
Definition of the Disease. Causes of the Condition
Polycystic ovary syndrome (PCOS) is a chronic condition in which a woman lacks or infrequently ovulates, meaning the mature egg does not exit the ovary for fertilization by sperm. Otherwise known as polycystic ovaries or Stein-Leventhal syndrome, it is accompanied by reproductive disturbances (difficulty conceiving and giving birth), metabolic disorders, and psychological issues.
PCOS is the most common endocrine disorder, affecting 5-20% of girls of reproductive age. It is identified by the presence of any two of the following main criteria:
- Excess male sex hormones produced in the ovaries, manifesting as external signs (seborrhea, male-pattern hair growth, acne, hair loss) and/or laboratory elevation of androgen levels;
- Prolonged absence of ovulation (oligoovulation) or complete lack thereof;
- Distinctive polycystic changes in the ovaries, detected through ultrasound examination (US) .
There are two significant theories regarding the development of PCOS:
- The theory of disruption in the production of hormones regulating ovarian function in the hypothalamus and pituitary gland. These brain regions are responsible for its neuroendocrine activity and the bodyโs overall function.
- The insulin resistance theory โ decreased sensitivity of the bodyโs cells to insulin, leading to disrupted glucose metabolism and its uptake by cells .
Both theories explain the complaints and laboratory changes observed in patients with polycystic ovaries.
The contribution of genetic factors to the development of PCOS is also discussed. Specifically, genes involved in the formation or action of male sex hormones, insulin signaling, metabolism, follicle formation in the ovary, and other processes are mentioned. For instance, there is a 30-50% risk of developing PCOS in a woman if her mother or sister has the condition.
Symptoms of Polycystic Ovary Syndrome
Symptoms of polycystic ovary syndrome (PCOS) include:
- Irregular menstrual cycle
- Abnormal uterine bleeding
- Infertility
- Symptoms of hyperandrogenism (excess male sex hormones)
- Overweight or obesity (body mass index of 25.0 and above)
- Acanthosis nigricans โ dark brown patches in skin folds of the neck, armpits, groin (an optional sign of insulin resistance)
- Psychological and psychosocial disturbances
- Eating disorders (overeating)
An irregular menstrual cycle is defined as:
- Cycle length exceeding 90 days in the first year after menarche (first menstruation)
- Cycle length less than 21 days or more than 45 days from the 1st to 2nd year after menarche
- Cycle length less than 21 days or more than 35 days or fewer than 8 cycles per year in women of reproductive age (from the 3rd year after menarche until menopause)
- Initial absence of menstruation at the age of 15 (primary amenorrhea) or absence for more than three years from the onset of breast development (telarche)
Approximately 20% of women with PCOS maintain a regular menstrual cycle without ovulation occurring. Therefore, judging ovulation solely based on cycle regularity is incorrect.
Abnormal uterine bleeding occurs when the thickened endometrium (inner layer of the uterus) is not fully shed regularly, leading to heavier and longer periods.
Infertility is reported to be 15 times more common in women with PCOS compared to those without this condition. In 70-75% of cases, it is primary infertility (if pregnancy has never occurred) and is associated with cycles where ovulation did not occur.
Symptoms of excess male sex hormones include:
- Seborrhea โ increased production of skin oil on the scalp, face, chest, back, and shoulders
- Hirsutism โ excessive growth of dark, coarse hair on the upper lip, chin, chest, back, abdomen, and inner thighs
- Acne โ skin condition related to the blockage of oil glands
- Androgen-dependent alopecia โ progressive hair loss starting from the crown or temples and spreading to the top and back of the head.
These changes in appearance, along with overweight, are challenging for women and girls with PCOS to accept. Consequently, they often experience symptoms of anxiety and depressive disorders ranging from moderate to severe.
