who choose HRT take it “at the lowest dose that helps and for the shortest time” (41). 

(We have a whole article on HRT and different risks here.)

During perimenopause, some healthcare providers may also suggest using hormonal contraceptives to help manage abnormal bleeding and some other symptoms. Hormonal contraceptives can also help prevent unintended pregnancies, which are still possible during perimenopause.

Non-hormonal medications for menopause symptoms

Certain medications that are primarily used to treat depression, high blood pressure, and seizures—SSRIs, SSNRIs, clonodine, and gabapentin—have been found to also be effective in reducing hot flashes, although they may be less effective than HRT (21). 

There is also a type of medication called selective estrogen receptor modulators (SERMs) which are non-hormonal, but have effects similar to estrogen on certain parts of the body. One SERM, Ospemifene, is approved to treat painful sex caused by vaginal dryness (21,42). 

Similarly, a combination medication containing estrogen and a SERM, called Duavee, is used to treat hot flashes and prevent osteoporosis (weakened bones due to low density) (43). 

These medications can have unwanted side effects, so it’s important to have a discussion with your healthcare provider about benefits and risks.

Alternative and “natural” treatments and supplements for menopause symptoms 

There is no scientific consensus on the benefits or risks of any complementary or alternative treatment for menopausal symptoms. Many small trials may show individual benefits, but when data from multiple studies is analysed together the results are difficult to draw conclusions from (44). This important area of research is greatly underfunded, leaving people to test things on their own, or take other routes. 

Some examples of treatments that have been explored: 

Acupuncture for perimenopause and menopause

Acupuncture treatments seems to provide little to no effect on menopausal symptoms, though for some people it may be better than no treatment at all. 

Body mindfulness for perimenopause and menopause

Body mindfulness therapies like relaxation and breathing techniques may be helpful at providing some relief for hot flashes and are not harmful to try. 

Supplements for perimenopause and menopause

Plant and dietary supplements have mixed and unclear results, including Black cohosh (Actaea racemosa/Cimicifuga racemosa) a popular herb often prescribed for menopausal symptoms is not effective at relieving hot flashes. Phytoestrogens such as those found in soy may provide some benefit to relieving hot flashes and vaginal dryness, but no do help with night sweats (44-50). We’ll be writing more on current “natural” approaches to perimenopause symptom treatment. 

Using dietary supplements can also have negative side effects, and some supplements may interact with other medications, so speak with your healthcare provider before treating your perimenopausal symptoms with supplements. 

When should I see a healthcare provider?

During perimenopause and menopause, talk to your healthcare provider if:

  • You are concerned about the heaviness or length of your period

  • You begin to bleed between periods, especially if you have a history of polycystic ovary syndrome (PCOS), are higher weight, have a family history of uterine cancer, or have taken estrogen-only hormone therapy or certain medications to prevent breast cancer .  

  • You experience any spotting or bleeding after reaching full menopause

  • You experience bleeding during penetrative sex (2,51,52)

Abnormal bleeding during perimenopause

Although changes in bleeding are to be expected during perimenopause, some bleeding changes may be caused by abnormal changes to your endometrium (i.e. the lining of your uterus). If the endometrium becomes too thick and irregular, it can develop into cancer, but this can usually be prevented if caught early (2). 

Abnormal bleeding after menopause

In some cases, bleeding continues after menopause. It is easy to mistake this type of bleeding for symptoms of perimenopause, which may mislead someone to think they have not reached full-menopause when they actually have. 

Any spotting or bleeding after menopause is abnormal and should be checked out by a healthcare provider (2). Spotting or bleeding after menopause can be caused by a medical condition, such as uterine polyps (2). Uterine polyps are growths on the inside lining of the uterus (the endometrium), and become more common with age (53).

She – reviews and reviews – KinoPoisk

To the description of the film ”
by rating
by date
by username


90,036 11-20 of 29


There is no more melancholy story in the world…

I watched this boring, in all respects, film to the end, only because I hoped for some kind of revelation that the author was eager to share. But with each passing minute, this hope became more and more illusory.

For 126 minutes I was forced to observe the life of an absolute pessimist, incapable of experiencing any feelings other than impenetrable green melancholy.

At first, I tried to explain this melancholy by the departure of my wife, or loneliness, but no matter what happened in the hero’s life, the melancholy did not recede from him for a minute.

Theodore just goes with the flow, making no attempts to somehow change this very life. His wife left and he seems to be painfully going through this breakup, but he does not try to return her. With new acquaintances, he also does not succeed, because he does not put any effort into making it something more.He doesn’t need it.

It is not at all clear what the film is about.

When it comes to the value of human relations, the main character, and the film world as a whole, do not appreciate them. Otherwise, people themselves would write tender letters to each other.

If the soul is the most important thing in a relationship, then the film lacks sincere emotional impulses.

If it is about the relationship between artificial intelligence and humans, then it seemed to me that AI is too human, and the main character, like a robot vacuum cleaner, is boring and predictable so much that even the operating system could not stand it and abandoned him.

The most amazing thing about the film is that the colors in it are quite bright, but the impression remains as if you were looking at the gray dregs for two hours.

The bottom line is not comforting at all. The film is boring, and contains neither intellectual nor emotional components. I do not recommend it for viewing.

direct link

November 22, 2014 | 11:30

The key episode of this film, in my opinion, appears in the middle of the film, when Amy Adams and Joaquin Phoenix play the ideal mom and dad on the computer, smiling happily, collecting the bonuses of ideal parents.We are talking about the basic instinct, which each of them suppress. Each of them loves the pleasant cocoon in which they are both involved. Nice, but at the same time the heroine of the moment – Amy Adams is chewing on some dry snacks. This completely optional ‘seizing’ fixes the deep frustration that she is experiencing while living not her life at all, but some kind of incubation of it.

Well, the film itself gives us a verbose fantasy about a man’s romance with his operating system.As it quickly turns out, no one likes our protagonist, and the virtual conversation turns out to be much closer to him than the unknown, which can hide a dangerous monster named vagina dentata. Against the background of his not too clever relationships with women, we get an inspired stream of merging with an immaterial substance of the opposite sex. As in the most boring Woody Allen films, we find ourselves witnessing deep conversations and a non-stop stream of consciousness about the two characters’ own experiences.Deprived of a bit of irony and filled with sublime illusionist motives, the cybernetic tale turns into an ordinary chatter. Figuratively speaking, in the choice between a copy and a fake, our hero is limited to a photograph of the reflection of a fake. His inspired idyll was likely to spark deep conversations about sex substitutions on the Internet or human loneliness. But, as for me, this is the only way to talk about boredom. All the characters proposed by Spike Jones are incredibly boring. Bored is Spike himself and his script.

Dry snacks. Loneliness on the net. A romantic loser played by Joaquin Phoenix. Surrogate intimate contact involving an operating system. Everything is so close and almost hits the very target, but in the proposed shell it turns out to be nothing more than a sample of bad taste. Like many (but fortunately not all) masters oriented towards an intellectual American audience, Spike is incredibly clever, appeals to profundity and soulfulness, while trying to match the trends. However, behind the beautiful signboard, in fact, there is ordinary chatter.

4 of 10

direct link

August 30, 2014 | 05:33

I set myself up to watch an intelligent film (I won’t even write ‘smart’ – now they practically don’t shoot such films) – of course, I didn’t see anything good there.A film with good actors and a very unfinished script I give 5 out of 10. I do not advise you to waste time on it.

Now I ran my eyes over the reviews written before me – a lot of people are worried about the question – how exactly the main character made love to the computer. The fact that Joaquin Phoenix is ​​having phone sex with some abnormal aunt 25 minutes earlier is no surprise. The answer is simple – in both cases, self-satisfaction.

In general, the whole film is about self-satisfaction.About how easily you are ready to believe any words of any mechanism, if only everything was about you, beloved, and for you, beloved. Loneliness, vanity and pride will do anything – a man will marry a coffee maker, but I would like this ‘main idea’ of the film to be presented gracefully and, sorry, deeper. Otherwise, in fact, it turns out that there is nothing to dive into – Joaquin plays very mediocre – endlessly, with the same feigned gesture, he adjusts his glasses on his nose and smiles botanically. In the middle of the film, during their ‘honeymoon’, the situation with the plot became so bad that, best of all, the phrase ‘the screenwriter went on vacation’ reflects it – for the abundance of indistinct burdensome piece scenes ‘about nothing’ read off scale.By the end of the film, the scriptwriter, having rested, came out of vacation, and the film could be watched, but without any pleasure.

In general, it is interesting to observe the psychology of deep and multifaceted people, and when in the center of events there is a person for whom a great achievement in life, that he came to the beach with a phone – to sit without undressing – to play with the keys is somehow boring. I love movies about teenagers, but what does Joaquin Phoenix have to do with it?

direct link

July 08, 2014 | 00:53


She: disappointed expectations

Perhaps, indeed, what is shown in the film is a part of our life, but this is not a reason to show it all.In this way, you can get to the point of showing the acts of defecation and urination. I think there are some facets of what we take for granted, and in this film, the authors overdid it with the themes of sex, lust and desire for carnal pleasures. In Lost in Translation, for example, the emotions, desires and aspirations of the protagonists are shown with great taste and tenderness.

In general, the film ‘She’ can be compared to the film ‘Lost in Translation’. Both there and here the theme of loneliness is present, both films often begin to resemble a parable, the authors of which invite us to walk through the expanses of the loneliness of the protagonist.Further differences begin. If in Sofia Coppola’s film it touches, then here I personally did not find much that would hurt me, and in those moments when some kind of contact with the film was about to begin, crude vulgar dialogues sharply destroyed the established connection. Perhaps the world has already degraded to the level of seeing some kind of romance in such crude vulgarity, but then I had not yet had time to degrade along with the world. The joke about the anus under the arm and anal sex is the most revealing example of this overkill.By the way, in my opinion, the joke of the heroine Scarlett Johansson about anal sex is also discordant with her velvety and soft voice. Still, her voice is more attuned to kissing and something more romantic than anal sex in the armpit. I hope I managed to convey the idea here.

