Polycystic Ovary Syndrome

Other names for this syndrome are as follows:

• polycystic ovary disease (incorrectly, since this condition is not characterized as a disease , a separate nosological form, but as a clinical syndrome , the causes of which may be different);
• functional ovarian hyperandrogenism (or functional ovarian hyperandrogenism);
• hyperandrogenic chronic anovulation ;
• ovarian dysmetabolic syndrome;
• polycystic ovary syndrome;
• polycystic ovary.

There are two of the most common in clinical practice, the definition of polycystic ovary syndrome.

The first definition was worked out in 1990 by consensus of an expert commission formed by the American National Institutes of Health (NIH). According to this definition, the patient should be diagnosed with polycystic ovary, if she is simultaneously present:

1. Symptoms of excessive activity or excessive secretion of androgens (clinical and / or biochemical);
2. Oligovulation or Anovulation

and if this excludes other causes that can cause polycystic ovarian disease.

The second definition was formulated in 2003 by the consensus of European experts, formed in Rotterdam ^[3] . By this definition, a diagnosis is made if the patient has at the same time any two of the following three symptoms:

1. Symptoms of excessive activity or excessive secretion of androgens (clinical or biochemical);
2. Oligo-ovulation or anovulation;
3. Polycystic ovaries with ultrasound examination of abdominal organs

and if this excludes other causes that can cause polycystic ovarian disease.

The Rotterdam definition is much broader and includes significantly more patients in the group suffering from this syndrome. In particular, it includes patients without clinical or biochemical signs of an excess of androgens (since any two of the three signs are obligatory, not all three), while in the American definition excessive secretion or excessive activity of androgens is a prerequisite for the diagnosis polycystic ovary. Critics of the Rotterdam definition argue that the findings obtained in the study of patients with an excess of androgens, can not necessarily be extrapolated to patients without symptoms of an excess of androgens ^{[4] [5]} .

The common symptoms of polycystic ovary are as follows:

• Oligomenorrhea , amenorrhea - irregular, rare menstruation or the complete absence of menstruation; those menstruation, which still occur, can be pathologically scanty or, on the contrary, excessively abundant, as well as painful;
• Infertility , usually resulting from chronic anovulation or oligoovulation (complete absence of ovulation or ovulation does not occur in every cycle);
• Elevated blood levels of androgens (male hormones), especially the free fractions of testosterone , androstenedione, and dehydroepiandrosterone sulfate , which causes hirsutism and sometimes masculinization ^[6] ;
• Central obesity - “arachnid” or “apple-shaped” male-type obesity , in which the bulk of adipose tissue concentrates in the lower abdomen and in the abdominal cavity;
• Androgenic alopecia (significant alopecia or male-type hair loss with bald areas on the sides of the forehead , at the crown, due to hormonal imbalance);
• Acne , oily skin, seborrhea ;
• Acanthosis (dark pigmentation on the skin, from light beige to dark brown or black);
• Acrochordons (skin folds) - small folds and wrinkles of the skin;
• The appearance of stretch marks (stretch bands) on the skin of the abdomen, thighs, buttocks, as a result of rapid weight gain against the background of hormonal imbalance;
• Long periods of symptoms resembling the symptoms of premenstrual syndrome ( edema , mood swings, lower abdominal pain, lower back pain, or swelling of the mammary glands);
• Sleep apnea - respiratory standstill in sleep, leading to frequent night awakenings of the patient;
• Depression , dysphoria (irritability, nervousness, aggressiveness ), often drowsiness, lethargy, apathy , complaints of "fog in the head."
• Multiple ovarian cysts. Sonographically, they may look like a “pearl necklace,” a cluster of whitish bubbles or “fruit pits” scattered throughout the ovarian tissue;
• The increase in the size of the ovaries 1.5-3 times due to the occurrence of many small cysts
• Thickened, smooth, pearl-white outer surface (capsule) of the ovaries;
• A thickened, hyperplastic endometrium of the uterus is the result of a prolonged excess of estrogens not balanced by adequate progesterone effects;
• Chronic pain in the lower abdomen or in the lower back, in the pelvic region, probably due to compression of the pelvic organs by enlarged ovaries or due to prostaglandin hypersecretion in the ovaries and endometrium; the exact cause of chronic pain in polycystic ovaries is unknown;
• Elevated LH or elevated LH / FSH ratio: when measured on the 3rd day of the menstrual cycle, the LH / FSH ratio is greater than 1: 1;
• Low levels of globulin binding sex steroids ;
• Hyperinsulinemia (elevated level of insulin in the blood), impaired glucose tolerance , signs of tissue insulin resistance when tested by the sugar curve method ^[7] .