Classification and Stages of Polycystic Ovary Syndrome
The main criteria for polycystic ovary syndrome (PCOS) include the absence of ovulation or infrequent ovulation, hyperandrogenism, and polycystic ovarian changes. Based on these criteria, PCOS is classified into the following types:
- Classic type โ all three criteria are present (occurs in 46% of cases)
- Ovulatory type โ ovulation is preserved, but there is clinical or laboratory hyperandrogenism with signs of polycystic ovaries on ultrasound (occurs in 23% of cases)
- Non-androgenic type โ no signs of hyperandrogenism are observed, but ovulation is absent, and there are ultrasound characteristics of polycystic ovaries (occurs in 18% of cases)
- Anovulatory type โ ovulation is absent, and there are signs of hyperandrogenism (occurs least frequently, in 13% of cases)
Depending on the predominant complaints and associated approaches to treatment, three types of PCOS are distinguished:
- Metabolic type, where metabolic disorders predominate (type 2 diabetes, overweight, cholesterol metabolism disorders)
- Hyperandrogenic type, where cosmetic problems associated with excess male sex hormones are predominant (acne, increased hair growth, etc.)
- Reproductive type, where the main complaints are difficulties with conception and carrying a child
Complications of polycystic ovary syndrome include:
- Metabolic syndrome โ a correctable disorder combining obesity with two or more criteria: blood glucose elevation โฅ 5.6 mmol/L or presence of type 2 diabetes, elevated blood pressure (โฅ 130/85 mmHg) or hypertension, blood triglyceride level โฅ 1.70 mmol/L, low-density lipoprotein cholesterol level < 1.3 mmol/L, or treatment with lipid-lowering drugs.
- Gestational diabetes โ diabetes occurring during pregnancy.
- Fatty liver hepatosis โ excessive accumulation of fat in the liver in individuals who do not abuse alcohol, associated with insulin resistance.
- Hypertensive disease โ persistent elevation of blood pressure.
- Obstructive sleep apnea syndrome โ collapse of the airways with cessation or reduction of breathing during sleep, leading to various metabolic and vascular disorders, manifested by snoring, daytime sleepiness, fatigue, mood disorders.
- Cardiovascular diseases: arteriosclerosis โ deposition of cholesterol and other lipids in artery walls; ischemic heart disease โ partial or complete blockage of arteries supplying the heart; myocardial infarction โ necrosis of heart muscle due to acute blood flow disruption; stroke โ acute disruption of cerebral blood flow, and more.
- Increased blood clotting with the formation of thrombi, which can occlude the lumen of vessels in various organs.
- Oncological burden.
- Endometrial hyperplasia โ proliferation of the inner layer of the uterus. Women with polycystic ovaries have an increased risk of developing endometrial cancer (2-6 times higher), which often occurs before menopause.
- Depression, characterized by a decrease in mood, self-esteem, and ability to experience pleasure.
The main cause of most of these complications is insulin resistance, which occurs in 95% of women with obesity or overweight and 75% of women with normal weight in the case of PCOS. It underlies the development of prediabetes, type 2 diabetes, obesity, hypertension, and hypercholesterolemia, which, in turn, lead to the development of cardiovascular diseases. Thus, with insulin resistance, half of patients may eventually develop prediabetes, and a third may develop type 2 diabetes. Itโs noted that insulin resistance in PCOS can indeed be a minor triggering mechanism for the development of Alzheimerโs disease or age-related dementia.
Diagnosis of Polycystic Ovary Syndrome
- Confirmation of ovulatory dysfunction โ the failure of the dominant follicle to mature (anovulation) or its irregular maturation (oligo-ovulation).
Primary methods for determining ovulation or its absence:
- Ultrasonographic folliculometry โ the most accurate method. In cases of irregular menstrual cycles, pelvic ultrasound is performed starting from day 7-9 of the cycle, several times with a 2-3 day interval to monitor the growth of the dominant follicle (up to 18-20 mm). The absence of ovulation in two out of three cycles indicates dysfunction.
- Over-the-counter ovulation tests โ detect the peak of luteinizing hormone surge in urine.