Regarding the main idea of ​​the film that all computers are controlled by voice. Probably, this is promising, but it is implemented in the film too primitive and it is clear that it is completely inconvenient for the user.In fact, the control over the entire time of the film is carried out only by reading mail. Again, perhaps people are already so degraded that they can only view mail on a computer, but this is not the case. You can do something else on the computer. And the mechanisms of voice control in some other issues are not shown in the film. I think this is a flaw in the film. I understand that the command ‘print’ was sounded there, several computer games with voice and hand control “through the air” were also demonstrated, and speech input of information was also shown, but, again, the proportion of reading mail was undeservedly large.This moment annoyed me a little.

Due to this imbalance of the film between emotions, technology and vulgarity, the episodes I mentioned at the beginning of the review, showing the loneliness of the protagonist and his experiences, were no longer perceived.

In general, the very idea of ​​love with a computer looked weak from the very beginning, albeit original (well, maybe not entirely original).

It is worth paying attention to the poorly worked out moments of the script in terms of the relationship between the computer and the user.The operating system is a person. This is already strange and raises many questions. For example, what it is like to be an operating system – a person, and how it should feel. Also, one of the serious blunders is to admit that the whole plot revolves around the fact that the computer operating system is SHE. But at the beginning, the user is offered a choice: choose a male or female voice. And if the user chose a male voice, would their relationship develop as well? What would change in this case? Also, the topic of sex with a computer causes some bewilderment.Where did the main character go when he made love to the operating system? Where does the computer program get the sensation of this penetration? It is entirely, if it were in reality, an illusion or a pretense. It’s good that at least the heroes of the film admit to themselves that their relationship sometimes resembles pretense.

Some scenes in the film are reminiscent of the Hayao Miyadzaki anime. In this he resembles ‘Lost in Translation’ and this is already a plus for the film. Although, of course, if you watch a film for the sake of such lyrics, then there is not enough of it.

The ending of the film is probably a little better than the beginning, but nothing more.

In general, in my opinion, the film is a one-off, which, in general, you don’t need to watch. Nothing in this film touched me, except for the performance of Ema Adams. But she also swears a lot in this film.

In general, after some films there is such a feeling of unrealized pretentiousness, which for some reason is annoying. After this film, there is such a feeling. I also watched Spider-Man: High Tension, which also left a feeling of wasted time and being a little tricked.Perhaps this is about disappointed expectations.

6 of 10

direct link

06 July 2014 | 19:52


The past is a story that we tell ourselves.

So, the near future – what is it?

In his work, Spike Jones wanted to clearly show how modern gadgets can make life easier for a person. Theodore is a lonely writer, buying a new technical development – an operating system designed to fulfill any user’s desire. To Theodore’s surprise, a romance soon arises between him and the operating system.

The only thing that begs for a positive assessment is the idea that allows the director to put IT technologies on the level of real human relationships. By this, he clearly shows that human dependence on gadgets can soon turn into this kind of absurdity, which will nullify real relationships between real people. Is it an absolute evil that will eventually force a person to become asocial? Undoubtedly.

But the director does not answer the main questions facing the viewer.Is there any future for this kind of relationship? If it’s worth getting involved in, why and why not? The main character is a real plankton who no longer sees anything good in this life. He is connected only by a divorce from his wife, after which he, apparently, cannot recover and only does that he suffers and cries into a vest for a non-existent mechanism with a female voice, which, by the way, will then begin to upset him with his illogical actions and periodic hysterics …

As for the end, it is greased. This film clearly does not pull on the very masterpiece that is worth thinking up on your own.

The director’s idea is clear enough, but too many sentimentally constructed shots in the film are simply off the charts. The main character is a rag on which everyone who could wipe his feet.

5 of 10

direct link

June 21, 2014 | 17:05


Virtual Love

I am quite a loyal person, but this film seemed to me just stupid.And I don’t understand the excitement around him.

Because this is nonsense, not love! The protagonist seriously tells his friends that he is meeting with a computer, and they nod in understanding.

In real life, they would twist him at his temple and say that he is a wanker-loser.

For example, what would you say to a 14-year-old boy who is obsessed with computer games and says that he is not interested in real life? You wouldn’t say that playing computer games masterly is as wonderful as playing Mozart on the piano, right? Since computer games do not give a person anything except that he kills his time.They do not form him, he does not create anything. So is this ‘love’.

I remember 15 years ago, when the Internet was just emerging, I got it one of the first in my class. I was in the 10th grade then. So, all night long I hung out in chats for communication with strangers from other cities. It was so new and exciting! Then there were no VKontakte, no dating sites. And we communicated without seeing each other’s photos, without knowing the age and name. Cognized each other from the inside, without an outer shell! It was mysterious and exciting, and here I can understand the main character.Although I communicated with real people, and not with computer intelligence. And gradually, attachment, increased interest and feelings arose for someone. We called each other virtual boyfriend and girlfriend. When I told my friends about this, they, of course, listened, but, naturally, they considered it all frivolous. There were stories with an interesting ending that virtual couples eventually met in real life, and occasionally even later got married. But most of these acquaintances did not develop beyond virtual communication. And this is logical.This gets boring over time, I want vivid sensations and vivid emotions, the development of events, and not endless correspondence at night. And there are so many lively interesting people nearby, with an attractive appearance, their own individuality, who show you signs of attention.

And in this film, everyone seems to be obsessed with loneliness, living in solitary cells. One and all were captured by the epidemic of computer love. And no one cares that events do not develop. The director is simply not in the know, it seems, how it actually happens.

3 of 10

direct link

May 02, 2014 | 13:33

The author’s idea is quite understandable – fear of virtual technologies, loneliness of people, etc.d … These fears, it seems to me, are absolutely exaggerated. At the dawn of telephony, many people were afraid of this, then new, device. Like ‘what a horror, now every man can call a woman when she is at home!’. Wait, it’s just ridiculous, huh?

Therefore, the film was somehow ridiculous. Technically, he’s downright delusional. Starting from the fact that if artificial intelligence were really invented, it would certainly have been initially used for clearly different purposes than being sold for a penny by a common man in the street.About this intelligence itself with a female voice and, probably, ‘female logic’, I will not say anything. As well as about his emotions, (surprise!) Orgasms and other nonsense. Little things, you tell? I don’t know, but all this frankly interfered with my viewing.

And I do not believe that, clearly not a complete crazy, the main character, ‘fall in love’ with this device. For if he is a simple madman, then the film should not arouse any interest, for it does not carry any idea. But Theodore, initially, is not like that. On the phrase, when he proudly said, ‘my girlfriend is an OS’, and the couple in the office, understanding, nodded their heads, I just slapped my hand in the face… The word ‘meet’ (in the generally accepted sense) means sex, which is difficult in the case of the hero’s love for the computer. There are probably a lot of people now having pen pals from across the world, but they’re just ‘pen pals’. Navryatli, at least in some society the wording ‘I am meeting’ will be applicable to this case. And in the film, as we can see, yes! Why is that??? Well, yes, people are strange some, ‘alienated’ due to the vastness of technology, but damn it, not complete freaks! One of the basic human instincts (sexual, of course!) Cannot be canceled by any technology.For a man to fall in love and become attached to a woman, he must see that this is a woman. And desirably attractive to him. This is our nature. In this film, very little was shown of real relationships between people. Why did such degradation become possible? And is it even possible? Some senseless torment of the protagonist, and incomprehensible loyalty to the device …

As a story of ‘pure love’, the film is also bad. Love is not only when they listen to you, when you cry into your vest. And not only when they make you laugh.This is self-sacrifice, overcoming conflicts, full-fledged communication, etc. … I did not see all this in the film. Only empty chatter.

The episode with the dead cat was funny and interesting. Obviously more like the relationship and sex of the future than the snot of the protagonist.

Another plus: good acting, especially Phoenix. The music is beautiful and the picture is good. But even that doesn’t save the movie

3 of 10

direct link

April 30, 2014 | 02:50

After watching it, I got the impression that the director filmed the psychiatrist’s observations of a schizophrenic.In psychiatry, multiple personality disorder is classified as one of the manifestations of schizophrenia and this film is quite suitable as a visualization for a dissertation in psychiatry.

You are interested in the thoughts and deeds of a calm schizophrenic – then you, inappropriately, should watch this film.

The second personality of the protagonist, played by Joaquin Phoenix, is a certain Samantha. According to the plot, it is positioned as an advanced operating system from the future, but in terms of actions it is a typical second person, hence the sexual fantasies, sometimes perverted – like an anus in the armpit.The Phoenix hero delights into schizophrenia like a drug addict in a narcotic trance.

There is no history here, so boredom starts to prevail after half an hour of viewing. Joaquin Phoenix is ​​not an actor who can keep the viewer for two hours, 80% of the screen time is occupied by his dialogues with his second personality, although, most likely, this is due to a weak script and direction.

Pleased with two jokes: the first – when asked by Phoenix whether he is the only one with Samantha, she replies that no, he is the 613th; and the second – Samantha will be him in the middle of the night and saying: ‘I love you, good night.’is turned off.

Perhaps Spike Jones wanted to shoot something like ‘Simone’ or a philosophical parable about replacing human communication with communication with artificial intelligence, but in the end we got the most boring notes of a psychiatrist.

3 of 10

direct link

April 12, 2014 | 22:23


Cyber ​​Pervert Love Story

I’ll start, probably, with the positive aspects that were still in this film.

I will not arrange a boring retelling with a psychological analysis of the actions of the heroes of the film, because I am not a psychologist and I have no desire to try to look like such a glamorous philosopher, which many here are trying to portray. I offer a dry analysis of the film from a man for whom science fiction is one of his favorite genres. So, the positives:

1. Not a bad idea for a movie. The idea itself is certainly not new, but in general it is not yet muddy and, if properly executed, has good potential.It is a pity this case is not one of those.

2. Aesthetically, the film was shot beautifully. There is nothing to complain about here.

3. The actors did not bother either, they played their roles well.

4. Excellent musical accompaniment. Here, too, you can put the top ten for the performance.

Well, from the positive, that’s essentially all. Moving on to the fun part.