Women suffering from polycystic ovaries are at increased risk of developing the following complications:

• Endometrial hyperplasia and endometrial cancer due to the absence or irregularity of menstruation and the “accumulation” of unhealed endometrium, as well as due to the absence or insufficiency of progesterone effects leading to prolonged unbalanced progesterone overstimulation of endometrial cells with elevated estrogen levels;
• Breast cancer ;
• Obesity ;
• Insulin resistance and type 2 diabetes mellitus ;
• high blood pressure ;
• Thrombosis , thromboembolism, thrombophlebitis due to increased blood clotting;
• Dyslipidemia (metabolic cholesterol and triglycerides with the possible development of vascular atherosclerosis );
• Cardiovascular diseases , myocardial infarction , stroke .

The data of a number of researchers indicate that women with polycystic ovaries have an increased risk of miscarriage or premature birth , miscarriage. In addition, many women with this syndrome cannot conceive or have difficulty conceiving due to the irregularity of the menstrual cycle and the lack of or rarely occurring ovulations. However, with proper treatment, these women can conceive, bear and give birth to a healthy baby.

Although during ultrasound examination of the abdominal cavity, ovaries that look like polycystic ones are found in up to 20% of women of reproductive age (including those without any complaints), only 5-10% of women of reproductive age show clinical signs allowing diagnosis of polycystic ovary syndrome . Polycystic ovary syndrome is equally common in different ethnic groups. It is the most frequent hormonal disorder in women of childbearing age and one of the leading causes of female infertility .

The exact causes of the syndrome are unknown, but great importance is attached to the pathological decrease in insulin sensitivity of peripheral tissues, especially adipose and muscle tissue (the development of their insulin resistance), while the insulin sensitivity of the ovarian tissue is preserved. The situation is also possible pathologically increased insulin sensitivity of the ovarian tissue while maintaining normal insulin sensitivity of peripheral tissues.

In the first case, as a result of the insulin resistance of the organism, compensatory hypersecretion of insulin occurs, leading to the development of hyperinsulinemia. A pathologically elevated level of insulin in the blood leads to ovarian hyperstimulation and increased ovarian androgen and estrogen secretion and impaired ovulation, since the ovaries maintain normal insulin sensitivity.

In the second case, the level of insulin in the blood is normal, however, the reaction of the ovaries to stimulation with normal insulin levels is pathologically increased, which leads to the same result — ovarian hypersecretion of androgens and estrogens and impaired ovulation.

Pathological insulin resistance of tissues, hyperinsulinemia, and insulin hypersecretion in polycystic ovaries often (but not always) are the result of obesity or overweight. However, these phenomena themselves can lead to obesity, since the effects of insulin are increased appetite, increased fat deposition and reduced mobilization.

In the pathogenesis of polycystosis of the ovaries, impairments of regulating hypothalamic-pituitary influences are also of importance: excessive LH secretion, an abnormally elevated LH / FSH ratio, increased “ opioidergic ” ^{[8] [9]} and reduced dopaminergic ^{[10] [11] [12]} tone in the system hypothalamus pituitary. The condition can be burdened and more difficult to treat in the presence of concomitant hyperprolactinemia , subclinical or clinically severe thyroid insufficiency. Such combinations are found in these women much more often than in the general population, which may indicate the polyendocrine or polyetiological nature of the Stein-Leventhal syndrome.

Some researchers attach importance to elevated levels of prostaglandins and other inflammatory mediators in the ovarian tissue and in the follicular fluid in patients with polycystic ovaries and believe that in the pathogenesis of polycystic ovary syndrome, the “cold”, aseptic inflammation of the ovarian tissue, which has been transferred, may play a role female genital inflammatory diseases or autoimmune mechanisms. It is known that the introduction of prostaglandin E1 into the ovary or into the vessel feeding it causes in laboratory rats a significant increase in the secretion of androgens and estrogens by the tissue of the ovary.

History

Historically, the very first attempts at treating polycystic ovary syndrome consisted of surgical intervention — ovarian decapsulation or partial resection with removal of tissue areas most affected by cytosis, or ovarian wedge resection of the ovarian bed, or in the careful application of diathermy (heating) of the ovaries. In some cases, such operations led to success and allowed the woman to restore fertility , as well as achieve a sharp decrease in the secretion of androgens by the ovaries, normalization of the menstrual cycle , etc. However, surgery is not always possible, and does not always lead to success. In addition, possible complications, such as the formation of adhesions. Therefore, experts were looking for conservative , non-surgical methods for the treatment of polycystic ovaries.

Traditional conservative treatment consisted in the prescription of anti- androgens , estrogens , progestins with anti-androgenic activity, or their combination (for example, in the form of birth control pills like Diane-35). Such treatment usually allowed to normalize the menstrual cycle, but had insufficient efficacy against skin manifestations ( acne , skin greasiness, androgen-dependent alopecia ), did not allow to restore ovulation and fertility, and did not eliminate the causes of polycystic ovarian disorder ( insulin secretion and insulin sensitivity) tissues, hypothalamic axis functions - pituitary , etc.). Moreover, treatment with estrogens, progestins and antiandrogens was often accompanied by a further increase in the weight of the patients, aggravation of the existing problems with carbohydrate metabolism and the thyroid gland, hyperprolactinemia , and depression .