Confirming ovulation involves assessing progesterone levels in the mid-luteal (second) phase of the menstrual cycle (usually corresponding to days 20-24 from the onset of menstruation). A progesterone level below 3-4 ng/mL indicates anovulation, meaning ovulation did not occur.

- Evaluation of clinical manifestations of hyperandrogenism โ excess male sex hormones.
The degree of hirsutism is measured using the Ferriman-Gallwey scale. Each of the nine body areas is assessed on a scale of 0-4 points. A total score โฅ 4-6 indicates hirsutism.
The Ludwig scale is recommended for assessing alopecia associated with excess androgens, categorizing it into three stages: I โ noticeable thinning of hair on the crown, II โ pronounced hair loss on the crown, III โ complete baldness in the crown area.
Assessment of the severity of alopecia, as well as acne, is not conducted during adolescence as they are common issues during this period. - Diagnosis of metabolic syndrome:
- Measurement of BMI or waist circumference.
- Measurement of blood pressure.
- Analysis of fasting plasma glucose, oral glucose tolerance test, glycated hemoglobin (HbA1c) โ these parameters are recommended for assessment in all women already diagnosed with polycystic ovaries, and then once every 1-3 years depending on other risk factors for type 2 diabetes.
- Evaluation of lipid profile parameters โ blood cholesterol, triglycerides, low-density lipoproteins, and high-density lipoproteins.

- Other laboratory abnormalities encountered in PCOS (not diagnostic criteria but indicative of the condition):
- LH/FSH ratio > 2.5 โ occurs in over 60% of cases (tested on days 2-5 of the menstrual cycle).
- Elevated 17-OH progesterone levels above 7.5 nmol/L โ seen in over 50% of cases (tested on days 2-5 of the menstrual cycle).
- Decreased SHBG levels โ in 50% of cases (tested on days 2-5 of the menstrual cycle).
- Fasting insulin levels > 13 mU/L โ in over 30% of cases.
- Elevated total cholesterol and LDL cholesterol โ in over 30% of cases.
- Elevated prolactin levels โ present in 10-30% of patients.
- AMH levels > 4.5 ng/mL.
- Increased HOMA-IR index โ evaluated based on fasting plasma glucose and insulin levels. Although insulin resistance is recognized as a key characteristic of PCOS, specialists currently do not recommend assessing this index in routine clinical practice.
- Endometrial biopsy is indicated for women with acyclic bleeding.
Treatment of Polycystic Ovary Syndrome (PCOS)
The treatment of PCOS is individualized for each case and depends on factors such as age, symptoms, reproductive plans, and the risk of developing cardiovascular diseases.
Overall, the treatment of polycystic ovaries is comprehensive and includes:
- Weight reduction and correction of metabolic disorders:
- Lifestyle modifications: Quitting smoking, normalizing sleep patterns.
- For individuals with elevated BMI: Reducing daily calorie intake to 1200-1500 kcal/day. While the advantage of a specific diet is not yet proven, lifestyle changes are essential.
- Recommendations for physical activity: Adolescents are advised to engage in intense physical activity for at least 60 minutes per day, while women aged 18-64 should aim for at least 150 minutes per week (such as walking, cycling, household chores, sports activities, etc.). Strength training exercises for major muscle groups should be performed at least two days per week. Aim for a daily step count of at least 10,000 steps, including daily activities and 30 minutes of intense physical activity. Using a fitness tracker can be helpful.
- Obesity correction: If weight loss is less than 5% over three months despite lifestyle changes, pharmacotherapy for obesity is considered. Current medications include orlistat (blocks fat absorption in the intestines), sibutramine (acts on the central nervous system to increase satiety and energy expenditure), and liraglutide (subcutaneously administered, improves lipid profiles and moderately reduces elevated blood pressure without excessive risk of hypoglycemia). Liraglutide also regulates appetite and food intake naturally, preventing cardiovascular diseases.
- Surgical interventions for weight reduction: Bariatric surgery, involving gastric and/or intestinal modifications, is considered the most effective treatment for obesity.