1. I went to the movie with my wife and our eleven-year-old daughter asked to go with us. I’ll say right away that it’s just wonderful that she didn’t go, because in the cinema the film was positioned as a fantastic melodrama with an age limit of 12+.I even have a ticket somewhere else. I understand that this claim has nothing to do with the filmmakers, but the feeling that we almost came with my daughter was rather unpleasant.

2. This item flows out smoothly from the first. Of course, I understand why the scene of virtual sex with a dead cat was introduced at the beginning of the film, but to be honest, the first impression of the film was already spoiled.

3. The interest in what is happening after the next scene of virtual sex of Theodore with his virtual system which has no body, but which at the same time very emotionally and voluptuously managed to get an orgasm, was completely lost.It is very interesting to ask the director where she did it, because orgasm is a physical pleasure, and at the time of their first sex, she was only very sorry about the fact that she had no body. After this scene, until the end of the film, I did not leave the feeling that the developers of this OS with artificial intelligence are simply the most vicious trolls, who initially programmed their system to harshly mock their weak-willed users.

4. Actually the next point is the meaning of the film.It is clear that the director put a rather deep meaning into his creation, and not just one, but several at once. Basically, the film seems to be thought-provoking, but the confusion is confusing. There is no feeling of disclosure of the topic.

5. I don’t even know how to start. I’d rather not even do this, but just say – do not try to make films with a fantastic bias if you are a layman in it-technologies. Alas, it looks very funny and ridiculous. What annoyed the film most of all was its positioning as fantastic.And this film is not the first one that stumbles upon this rake.

4 of 10

direct link

March 10, 2014 | 11:23


You and I have a future, but it’s so fuzzy

The beginning of the film attracts interest with its seemingly original idea: the future, one representative of office plankton Theodore, writing touching letters for people to their relatives and friends, experiencing with them their holidays, memorable dates and anniversaries, being himself a boring and self-contained person with a crumbling personal life, finds an original “helper” – a new OS.We must pay tribute to the main character of the film, played by Joaquin Phoenix, he brilliantly conveys the emotions and mood of his character.

However, despite the talent of Phoenix and the innovation of Spike Jones regarding the plot of the film, the further the “relationship” of Theodore and his new passion goes, the funnier and more ridiculous they look. The hypertrophied signs of an introvert and a notorious pessimist, manifested in a lonely writer, reach their climax in having sex with the very same OS Samantha.It is completely incomprehensible what Theodore expects from his romance with her, is this romantic with a fine mental organization so naive that, fleeing the inner pain caused by the recent divorce, he can plunge headlong into the virtual world of his new iron girl, and rejoice like a child all this, not noticing the strangeness of their behavior?

Further, the character and mood of the film, which is mainly projected by the mood of the protagonist, more and more resembles a sinusoid: everything is fine in one scene, an emotional outburst and upsurge, it seems that such irrational love is possible and no matter what happens next, but exactly in the next episode Broken hearts, a fallen spirit and suffering from the realization of the inability to be together peck.Such fluctuations occur several times, and the film towards the end seems drawn out and tedious, as if these features were transferred to the picture from Theodore himself.

The ending is still boring and predictable: a harsh reality that once again reminded of the importance of relationships between people and the danger of falling into the tenacious clutches of virtual networks. I give one point for the cast, one more for the idea of ​​the film, and two more get good music in the film and the director’s attempt to show the complex relationships between people, as a result of which others escape into another reality.

4 of 10

direct link

03 March 2014 | 17:09


90,036 11-20 of 29

Bartholin gland cyst | Private clinic “Medic” Cheboksary

Definition of the disease.Causes of the disease

Bartholin’s gland cyst is a benign round cavity (saccular formation with thin walls and the presence of a secret of different consistency inside) formation in the lower third of the vaginal vestibule as a result of a violation of the outflow of secretion from the cavity and its accumulation in it. The cyst cavity stretched with a secret can have various sizes, reaching 7-9 cm in diameter.

Cysts of the Bartholin gland are observed mainly at the age of up to 30 years (hormonally active reproductive age) and account for 2% of all diseases of the female genital organs with actively functioning and hormonally dependent Bartholin glands.

Before we move on to the mechanism of development of this pathology, we will consider the normal anatomy and physiology of the Bartholin glands.

Bartholin glands or large vestibular glands are located on both sides of the vestibule vestibule, in its lower third in the thickness of the labia majora. They are a paired organ. They got their name in honor of the Danish anatomist Kaspar Bartholin Jr. who discovered them. Their size is about 1.5-2 cm, the excretory duct of the Bartholin gland, 1.5-2.5 cm long, opens on the inner surface of the labia minora at the border of its middle and posterior third.In some cases, their atypical location occurs, for example, in the thickness of the labia minora [13]

The function of the Bartholin glands – moisturizing the mucous membrane of the vulva during arousal during sexual intercourse, which prevents dryness and soreness during intercourse. Due to the presence of mucin in the composition of the secret, it has a bactericidal effect.

The main causes of this disease are frequent inflammatory processes in the genital area caused by specific and nonspecific microflora, such as staphylococci, streptococci, Escherichia coli, and the causative agents of sexually transmitted infections – gonococcus, chlamydia, etc.Increasingly, microorganisms are isolated that cause diseases of the upper respiratory tract – streptococci pneumonia and influenza sticks [2]

Tears of the soft tissues of the perineum during childbirth and trauma, surgical manipulations on the external genital organs (episiotomy – incision of the soft tissues of the genital fissure in childbirth to prevent their rupture in an unfavorable place, followed by the imposition of raffia sutures, chiurgical perineoplasty – surgical plastic surgery of the soft tissues of the perineum, surgical labioplasty – surgical plastic of the labia in the form of reducing their size).

More often in crops of the secretion of cysts of the Bartholin gland – the growth of diagnostically significant flora was not found. The causative agents for inflammation of the Bartholin gland cyst and the transition to an abscess (above we were talking about the microflora leading to the causes of inflammation leading to the appearance of the cyst) can be and representatives of the normal microflora of the female genital organs, such as staphylococci, streptococci, Escherichia coli, and causative agents of sexually transmitted infections – gonococci, chlamydia, etc.Increasingly, microorganisms are isolated that cause diseases of the upper respiratory tract – streptococci pneumonia and influenza sticks [2]

Often cysts may be preceded by acute bartholinitis inflammation of the Bartholin gland without blockage of the duct (cysts in this case develop both after treatment after a while, and during the absence thereof.


Bartholin gland cysts are common problems in women of reproductive age.Most often, women complain about aesthetic moments – the asymmetry of the labia, swelling on one side of the labia majora. Cysts are usually asymptomatic and can be detected by a gynecologist during a routine examination. But in some cases (hypothermia, acute or subacute inflammatory process of the respiratory tract, acute or subacute inflammatory diseases of the genital tract, pelvic organs), they can increase and cause significant pain. Women with larger cysts may experience discomfort when walking, sitting and having sex.If the Bartholin gland functions on the other hand, the vaginal moisture during intercourse does not change. From the side of blockage and the presence of a cyst, the Bartholin gland cannot fully function. [2] . [1]


The resulting inflammation of the surrounding tissues occurs in 3 stages:

1 stage Alteration – damage to cells and tissues both by microbes themselves and by enzymes produced during the destruction of cells, which change the structure and disrupt the normal metabolism of the connective tissue and blood vessels surrounding the focus of inflammation, resulting in the process 2 stages Exudation there is a release of fluid and blood cells from the vessels into the tissue, edema occurs.

3 stages – Proliferation (or productive stage) does not occur, since damaging factors continue to act and therefore the resulting edema, thickening of the walls, narrowing of the lumen of the canal, thickening of the secretion, resulting in a blockage of the duct), The secretion of the Bartholin gland produced, accumulating , thickening, leads to the formation of a cystic cavity formation, gradually increasing in size. Local defenses cannot cope due to concomitant diseases, a decrease in general immunity and the aggressiveness of the flora causing inflammation.Reaching a size of 4 or more centimeters, squeezing the surrounding tissues, it causes pain in a woman and can, turning into an inflammatory process, cause an abscess of the Bartholin gland [2] [3] [4]

The causes and mechanism of development of the Bartholin gland abscess are described below, in the Complication section.


By ICD code – 10 – N75.0 Bartholin gland cyst

By localization, cysts can be:
– unilateral;
– double-sided [1] [2]

This disease no longer has any other classification options, even unofficial ones.


1) Chronic bartholinitis – chronic, more than 3 months, inflammation of the gland of the vestibule.

In this case, the formation in the area of ​​the labia majora, accompanied by soreness on palpation of the affected gland, redness, tissue edema, can be both a complication and a primary cause of the cyst of the Bartholin gland. Treatment is aimed at destroying the causative agent of the disease and relieving symptoms of intoxication.

2) Bartholin gland abscess [1]

Under unfavorable conditions (secondary infection (migration of bacteria from nearby areas (genital tract, cervical canal, uterine cavity, urinary system or separated foci – oropharynx, respiratory tract), weakening of immunity), cyst suppuration occurs with the development of an abscess of the Bartholin gland.

There is a body temperature, intoxication, a sharp deterioration in health. Locally, there is an increase in the size of the formation from 10 to 12 cm, a feeling of bursting and a sharp pulsating pain in the perineal region. Any movement can make the pain worse.

On palpation – fluctuation, increased skin temperature.

An abscess of the Bartholin gland can open spontaneously with the release of pus. Since abscess formation of the Bartholin gland cyst is often associated with genital infections, there may be clinical symptoms of colpitis, urethritis, endocervicitis, the main symptoms of which are edema and hyperemia of the mucous membrane, itching, leucorrhoea

Method of treatment – planned or emergency hospitalization, during which – an autopsy is performed with subsequent drainage of the abscess, anti-inflammatory (broad-spectrum antibiotics), detoxification therapy.

3) Cyst recurrence occurs quite often in situations such as self-opening, surgical opening or puncturing of the cyst.