The next attempt to improve the treatment of polycystic ovary syndrome was undertaken with the advent of anti-estrogenic drugs in the arsenal of doctors - clostilbegit (clomiphene citrate) and tamoxifen . The use of clomiphene citrate or tamoxifen in the middle of the cycle allowed, in about 30% of cases, to successfully induce ovulation, restore the fertility of women and achieve a stable ovulatory menstrual cycle without the use of exogenous hormones (estrogens, progestins and antiandrogens). However, the effectiveness of clostilbegit and tamoxifen regarding the remaining symptoms of polycystic ovary, in particular, manifestations of hyperandrogenism, was found to be limited. The effectiveness of combination therapy (estrogens and progestins or cycle antiandrogens, clostilbegit or tamoxifen in the middle of the cycle) was higher, but also insufficient.

Attempts to improve the effectiveness of treatment of women with polycystic ovarian syndrome by correcting for reliably existing or suspected concomitant endocrine disorders. was individual and not constant and predictable.

Real shifts in the effectiveness of treatment of polycystic ovarian disease occurred when it was possible to penetrate deeper into the understanding of the pathogenesis of polycystic ovarian disease and when they began to attach primary importance to the development of this state of insulin hypersecretion and the pathological insulin resistance of the ovaries. Since that time, treatment of polycystic ovaries has become widely used as first-line drugs, which normalize the sensitivity of tissues to insulin and lower insulin secretion - metformin , glitazone ( pioglitazone , rosiglitazone ). This approach was very successful - in 80% of women with polycystic ovarian monotherapy with metformin or one of the glitazones, ovulation was spontaneously restored, the menstrual cycle normalized, ovarian secretion of androgens decreased and hyperandrogenic symptoms diminished, body weight decreased, carbohydrate metabolism normalized, mental state decreased . Most of these women were then able to bear and give birth to healthy children.

An even higher success rate, exceeding 90%, was given by combination therapy - a combination of metformin or glitazones with previously known methods (estrogens, antiandrogens and progestins, and / or with anti-estrogens in the middle of the cycle and / or, possibly, correction of concurrent violations of prolactin secretion, thyroid hormones, adrenal androgens). Introduction to the practice of gynecologists-endocrinologists of such a combined approach to the treatment of polycystic ovarian disease has almost completely eliminated, except for rare multi-resistant cases, the need for surgical intervention for polycystic ovarian disease, and also to make it much more rare for ovulation to be induced using gonadotropins and artificial insemination of women with polycystic ovaries.

Current state of the issue

To date, first-line drugs in the treatment of polycystic ovaries are metformin and glitazone ( pioglitazone , rosiglitazone ). They can be attached, if necessary, antiandrogenic drugs ( cyproterone acetate ), estrogens ( ethinyl estradiol as a separate drug or in birth control pills), progestins , small doses of dexamethasone (0.5-1 mg in the evening to suppress the secretion of adrenal androgens).

Measures are needed to normalize body weight: diet, physical activity.

A promising direction for the effective and safe treatment of PCOS is the use of nutraceuticals (in particular, myo-inositol ). Myoinositol and its derivatives are necessary for the realization of the effects of GNVG , LH , FSH . The effects of myo-inositol in women with PCOS were studied in a systematic analysis of randomized controlled studies. In general, the results of the analysis allow us to recommend the use of myo-inositol for improving ovarian function, as well as metabolic and hormonal parameters in patients with PCOS ^[13] .

In the presence of concomitant hyperprolactinemia, its correction is indicated by the administration of bromocriptine . When a subclinical, and even more clinically severe, thyroid insufficiency is detected, it is subject to correction with the help of exogenous L-thyroxine.

If it is necessary to induce ovulation, if it is not restored spontaneously during therapy with metformin or glitazones, a woman can be assigned clostilbegit or tamoxifen in the middle of the cycle.

In the case of resistance to all applied methods of treatment, surgical operation (laser or diathermocoagulation of the ovaries or their decapsulation, partial resection) is indicated.

• Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352 : 1223-36. PMID 15788499 .

Medical Information

• Center for the Study of Polycystic Ovary Syndrome at the University of Chicago
• Introduction to the problem of polycystic ovaries by Dr. John Eden POSAA
• Polycystic Ovary Syndrome News and Infertility
• International Infertility Council - Frequently asked questions about polycystic ovary.
• The article "Hyperandrogenic States and Polycystic Ovary Syndrome".

Patient Support Groups

• Association of patients with polycystic ovaries in Australia
• Site for women of all ages suffering from polycystic ovaries
• British Polycystic Ovary Women Support Group
• International Association for the Advancement of Women with Polycystic Ovary Syndrome