- Medications:
- Metformin, a glucose-lowering agent, may be prescribed to adolescents with PCOS, adult women with BMI โฅ 25 kg/m2, and patients at high risk of developing prediabetes and type 2 diabetes.
Itโs important to note that treatment of PCOS is multifaceted and may also include addressing infertility, treating skin manifestations of hyperandrogenism (such as hirsutism and alopecia), restoring and normalizing menstrual cycles, and improving psychological well-being. The choice of treatment approach should be discussed with a healthcare provider based on individual needs and considerations.
Treatment of Infertility in PCOS:
Medications for ovulation induction:
- Letrozole: Inhibits the conversion of androgens to estrogens, leading to decreased estrogen levels and compensatory increase in FSH, promoting the development and maturation of the dominant follicle.
- Clomiphene citrate: Stimulates the production of FSH and LH, inducing the maturation of the dominant follicle.
- Metformin: Increases tissue sensitivity to insulin, reducing insulin resistance, a key factor in PCOS development. It can be used alone for ovulation induction in patients with polycystic ovaries, obesity, or normal weight, or in combination with clomiphene citrate if the latter is not sufficiently effective.
- Gonadotropins: Hormone preparations that mimic the natural peaks of LH and FSH, necessary for the final maturation of follicles and ovulation.
Assisted reproductive technologies (ART) if medications are ineffective:
- In vitro fertilization (IVF): Involves superovulation, puncture of follicles to retrieve eggs, fertilization of eggs in the laboratory, and transfer of embryos into the uterus.
- IVF with intracytoplasmic sperm injection (ICSI): Used when there are sperm-related issues. A single sperm is injected into each egg, and the fertilized eggs are transferred to the uterus.
Surgical interventions:
- Laparoscopic ovarian drilling: Used if medications fail. It involves making small holes in the ovaries to improve ovulation by reducing androgen levels, AMH levels, and improving ovarian blood supply.

Preparation for ovulation induction in ART programs:
- Progesterone supplementation: Used to increase the chances of pregnancy before ovulation induction in IVF programs.
In conclusion, the treatment of infertility in PCOS is tailored to each individual and may involve medications for ovulation induction, assisted reproductive technologies, surgical interventions, and progesterone supplementation in ART programs. Close monitoring and hormonal control are essential to prevent complications such as ovarian hyperstimulation syndrome and multiple pregnancies.
Treatment of hirsutism and alopecia in polycystic ovary syndrome:
Oral Contraceptives (COCs):
- Combined oral contraceptives containing minimal doses of ethinyl estradiol or natural estrogens are recommended.
- Contraindications and limitations, including age, smoking, venous disorders, metabolic pathologies, cardiovascular diseases, and blood clotting mutations, are assessed.
Antiandrogens:
- Spirolactone, cyproterone acetate, finasteride, and flutamide are prescribed alongside COCs if hirsutism symptoms persist after 6-12 months of treatment.
- Antiandrogens are also used for treating androgenic alopecia in PCOS patients, particularly in cases of intolerance to COCs or contraindications.
Inositol:
- Literature discusses the effectiveness of inositol in PCOS treatment, in any form.
Restoration and normalization of menstrual cycle:
- Progestins are used to restore menstrual regularity in PCOS patients not requiring contraception or planning pregnancy. Progestin medications like dydrogesterone, progesterone, and crinone gel are used in the second phase of the cycle.
Improvement of psychological state:
- Psychological therapy, dermatocosmetological treatment of acne under dermatologist supervision, and if necessary, antidepressants for depressive disorders or anxiolytics for anxiety and fear are recommended. The medication with minimal impact on body weight should be chosen.
Here is the list of references:
- Teede H. J., Misso M. L., Costello M. F., Dokras A., et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome // Fertil Steril. โ 2018; 89 (3): 251-268.
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome // Fertil Steril. โ 2004; 81 (1): 19-25.
- Azziz R., Carmina E., Chen Z., Dunaif A., et al. Polycystic ovary syndrome // Nat Rev Dis Primers. โ 2016; 2: 16057.