1. Rectovaginal fistula as a complication of excision of the Bartholin gland. This is a pathological canal between the rectum and the vagina as a result of ongoing inflammation and fusion of the surrounding tissue.

Rectovaginal fistula may occur after removal of the Bartholin gland. Case [12] illustrates a rare and serious complication of a commonly performed gynecological procedure

Complaints in patients can be – pain in the perineum, pain during intercourse, bowel movement.To establish and confirm the diagnosis, after taking anamnesis, carrying out a gynecological and rectovaginal examination, additional examinations, consulting a proctologist. The tissue defect is eliminated using an autograft, a biological collagen plug, and a titanium clip. If a fistula is detected during pregnancy, natural childbirth is prohibited. With adequate treatment, the prognosis is good.

2. Sepsis – a systemic inflammatory reaction in response to a local inflammatory process in the area of ​​the Bartholin gland cyst.The response to the release of toxins formed during the destruction of harmful microorganisms in the absence of appropriate therapy is accompanied by a failure syndrome on the part of many organs and systems, which can lead to death.


The diagnosis of a cyst of the Bartholin gland (including with an asymptomatic course) is more often made on the basis of an objective examination: asymmetry of the genital gap, an increase in the volume of one or less often of two labia majora. If the cyst of the Bartholin gland is not inflamed, the skin over it retains its normal color.On palpation, the gynecologist determines in the thickness of the labia majora a slightly painful cystic formation of an elastic consistency.

Laboratory tests: nonspecific [3] (in blood and urine tests, if the cyst is uncomplicated by inflammation, there will be no changes

Instrumental studies: ultrasound of the external genital area is determined anechoic or hypoechoic avascular (non-reflecting or poorly reflecting ultrasound, on the screen we see a rounded formation with thin – light walls and absolutely dark or with a light suspension of contents) formation with thin walls

List of main diagnostic measures at the outpatient stage:

1.General blood analysis;

2. General analysis of urine;

These blood and urine tests are taken within the framework of the standard, to prepare for surgical treatment and to exclude concomitant pathology from other organs with their subsequent correction)

3. Smear for microflora and degree of purity.

This is an examination method in which the test material is taken from the surface of the mucous membrane of the vagina, cervical canal and urethra. The purpose of the analysis is to assess the composition of microflora and identify inflammatory diseases.The assessment of the standing of the natural flora has four degrees of vaginal cleanliness in its classification:

1 degree – in the smear epithelial cells and a normal number of lactobacilli, pH – acidic;

2 degree – a small number of leukocytes, fewer lactobacilli, gram-positive diplococci are present. pH – remains acidic;

3 degree – increased number of epithelial cells and leukocytes, decreased lactobacilli, many coccal bacteria, pH – slightly acidic or alkaline;

4 degree – a large number of epithelium and leukocytes, pyogenic microorganisms, the absence of lactobacilli, pH – alkaline.

4. Bacterioscopic examination of the vaginal discharge and the contents of the cyst – allows you to identify the microbial agents that caused the cyst of the Bartholin gland: identification of the pathogen, sensitivity to antibiotics.

5. Examination for infections (ELISA, PCR) gonorrhea, trichomoniasis, chlamydia. [3]

Required volume of examinations before hospitalization:

1. Blood for antibodies to pale treponema (this is the detection of total antibodies class M and G to the causative agent of syphilis) – a necessary analysis before hospitalization and surgery !!

2.Blood group and Rh factor.

3. Complete blood count.

4. General urine analysis.

5. Smear for the degree of purity.

6. Bacterial culture from the cervical canal.

7. HbsAg – surface antigen of the hepatitis B virus – to detect hepatitis B by its presence and establish its concentration, the necessary analysis before hospitalization and surgery !!

8. Anti HCV.

In women during menopause or perimenopause, excisional biopsy is indicated to exclude adenocarcinoma, since at this age the risk of developing malignant tumors is greatest

Differential diagnosis

Includes cystic and solid lesions of the vulva such as epidermal inclusion cyst, hidradenoma papilliferum and lipoma [3], vulvar neoplasms; – Bartholin gland abscess; – bartholinitis; abscess of the vulva.

Hematoma in the vulva – while there may also be complaints of education in the vulva, discomfort during sexual intercourse, pain. But when taking anamnesis; and a gynecological examination – a woman associates its appearance with mechanical trauma, childbirth; And the location is not in the projection area of ​​the large gland of the vestibule. [1]

Paraurethral cysts – similar complaints. On examination – swelling in the paraurethral region (the area near the urethra) [1]

Furunculosis of the labia majora. Complaints about formations in the perineal region, general malaise, hyperemia, edema, hyperthermia. On examination, the formation is localized in the area of ​​the hair follicle, the sebaceous gland. [1]


Small, asymptomatic cysts can be left untreated except for cosmetic reasons.

It is often tempting for the clinician to simply cut open the cyst or abscess because this technique can be effective for other common abscesses. However, a simple piercing of a cyst or abscess of the Bartholin gland can lead to a relapse, since the edges of the tissues close again very quickly during puncture or incision due to the rapid healing or regeneration process. [6]

Only large cysts, usually 3 or more centimeters, are subject to surgical treatment, which interfere with daily activity and sexual activity, disrupt the aesthetic appearance of the external genital organs of a woman.

The main task of surgical treatment is organ-preserving – the formation of a canal and restoration of the function of the Bartholin gland ,

Types of surgical treatment

Inserting a catheter – Word

This is a modern method of surgical treatment for Bartholin gland cyst, especially in case of its recurrence.

Under local anesthesia, the cystic area is opened with a small incision of about 5 mm, the contents are removed and sent for bacteriological examination, the cyst cavity is washed and a Word catheter is installed in it (this is a 55 mm long silicone tube, 5 mm in diameter with a channel inside, blindly ending, with more thin walls at the end, due to which the tip can inflate into a ball, which has no analogues), inflating its rubber tip to 3 ml with saline solution of 0.9% sodium chloride, thereby fixing it in the cyst cavity.For better fixation and prevention of prolapse during the movements of a woman, it is recommended to apply 2-3 absorbable interrupted sutures along the contour of the catheter emerging from the cyst cavity. The other end of the catheter is inserted into the vagina. The catheter remains in the cyst cavity for 6 weeks. This is aimed at forming a channel for the passage of secretions, the walls of which do not grow together. Research shows that the Word catheter is an easy-to-use, inexpensive outpatient procedure with acceptable short-term relapses.Treatment costs are seven times lower than with marsupialization [7]. While the catheter is in the cyst cavity, the patient is recommended to be in sexual rest in order to avoid its prolapse. In a number of countries, there is no such limitation, since studies have shown that the pain symptom caused both by the cyst itself and by the procedure performed with the catheter in the cavity over time (by the 6th day) completely disappears [8]

As an alternative, a catheter Voroda or Jacobi ring is used (the catheter has no channel, more solid, ring-shaped) which is inserted through 2 punctures in the mucous membrane and the cyst capsule and the 2 ends are fastened to each other.

Nina Brockmann and Ellen Dahl

psychological gender can
be different from genetic or
physical, inherited by the person
at birth.

The gender issue is wrong
simple as it seems. We hope that
information provided
will interest you and allow you more
look at the world and its

Discharge, menstruation and other

Vagina (as well as other holes in
human body) serves as an outlet,
and not just a place where something
shove. Come out of it
screaming babies, blood, mucus and
other troubles.It brings
incredible joy, sometimes
causes anxiety and also gives
the ability to understand what is down there,
not everything is fine. All of this too
are controlled by hormones. So it came
time to talk about biological
fluids associated with female
intimate area.

Syringe and
“Disco mouse”

Allocations. Listen to this
word. It evokes associations with
tsunami and brown rivers
which flow in impassable
forests and teeming with crocodiles. But for
you and me allocation is
transparent, milky or
yellowish spots that
constantly stain your underwear
after puberty.It is not surprising, therefore, that
discharge is not what we love about
speak loudly and often. They are
perceived as something nasty
and dirty. And at the same time the thought of
wet female genitals
causes great

So what is it
discharge? Is there any difference between them
kinds? And why are we so concerned
by them?

Discharge is a liquid
escaping from the vagina
moment like on our genitals
the hormone estrogen begins to influence.
Part of the discharge is formed in
glands located in the neck
uterus.The vagina does not have its own
glands but fluid seeps out
through its walls and mixes with
moisture from the cervix
and from the glands at the entrance to
vagina, including from
bartholin glands.

discharge is small – usually from
half to one teaspoon per
day, although their number
differs from woman to woman, and
also depends on the phase of the cycle. Many
of those who use
hormonal contraceptives, and
pregnant women notice that discharge
become more intense.The consistency of the discharge too
varies from transparent
liquid to thick mucus that looks like
for protein, on the eve of ovulation.

The discharge is not just natural –
they are required because
promote self-cleaning
vagina. The task of selections is
keep the vagina clean and
drive uninvited guests out of it,
such as fungi and bacteria, and
at the same time remove dead cells
mucous membrane. Besides, in
secretions contain many
beneficial lactic acid bacteria,
the so-called lactobacilli.They are
produce, you guessed it,
lactic acid. It gives
discharge slightly sour
smack and smell.

More importantly,
what lactic acid provides
normal acid-base
balance that is perfect
it is necessary that everything in the vagina
was ok. Most
the main harmful microbes,
causing diseases
dislikes acidic environments. Besides
addition, lactic acid bacteria
prevent the growth of disease-causing
bacteria, because they are fighting for one and
the same habitat. As a result
the infection does not develop.So
way, allocations support
genital health.

They simultaneously lubricate and
moisturize the mucous membrane.
Dry mucous membranes can easily
crack, and then the problems are not
keep you waiting. Imagine
just what the mouth would be without

The problem is
what causes discharge in many
disgust: they count
a sign of untidiness or bad
taking care of body hygiene. Rare
the girl will leave dirty linen on
mind in the bathroom. And some come
so far as to strive by itself
rinse the vagina clean from
discharge.You have never
thought about associations,
syringe related? Nina too
didn’t think until I moved
in the USA, where I bought a product for
intimate hygiene in the store and
put it in a common soul. Soon
giggling fellow student advised
her to remove this remedy, because
there are already rumors about the Norwegian
girl with a syringe.

“Syringe?” – surprised
Nina. And a fellow student told her that
everyone decided that she was washing
vagina with perfumed soap –
evidently common practice among
female sex workers.Nina tried to explain what it was
simple detergent
intimate zone – with a pH of 3.5 and all that, but
soon gave up and stopped
attempts to convince a fellow student.
Good girls are by no means
should draw attention to the fact
that the intimate area sometimes needs
in the shower. Even the very admission is
that you wash your intimate area,
belonged to the category of taboo, as
as if it could reveal a great
secrets about secretions. Nina left
bottle in the shower.

Why women
strive to cleanse the vagina? For
most of the reason lies in
smell.Many of our interlocutors
were worried
Do they smell “normal”. They are
worried that a colleague
sitting next to the meeting could
smell their intimate
zones, and did not allow sexual
partners to do cunnilingus,
afraid that the smell is capable
push the man away.

In healthy
the genitals have a smell. Such is
a life. Fresh discharge has
slight sour smell and taste
thanks to lactic acid bacteria.
At the same time, the groin and
the vulva is abundantly supplied with sweat
glands.Tight trousers
synthetic underwear and
crossed legs – from it all
it gets warm between your legs and
well. And during the day you
naturally sweat. Combination
discharge accumulated for a whole
day, sweat and urine residue
will certainly give a smell. Between

The value of immunomodulatory therapy (use of vaginal suppositories) in treatment of HPV-associated neoplasia | Kononova

Comparative analysis of the results of the adjuvant therapy in 60 patients with HPV-associated cervical neoplasms.It is established that the use of local immunomodulatory therapy with Polyoxidonium before conducting destructive methods of treatment improves the state of local immunity, promotes the normalization of microflora of the vagina and elimination of human papillomavirus, increases the effectiveness of therapy, reduces the recurrence of the process.

Currently, there is an increase in precancerous diseases and cervical cancer (CC) among women of reproductive age, while the incidence of cervical cancer is increasing by 2.1% every year [1-4].Cervical cancer ranks first among all oncogynecological diseases in women under the age of 30 (27.9%). This indicates a high frequency of infection of women with human papillomavirus (HPV) at a relatively early age, when the cervical epithelium is especially susceptible to infection [5-7]. Cofactors in the development of diseases are disorders of the cellular and humoral immunity of the epithelium, since HPVs have tropism for epithelial tissues [8], while the E7 oncoprotein expressed by highly oncogenic HPV types causes immunosuppression at the local level during the transition of the virus to the stage of integrative infection and creates favorable conditions for the reproduction of opportunistic and pathogenic microflora, the addition of the inflammatory component [9-11].In the intermediate layer of the stratified squamous epithelium of the cervix, HPV can persist for a long time even after destructive treatment, which contributes to the recurrence of the process in 35% of cases, the occurrence of complications in 22-38% of cases [12, 13]. The growth of diseases associated with papillomavirus infection (PVI) and the high oncogenic role of infection with the formation of cervical cancer, immunosuppression caused by the virus and a large number of complications after destruction determine the need to develop a complex therapy, which includes, along with destructive – application of immunocorrection by new methods of treatment.Since immune dysfunctions develop at the local level [14], in order to correct it, it is advisable to carry out local therapy. For the study, we selected a high-polymer immunomodulator Polyoxidonium (affecting all links of immunity, depending on its state in a particular patient) in order to carry out immunocorrection at the stage of preparation for destruction. The aim of the investigation was to study the clinical efficacy of the immunomodulatory drug Polyoxidonium in the complex treatment of cervical intraepithelial neoplasia (CIN) of the 1st degree associated with PVI.Materials and Methods When visiting a gynecologist, the patients were included in the study according to the protocol, based on the results of screening, in accordance with the inclusion and exclusion criteria. Study inclusion criteria. Nosological form of the disease: CIN 1st degree associated with PVI; the duration of the disease is from 1 month to 1 year; lack of immunomodulatory and antiviral therapy prior to study selection; age 18-45; height, body weight without restrictions; race, nationality, profession without restrictions.Exclusion criteria from the study: pregnancy; unacceptable concomitant diseases: decompensated extragenital pathology. Examination and treatment of 60 patients (main group) aged 18 to 45 years with an established histological diagnosis of CIN of the 1st degree, in whom HPV of high oncogenic risk of 16 and 18 types was previously detected by PCR … All patients underwent a standard examination, including: cytological examination of smears from the ecto- and endocervix, extended colposcopy, histological examination of cervical biopsies, examination of the contents of the vagina and cervical canal for viral, bacterial, protozoal agents by the method PCR.To study local immunity in the contents of the vagina and cervical canal, the levels of secretory immunoglobulin A (sIgA), interferon (IFN) -a, IFN-g, interleukin (IL) -1b, IL-10, tumor necrosis factor ( TNF) a using the Vector-Best test systems (Novosibirsk). The material was taken from the posterior fornix of the vagina and the cervical canal, the contents were dissolved in 5 ml of saline, centrifuged, and the supernatant was examined. After the examination, the patients of the main group were divided into 2 groups of 30 women each.The distribution of patients into groups (1 and 2) was carried out randomly – by the method of random sampling. When distributing patients into groups, stratification was carried out according to the risk of complications. The study used the parallel group method. Patients of the 1st group received treatment with the immunomodulatory drug Polyoxidonium, 1 suppository intravaginally, once a day for 10 days. After the treatment, the parameters of local immunity of the contents of the vagina and cervical canal, extended colposcopy, biopsy in the presence of abnormal colposcopic pictures were re-examined.With the newly confirmed histological diagnosis of grade 1 CIN, the patients underwent destructive treatment. Group 2 (comparison group) included 30 patients who, after the diagnosis of “CIN of the 1st degree associated with PVI,” underwent traditional therapy – destructive treatment. After destruction, to monitor the effectiveness of therapy, a repeated examination was carried out after 2 weeks, 1 month, extended colposcopy – after 2 months. parameters of local immunity in patients with HPV-associated cIN before and after treatment parameters of local immunity Patient groups, m ± m 1st (n = 30) 2nd (n = 30) Control group (n = 20) before treatment after treatment before sIgA treatment, mg / l 1.66 ± 0.34 * 5.85 ± 1.37 1.66 ± 0.34 * 6.69 ± 0.59 TNF, ng / ml 30.88 ± 2.78 * 20.48 ± 3.54 29.88 ± 2.78 * 21.81 ± 2.46 IFN-g, ng / ml 8.13 ± 1.23 * 15.96 ± 1.56 8.13 ± 1, 23 * 18.85 ± 2.23 IFN-a, ng / ml 3.79 ± 0.46 * 9.24 ± 1.78 3.79 ± 0.46 * 14.56 ± 1.86 IL-1b, ng / ml 145.13 ± 7.81 * 20.74 ± 2.18 140.13 ± 6.6 * 18.34 ± 2.35 IL-10, ng / ml 0.65 ± 0.12 * 1, 47 ± 0.13 0.70 ± 0.09 * 1.42 ± 0.15 * Significant differences with the control group.The control group consisted of 30 women with visually unchanged cervix, for whom the indicated parameters of local immunity were also determined. The duration of the study was 6 months. Throughout the study, it was unacceptable to take antibacterial, other immunomodulating antiviral drugs. Results of the study The surveyed women in the groups were comparable in terms of age, parity, and the development of menstrual function. The average age of all surveyed women was 34.2 ± 2.8 years.The patients of the main group were characterized by early sexual debut in 31.6%, in the control group – in 20% (p <0.05). HPV typing made it possible to identify type 16 in 45% of the examined patients in the main group, in 38% - in 18th, 8% - in 31st, 9% - in 51st, 2 or more types of the virus were observed in 8 (13.3 %) of patients with 1st degree CIN. In the control group, HPV carriage was detected in 4 (13.3%) patients, while oncogenic types 16 and 18 were found in 1 woman. The combination of PVI with other infectious agents in the main group was found in 42 (70.0%) women, which is consistent with the data of domestic and foreign researchers and may indicate a violation of local protective mechanisms [13].When identifying pathogens, chlamydial infection in the genital tract was detected in 5 (16.6%) patients of the main group and 4 (13.3%) women in the control group, the differences are statistically insignificant. Violations of the vaginal microbiocenosis in the form of anaerobic dysbiosis were observed in 20 (66.6%) and 7 (23.3%) women in the study and control groups, respectively (p <0.05). Mycoplasma hominis and Ureaplasma spp. were detected in a titer exceeding 103 CFU / ml in 26.6% of all patients, fungi of the genus Candida - in 30.0% of the examined women of the main group, in a significant titer in patients of the control group mycoplasma and fungi of the genus Candida were detected in 5 ( 16.6%) and 4 (13.3%) patients, respectively, which significantly differed from the indicators in the main group.The combination of HPV with persistent herpes infection (HSV type 2) was observed in 7 (23.3%) and 3 (10.0%) patients of the main and control groups, respectively (p <0.05). The combination of HPV with cytomegalovirus infection - in 30% of all examined patients of the main group, which is confirmed by the data of foreign researchers [15]. During colposcopic examination, abnormal colposcopic pictures were observed in 38 (63.3%) examined patients of the main group: acetone epithelium was detected in 7 cases, which was 18.4% of the number of abnormal colposcopy, puncture was noted in 6 (15, 7%) patients, mosaic - in 9 (23.7%) women, iodine-negative zone - in 21 (55.2%) cases.Histological examination in all patients of the main group confirmed a low severity intraepithelial lesion of the cervix. At the same time, a combination with other pathological processes was revealed: dyskeratosis was observed in 4 (13.3%) and 5 (16.6%) patients of groups 1 and 2, respectively, hyperplasia of cells of the basal and parabasal layers of the epithelium - in 6 (20.0%) and 7 (23.3%) patients of groups 1 and 2, respectively, acanthosis - in 4 (30.0%) and 5 (26.6%) patients of groups 1 and 2, respectively, hyperkeratosis - in 3 (10.0%) and 4 (13.3%) patients of groups 1 and 2, respectively.The investigated parameters of local immunity in patients with HPV-associated CINs were characterized by certain features presented in the table. Changes in local immunity were characterized by a significant increase in the indicators of the proinflammatory cytokine IL-1b and TNF, which is typical for the activation of opportunistic microflora and macrophage-phagocytic immunity [1, 3]. At the same time, the indices of nonspecific anti-infectious protection, represented by sIgA, significantly decreased, the indicator of anti-inflammatory cytokines (IL-10) and interferon status (IFN-a and IFN-g) also decreased, since the E7 protein secreted by HPV , has an immunosuppressive effect on interferon status at the local level.After receiving the results of histological examination, morphological confirmation of intraepithelial lesion and examination of the local immunity of the cervical canal before the destructive method of treatment, patients of the 1st group underwent a course of immunomodulatory therapy with Polyoxidonium, 1 suppository 12 mg 1 time per intravaginal day No. 10. The studied parameters of local immunity after the therapy were characterized by the normalization of indicators, while the increased indicators of the proinflammatory cytokines IL-1b and TNF decreased by 7.25 and 1.54 times, respectively, their values ​​after therapy did not differ from those in the control group. ...Decreased parameters of anti-inflammatory cytokine IL-10, interferon status increased, their values ​​after treatment were comparable with those of the control group (see table). The results of the control colposcopy one month after immunomodulatory therapy demonstrated a normal colposcopic picture in 13 (43.3%) patients; there was no need for destructive treatment in these women after drug correction of local immunity. Colposcopy revealed metaplastic epithelium in the transformation zone in 13 patients of group 1 after Polyoxidonium therapy, after 30 days - stratified squamous epithelium, no destructive treatment was required.17 patients of the 1st group and all patients of the 2nd group underwent destructive treatment of the cervix. For destruction, the methods of argon plasma ablation were used. The period of epithelialization took place in patients of the 1st group without complications; complete epithelialization was observed 3 weeks after treatment. In group 2, in 4 patients, epithelialization was complicated by the addition of an inflammatory process, in 2 - by bleeding. Recurrence of the process within 3 months was detected in 4 patients of the 2nd group. 6 months after the complex therapy, HPV elimination was noted in 24 (80.0%) patients of group 1 and in 14 (46.6%) patients in group 2 (p <0.05).Conclusions Cervical neoplasias associated with PVI are characterized by impaired local immune status. Violations of the cytokine profile are manifested in an increase in the values ​​of proinflammatory cytokines and tumor necrotic factor and in a decrease in the indices of anti-inflammatory cytokines and interferon status. Considering that the use of the local immunomodulatory drug Polyoxidonium in the form of suppositories in every third patient led to a regression of the neoplastic process without destructive treatment, in 85% of cases - to the normalization of local immunity, a decrease in recurrence and an acceleration of epithelialization after destruction, elimination of HPV, for the treatment of cervical neoplasias associated with PVI, it is advisable to include this drug in the complex therapy of CIN 1st degree before destructive methods of treatment.

  1. Kondrikov N.I. Cervical pathology: morphology, physiology, diagnostics, fundamentals of therapy. M .: Practice. medicine, 2008.
  2. Minkina G.N. Monitoring of cervical intraepithelial neoplasias. Cervical pathology and genital infections. M .: MEDpress – inform, 2008; with. 8-15.
  3. Prilepskaya V.N. Cervical pathology and genital infections.M .: MEDpress – inform, 2008; with. 385.
  4. Sukhikh G.T., Prilepskaya V.N. Prevention of cervical cancer. A guide for doctors. M .: MEDpress – inform, 2012; with. 192.
  5. Dolgushina V.F., Telesheva L.F., Akhmatova A.N. et al. Clinical and immunological substantiation of immunotropic therapy of chronic cervicitis associated with human papillomavirus infection. Ural honey. zhurn. 2009; 3 (57): 58-62.
  6. Rogovskaya S.I. Human papillomavirus infection in women and cervical pathology: to help the practitioner.M .: GEOTAR-Media, 2008; with. 192.
  7. Centers for Disease Control and Prevention, Sexually Transmitted Diseases Treatment Guidelines, 2010; p. 22.
  8. Stern P.L. Immune control of human papilloma virus (HPV) associated anogenital disease and potential for vaccination. J Clin Virology 2005; 32S1: 72-81.
  9. Desruisseau A. J et al. Epidemiology of HPV in HIV-positive and HIV-negative fertile women in Cameroon, West Africa.Infect Dis Obstet Gynecol 2009: 8105-96.
  10. Abramovskikh O.S., Dolgushina V.F., Zotova M.A. Functional activity of neutrophils and the level of cytokines in cervical mucus in HPV-associated pathology of the cervix. Immunology. 2011; 32 (2): 143-6.
  11. Voroshilina E.S., Tumbinskaya L.V., Donnikov A.E. Vaginal biocenosis in terms of quantitative PCR: what is the norm? Akush. and gynecol. 2011; 1: 57-65.
  12. Grigorieva I.H. The use of antiviral and immunomodulatory drugs in patients with pre-invasive cervical cancer. Materials of the XI Russian Oncological Congress. M., 2007.
  13. Karatyuk T.I. Clinical and diagnostic features of cervical intraepithelial neoplasias associated with human papillomavirus infection. Abstract of thesis. dis. … Cand. honey. sciences. Omsk, 2011; with. 24.
  14. Abramovskikh O.S., Dolgushina V.F., Zotova M.A. Functional activity of neutrophils and the level of cytokines in cervical mucus in HPV-associated pathology of the cervix.Immunology. 2011; 32 (2): 143-6.
  15. Kiselev V.I., Apolikhina I.A., Muizhnek E.L., Denisova E.D. Pathogenetic approaches to the treatment of HPV-associated diseases of the cervix. M .: MEDpress – inform, 2008; with. 87-93.

Abstract – 55

PDF (Russian) – 9


Article Metrics


  • There are currently no refbacks.

Urology »Pelvic floor dysfunction in women in terms of genetic research

1. Ellerkmann R.M., Cundiff G.W., Melick C.F., Nihira M.A., Leffler K., Bent A.E. Correlation of symptoms with location and severity of pelvic organ prolapse. Am J Obstet Gynecol. 2001; 185 (6): 1332-1337.

2. Nygaard I., Barber M. D., Burgio K. L., Kenton K., Meikle S., Schaffer J., Spino C., Whitehead W. E., Wu J., Brody D. J; Pelvic Floor Disorders Network.Prevalence of symptomatic pelvic floor disorders in US women. JAMA 2008; 300: 1311-1316.

3. Haylen B. T., De Ridder D., Freeman R. M., et al. An International Urogynecological Association (IUGA) / International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010; 29: 4–20.

4. Fritel X., Varnoux N., Zins M., Breart G., Ringa V. Symptomatic pelvic organ prolapse at midlife, quality of life, and risk factors. Obstet Gynecol.2009; 113 (3): 609-616.

5. Gvozdev M.Yu., Pushkar ‘D.Yu., Tupikina N.V. Questionnaires as a tool to assess the quality of life of the urogynecological patients. Rossiiskii vestnik akushera-ginekologa. 2013; 1391: 23-30. Russian (Gvozdev M.Yu., Pushkar D.Yu., Tupikina N.V. Questionnaires as a tool for assessing the quality of life of a urogynecological patient. Russian Bulletin of Obstetrician-Gynecologist. 2013; 1391: 23–30).

6. Adjoussou S.A., Bohoussou E., Bastide S., Letouzey V., Fatton B., de Tayac R. Functional symptoms and associations of women with genital prolapse. Prog Urol. 2014; 24 (8): 511-517.

7. Burgio K.L., Matthews K.A., Engel B.T. Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women. J Urol 1991; 146: 1255-1259.

8. Lawrence J.M., Lukacz E.S., Nager C.W., Hsu J.W.Y., Luber K.M. Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women. Obstet Gynecol 2008; 111: 678-685.

9.Apolikhina I.A., Adikyan V.M. Epidemiological aspects of urinary incontinence. Zhurnal Rossiiskogo obshchestva akusherov-ginekologov. 2005; 1: 12. Russian (Apolikhina I.A., Adikyan V.M. Epidemiological aspects of urinary incontinence. Journal of the Russian Society of Obstetricians and Gynecologists. 2005; 1: 12).

10. Gvozdev M.Yu., Pushkar ‘D.Yu., Kasyan G.R. et al. Stress urinary incontinence in patients with pelvic organ prolapse. Endoskopicheskaya khirurgiya. 2013; 19 (4): 87–94. Russian (Gvozdev M.Yu., Pushkar D.Yu., Kasyan G.R. etc. Stress urinary incontinence in patients with prolapse and prolapse of the pelvic organs. Endoscopic Surgery. 2013; 19 (4): 87–94).

11. Adamyan L.V., Smol’nova T.Yu., Sidorov V.V. Laser Doppler flowmetry to study the microvasculature of patients with genital neoplasms. Voprosy ginekologii, akusherstva i perinatologii. 2006; 5: 34–39. Russian (Adamyan L.V., Smolnova T.Yu., Sidorov V.V. Laser Doppler flowmetry in the study of the state of the microvasculature in patients with tumor diseases of the genitals.Questions of gynecology, obstetrics and perinatology. 2006; 5: 34–39).

12. Krasnopol’skii V.I., Buyanova S.N., Shchukina N.A. et al. Surgical treatment of patients with prolapse of internal genital organs, and the prevention of vaginal prolapse after hysterectomy. Rossiiskii vestnik akushera-ginekologa. 2006; 6 (4): 66–71. Russian (Krasnopolskiy V.I., Buyanova S.N., Shchukina N.A. et al. Surgical treatment of patients with prolapse and prolapse of internal genital organs and prevention of prolapse of the vaginal dome after hysterectomy.Russian Bulletin of Obstetrician-Gynecologist. 2006; 6 (4): 66-71).

13. Samuelsson E.C., Victor F.T., Tibblin G., Svardsudd K.F. Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. Am. J. Obstet. Gynecol. 1999; 180 (2 Pt l): 299-305.

14. Deeb M.E., Awwad J., Yeretzian J.S., Kaspar H.G. Prevalence of reproductive tract infections, genital prolapse, and obesity in a rural community in Lebanon. Bull World Health Organ. 2003; 81 (9): 639-645.

15. Tegerstedt G., Maehle-Schmidt M., Nyrén O., Hammarström M. Prevalence of symptomatic pelvic organ prolapse in a Swedish population. Int Urogynecol J Pelvic Floor Dysfunct. 2005; 16 (6): 497-503.

16. Radzinskii V.E., Durandin Yu.M., Gagaev Ch.G., Toktar L.R., Marilova N.A., Totchiev G.F., Shalaev O.N. Perineology: diseases of the female perineum in obstetric-gynecologic, sexological, urologic, proctologic aspects. Ed. V.E. Radzinskii. M., 2006; 336 p. Russian (Radzinsky V.E., Durandin Yu.M., Gagaev Ch.G., Toktar L.R., Marilova N.A., Totchiev G.F., Shalaev O.N. Perineology: Diseases of the female perineum in obstetric-gynecological, sexological, urological, proctological aspects. Edited by V.E. Radzinsky. M., 2006; 336 s.).

17. Schaffer J.I., Bloom S.L. A randomized trial of the effects of coached vs uncoached maternal pushing during the second stage of labor on postpartum pelvic floor structure and function. Am J Obstet Gynecol. 2005; 192 (5): 1692-1696.

18. Mikhal’chuk N.S., Prudko A.Yu., Nechiporenko N.A. The anatomical and functional condition of the kidneys and urinary tract in women with genital prolapse. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2012; 4 (40): 46–49. Russian (Mikhalchuk N.S., Prudko A.Yu., Nechiporenko N.A. Anatomical and functional state of the urinary tract and kidneys in women with genital prolapse. Journal of Grodno State Medical University. 2012; 4 (40): 46–49) …

19.Lowder J.L., Frankman E.A., Ghetti C., Burrows L.J., Krohn M.A., Moalli P., Zyczynski H. Lower urinary tract symptoms in women with pelvic organ prolapse. Int Urogynecol J. 2010; 21 (6): 665-672.

20. Krissi H., Halperin R., Koren P., Peled Y. The presence and location of estrogen and progesterone receptors in the human pelvic cardinal ligaments. Pelviperineology. 2010; 29: 17-19.

21. Progetto Menopausa Italia Study Group. Risk factors for genital prolapse in non-hysterectomized women around menopause: Results from a large cross-sectional study in menopausal clinics in Italy.Eur J Obstet Gynecol Reprod Biol. 2000; 93: 135-140.

22. Swift S., Woodman P., O’Boyle A., Kahn M., Valley M., Bland D., Wang W., Schaffer J. Pelvic Organ Support Study (POSST): the distribution, clinical definition , and epidemiologic condition of pelvic organ support defects. Am J Obstet Gynecol. 2005; 1929 (3): 795–806.

23. Nygaard I., Barber M.D., Burgio K.L., Kenton K., Meikle S., Schaffer J., Spino C., Whitehead W.E., Wu J., Brody D.J .; Pelvic Floor Disorders Network…. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008; 300 (11): 1311-1316.

24. Chiaffarino F., Chatenoud L., Dindelli M., Meschia M., Buonaguidi A., Amicarelli F., Surace M., Bertola E., Di Cintio E., Parazzini F. Reproductive factors, family history, occupation and risk of urogenital prolapse. Eur J Obstet Gynecol Reprod Biol. 1999; 82 (1): 63–67.

25. Sharma S., Walia I., Singh A. A case control study on uterine prolapse in a Chandigarh slum. Bull Postgrad Inst Med Educ Res Chandigarh.2003; 37: 143-148.

26. Jack G.S., Nikolova G., Vilain E., Raz S., Rodríguez L.V. Familial transmission of genitovaginal prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2006; 17 (5): 498-501.

27. Hannestad Y.S., Rortveit G., Daltveit A.K., Hunskaar S. Are smoking and other lifestyle factors associated with female urinary incontinence? The Norwegian EPINCONT Study. BJOG. 2003; 110: 247-254.

28. McLennan M.T., Harris J.K., Kariuki B., Meyer S. Family history as a risk factor for pelvic organ prolapse.Int Urogynecol J Pelvic Floor Dysfunct. 2008; 19 (8): 1063-1069.

29. Miedel A., Tegerstedt G., Maehle-Schmidt M., Nyrén O, Hammarström M. Nonobstetric risk factors for symptomatic pelvic organ prolapse. Obstet Gynecol. 2009; 113 (5): 1089-1097.

30. Rodrigues A.M., Oliveira L.M., Martins Kde F., Del Roy C.A., Sartori M.G., Girão M.J., Castro Rde A. Risk factors for genital prolapse in a Brazilian population. Rev Bras Ginecol Obstet. 2009; 31 (1): 17–21.

31. Slieker-ten Hove M.C., Pool-Goudzwaard A.L., Eijkemans M.J., Steegers-Theunissen R.P., Burger C.W., Vierhout M.E. Symptomatic pelvic organ prolapse and possible risk factors in a general population. Am J Obstet Gynecol. 2009; 200 (2): 184 e1-7.

32. Altman D., Forsman M., Falconer C., Lichtenstein P. Genetic influence on stress urinary incontinence and pelvic organ prolapse. Eur Urol. 2008; 54 (4): 918-22.

33. Lince S.L., van Kempen L.C., Vierhout M.E., Kluivers K.B. A systematic review of clinical studies on hereditary factors in pelvic organ prolapse.Int Urogynecol J. 2012; 23 (10): 1327-1336.

34. Mothes A.R., Radosa M.P., Altendorf-Hofmann A., Runnebaum I.B. Risk index for pelvic organ prolapse based on established individual risk factors. Arch Gynecol Obstet. 2016; 293 (3): 617-624.

35. Buyanova S.N., Savel’ev S.V., Fedorov A.A. The role of the CTD in the pathogenesis of genital prolapse. Rossiiskii vestnik akushera-ginekologa. Spetsvypusk. 2008. P. 8-11. Russian (Buyanova S.N., Savelyev S.V., Fedorov A.A. The role of DST in the pathogenesis of genital prolapse.Russian Bulletin of Obstetrician-Gynecologist. Special issue. 2008. P. 8-11).

36. Kluivers K.B., Dijkstra J.R., Hendriks J.C., Lince S.L., Vierhout M.E., van Kempen L.C. COL3A1 2209G> A is a predictor of pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2009; 20 (9): 1113-1118.

37. Sukhikh G.T., Danilov A.Yu., Botasheva D.A. The role of immunohistochemical and genetic factors in clarifying the etiology and pathogenesis of genital prolapse in women. Rossiiskii vestnik akushera-ginekologa.2012; 2: 47-50. Russian (Sukhikh G.T., Danilov A.Yu., Botasheva D.A. The role of immunohistochemical and genetic factors in clarifying the etiology and pathogenesis of genital prolapse in women. Russian Bulletin of Obstetrician-Gynecologist. 2012; 2: 47–50).

38. Naftulovich R.A., Yashchuk A.G., Alakaeva D.R., Khusainova R.I. The role of hereditary factors in the occurrence of pelvic organs prolapse. Rossiiskii vestnik akushera-ginekologa. 2014; 1: 22-26. Russian (Naftulovich R.A., Yashchuk A.G., Alakaeva D.R., Khusainova R.I. The significance of hereditary factors in the occurrence of pelvic organ prolapse. Russian Bulletin of Obstetrician-Gynecologist. 2014; 1: 22-26).

39. Carley M.E., Schaffer J. Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers Danlos syndrome. Am J Obstet Gynec. 2000; 182 (5): 1021-1023.

40. Paladini D., Di Spiezio Sardo A., Mandato V.D., Guerra G., Bifulco G., Mauriello S., Nappi C. Association of cutis laxa and genital prolapse: a case report. Int Urogynecol J Pelvic Floor Dysfunct.2007; 18 (11): 1367-1370.

41. Naftulovich R.A., Yashchuk A.G., Maslennikov A.V., Alakaeva D.R. Features of family history in patients with pelvic organs prolapse. Rossiiskii vestnik akushera-ginekologa. 2013; 1: 30–36. Russian (Naftulovich R.A., Yashchuk A.G., Maslennikov A.V., Alakaeva D.R. Features of family history in patients with prolapse and prolapse of the pelvic organs. Russian Bulletin of Obstetrician-Gynecologist. 2013; 1: 30– 36).

42. Salter S.A., Batra R.S., Rohrer T.E., Kohli N., Kimball A.B. Striae and pelvic relaxation: two disorders of connective tissue with a strong association. J Invest Dermatol. 2006; 126: 1745-1748.

43. Lammers K., Lince S.L., Spath M.A., van Kempen L.C., Hendriks J.C., Vierhout M.E., Kluivers K.B. Pelvic organ prolapse and collagen-associated disorders. Int Urogynecol J. 2012; 23: 313-319.

44. Lee S.W., Cho H.H., Kim M.R., You Y.O., Kim S.Y., Hwang Y.B., Kim J.H. Association between pelvic organ prolapse and bone mineral density in postmenopausal women.J Obstet Gynaecol. 2015; 35 (5): 476-480.

45. Veit-Rubin N., Cartwright R., Singh A.U., Digesu G.A., Fernando R., Khullar V. Association between joint hypermobility and pelvic organ prolapse in women: a systematic review and meta-analysis. Int Urogynecol J. 2015.

46. http://www.cdc.gov/genomics/hugenet/hugenavigator.htm

47. Jackson S.R., Avery N.C., Tarlton J.F., Eckford S.D., Abrams P., Bailey A.J. Changes in metabolism of collagen in genitourinary prolapse.Lancet. 1996; 347 (9016): 1658-1661.

48. Fadeev A.S., Levachev S.M., Izmailova V.N. Monomolecular layers of collagen. Vestnik Moskovskogo universiteta. Seriya 2: Khimiya. 1999; 40 (4): 270-275. Russian (Fadeev A.S., Levachev S.M., Izmailova V.N. Monomolecular layers of collagen. Bulletin of Moscow University. Series 2: Chemistry. 1999; 40 (4): 270–275).

49. Lim V.F., Khoo J.K., Wong V., Moore K.H. Recent studies of genetic dysfunction in pelvic organ prolapse: the role of collagen defects.Aust N Z J Obstet Gynaecol. 2014; 54 (3): 198–205.

50. Mann V., Hobson E.E., Li B., Stewart T.L., Grant S.F., Robins S.P., Aspden R.M., Ralston S.H. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest. 2001; 107 (7): 899-907.

51. Ward R.M., Velez Edwards D.R., Edwards T., Giri A., Jerome R.N., Wu J.M. Genetic epidemiology of pelvic organ prolapse: a systematic review. Am J Obstet Gynecol. 2014; 211 (4): 326–335.

52. Cartwright R., Kirby AC, Tikkinen KA, Mangera A., Thiagamoorthy G., Rajan P., Pesonen JS, Ambrose C., Gonzalez-Maffe J., Bennett P., Palmer T., Walley A. , Järvelin MR, Chapple C., Khullar V. Systematic review and meta-analysis of genetic association studies of urinary symptoms and prolapse in women. Am J Obstet Gynecol. 2015; 212 (2): 199.e1-199.e24.

53. Khadzhieva M.B., Kamoeva S.V., Ivanova A.V., Abilev S.K., Sal’nikova L.E. Polymorphism of genes controlling elastogenesis and the risk of pelvic organs prolapse in women.Genetika. 2015; 51 (10): 1191-1198. Russian (Khadzhieva M.B., Kamoeva S.V., Ivanova A.V., Abilev S.K., Salnikova L.E. Polymorphism of genes that control elastogenesis processes and the risk of pelvic organ prolapse in women. Genetics. 2015 ; 51 (10): 1191-1198).

54. Liang C.C., Huang H.Y., Tseng L.H. et al. Expression of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 (TIMP-1, TIMP-2 and TIMP-3) in women with uterine prolapse but without urinary incontinence. Eur J Obstet Gynecol Reprod Biol.2010; 153: 94–98.

55. Budatha M., Roshanravan S., Zheng Q., Weislander C., Chapman SL, Davis EC, Starcher B., Word RA, Yanagisawa H. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans … J Clin Invest. 2011; 121: 2048–2059.

56. Dviri M., Leron E., Dreiher J., Mazor M., Shaco-Levy R. Increased matrix metalloproteinases-1, -9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol.2011; 156: 113-117.

57. Alarab M., Kufaishi H., Lye S., Drutz H., Shynlova O. Expression of extracellular matrix-remodeling proteins is altered in vaginal tissue of premenopausal women with severe pelvic organ prolapse. Reprod Sci. 2014; 21 (6): 704-715.

58. Wang X., Li Y., Chen J., Guo X., Guan H., Li C. Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse. Mol Med Rep.2014; 10 (4): 2004-2008.

59. Skorupski P., Jankiewicz K., Miotła P., Marczak M., Kulik-Rechberger B., Rechberger T. The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse. Int Urogynecol J. 2013; 24 (6): 1033-1038.

60. Chen C., Hill L. D., Schubert C. M., Strauss J. F. 3rd, Matthews C.A. Is laminin gamma-1 a candidate gene for advanced pelvic organ prolapse? Am J Obstet Gynecol. 2010; 202 (5): 505.e1-5.

61 Nikolova G., Lee H., Berkovitz S., Nelson S., Sinsheimer J., Vilain E., Rodríguez L.V. Sequence variant in the laminin gamma1 (LAMC1) gene associated with familial pelvic organ prolapse. Hum Genet. 2007; 120 (6): 847–856.

62. Wu J.M., Visco A.G., Grass E.A., Craig D.M., Fulton R.G., Haynes C., Weidner A.C., Shah S.H. Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse. Obstet Gynecol. 2012; 120 (3): 587-593.

63. Jepsen K.J., Wu F., Peragallo J.H., Paul J., Roberts L., Ezura Y., Oldberg A., Birk D.E., Chakravarti S. A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice. J. Biol. Chem. 2002; 277 (38): 3553–35540.

64. Söderberg M.W., Byström B., Kalamajski S., Malmström A., Ekman-Ordeberg G. Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse. Mol. Hum. Reprod. 2009; 15 (4): 251–257.

65. Chen H.Y., Chung Y.W., Lin W.Y., Chen W.C., Tsai F.J., Tsai C.H. Estrogen receptor alpha polymorphism is associated with pelvic organ prolapse risk. Int Urogynecol J Pelvic Floor Dysfunct. 2008; 19 (8): 1159-1163.

66. Chen H.Y., Chung Y.W., Lin W.Y., Chen W.C., Tsai F.J., Tsai C.H. Progesterone receptor polymorphism is associated with pelvic organ prolapse risk. Acta Obstet Gynecol Scand. 2009; 88 (7): 835-838.

67. Chen H.Y., Wan L., Chung Y.W., Chen W.C., Tsai F.J., Tsai C.H. Estrogen receptor beta gene haplotype is associated with pelvic organ prolapse.Eur J Obstet Gynecol Reprod Biol. 2008; 138: 105-109.

68. Li E.S., Kappusheva L.M., Karaeva K.Yu. Results of surgical treatment of genital prolapse. Implications of polymorphisms of collagen type III genes and estrogen receptor alpha. Doktor. Ru. Ginekologiya Endokrinologiya. 2015; 11 (112): 29–34. Russian (Li ES, Kappusheva LM, Karaeva K.Yu. Results of surgical treatment of genital prolapse. Significance of polymorphisms of genes for collagen type III and estrogen receptor alpha. Dr. Ru.Gynecology Endocrinology. 2015; 11 (112): 29–34).

69. Kamoeva C.V., Savchenko T.N., Ivanova A.V., Abaeva Kh.A. Contemporary genetic aspects of pelvic organ prolapse in women .. Akusherstvo, ginekologiya i reproduktsiya. 2013; 7 (1): 17–21. Russian (Kamoeva S.V., Savchenko T.N., Ivanova A.V., Abaeva Kh.A. Modern genetic aspects of pelvic organ prolapse in women. Obstetrics, gynecology and reproduction. 2013; 7 (1): 17–21 ).

70. Drewes P.G., Yanagisawa H., Starcher B., Hornstra I., Csiszar K., Marinis S.I., Keller P., Word R.A. Pelvic organ prolapse in Fibulin-5 knockout mice: pregnancy changes in elastic fiber homeostasis in mouse vagina. Am J Pathol. 2007; 170 (2): 578-589.

71. Liu X., Zhao Y., Pawlyk B., Damaser M., Li T. Failure of elastic fiber homeostasis leads to pelvic floor disorders. Am J Pathol. 2006; 168 (2): 519-528.

72. Yamamoto K., Yamamoto M., Akazawa K., Tajima S., Wakimoto H, Aoyagi M. Decrease in elastin gene expression and protein synthesis in fibroblasts derived from cardinal ligaments of patients with prolapsus uteri.Cell Biol Int. 1997; 21: 605-611.

73. Karam J.A., Vazquez D.V., Lin V.K., Zimmern P.E. Elastin expression and elastic fiber width in the anterior vaginal wall of postmenopausal women with and without prolapse. BJU Int. 2007; 100 (2): 346-350.

74. Nakamura T., Lozano PR, Ikeda Y., Iwanaga Y., Hinek A., Minamisawa S., Cheng CF, Kobuke K., Dalton N., Takada Y., Tashiro K., Ross Jr J. , Honjo T., Chien KR Fibulin-5 / DANCE is essential for elastogenesis in vivo. Nature. 2002; 10; 415 (6868): 171-175.

75. Klutke J., Ji Q., ​​Campeau J., Starcher B., Carlos Felix J., Stanczyk F.Z., Klutke C. Decreased endopelvic fascia elastin content in uterine prolapse. Acta Obstetricia et Gynecologica. 2008; 87: 111-115.

76. Northington G.M. Fibulin-5: two for the price of one maintaining pelvic support. J Clin Invest. 2011; 121 (5): 2048-2059.

77. Zhao B.H., Zhou J.H. Decreased expression of elastin, fibulin-5 and lysyl oxidase-like 1 in the uterosacral ligaments of postmenopausal women with pelvic organ prolapse.J Obstet Gynaecol Res. 2012; 38: 925-931.

78. Zhou Y., Ling O., Bo L. Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction. J Biomed Res. 2013; 27: 23-28.

79. Wieslander C.K., Rahn D.D., McIntire D.D., Acevedo J.F., Drewes P.G., Yanagisawa H., Word R.A. Quantification of Pelvic Organ Prolapse in Mice: Vaginal Protease Activity Precedes Increased MOPQ Scores in Fibulin 5 Knockout Mice.Biol Reprod. 2009; 80 (3): 407-414.

80. Ji Q.S., Qi B., Wen Y.C. et al. The association of LOXL1 polymorphisms with exfoliation syndrome / glaucoma: Meta-analysis. Int J Ophthalmol. 2015; 8 (1): 148-156.

81. Liu X., Zhao Y., Gao J., Pawlyk B., Starcher B., Spencer J.A., Yanagisawa H., Zuo J., Li T. Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet. 2004; 36 (2): 178-182.

82. Ferrell G., Lu M., Stoddard P. A single nucleotide polymorphism in the promoter of the LOXL1 gene and its relationship to pelvic organ prolapse and preterm premature rupture of membranes.REPROD SCI. 2009; 16 (5): 438–446.

83. Chen H.Y., Lu Y., Qi Y., Bai W.P., Liao Q.P. Relationship between the expressions of mitofusin-2 and procollagen in uterosacral ligament fibroblasts of postmenopausal patients with pelvic organ prolapse.