List of Abbreviations
BP – blood pressure;
ACTH – adrenocorticotropic hormone;
ART – assisted reproductive technologies;
DHEAS – dehydroepiandrosterone sulfate;
BMI – body mass index;
IR – insulin resistance;
FAI – free androgen index;
COC – combined hormonal contraceptives (ATC Progestogens and estrogens, fixed combinations);
LH – luteinizing hormone;
ICD-10 – International Classification of Diseases 10th Revision;
MRI – magnetic resonance imaging;
ncCAH – non-classical congenital adrenal hyperplasia;
IGT – impaired glucose tolerance;
WC – waist circumference;
OGTT – oral glucose tolerance test (Performing a glucose tolerance test);
PCO – polycystic ovaries;
DM – diabetes mellitus;
OHSS – ovarian hyperstimulation syndrome;
OSA – obstructive sleep apnea;
PCOS – polycystic ovary syndrome;
CVD – cardiovascular diseases;
SHBG – sex hormone-binding globulin;
TG – triglycerides;
TSH – thyroid-stimulating hormone;
ultrasound – ultrasound examination;
FSH – follicle-stimulating hormone;
hCG – human chorionic gonadotropin;
Chol – cholesterol;
LDL-C – low-density lipoprotein cholesterol;
HDL-C – high-density lipoprotein cholesterol;
CPA/COC – cyproterone / combined hormonal contraceptives (COC (ATC – progestogens and estrogens, fixed combinations);
EH – endometrial hyperplasia;
EA – endometrial adenocarcinoma;
ASRM – American Society for Reproductive Medicine;
ESHRE – European Society of Human Reproduction and Embryology;
HOMA – Homeostasis model assessment
Terms and Definitions
Anovulation (from the Latin "an" – absence, and "ovulatio" – ovulation) – a condition during which the egg does not mature and is not released from the follicle. It can occur with both regular and irregular menstrual cycles.
Hyperandrogenism – a condition associated with excessive androgen secretion and/or their enhanced effect on the body, which in women most commonly manifests as virilization (appearance of male traits) and androgen-dependent dermopathy (acne, hirsutism, alopecia).
Hirsutism – excessive growth of terminal hair in women following a male pattern. Terminal hairs are dark, coarse, and long, unlike vellus hairs, which are weakly pigmented, soft, and short.
Hypertrichosis – a condition manifested by excessive hair growth that is uncharacteristic of a given skin area and does not correspond to sex and/or age.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Polycystic ovary syndrome (PCOS) – a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman's life from menarche to the transition to menopause, the clinical presentation, diagnosis, and treatment tactics of the disease vary. PCOS has a complex of reproductive, metabolic, and psychological features [1].
PCOS in adolescents1 is diagnosed in the presence of clinical and/or biochemical hyperandrogenism and oligo-amenorrhea since menarche [143].
1 In these clinical guidelines, differences in indicator assessments and management tactics in children and adolescents are described separately.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
PCOS is one of the most common endocrine disorders in women of reproductive age. PCOS is a risk factor for infertility, androgen-dependent dermopathy (acne, hirsutism, alopecia), carbohydrate metabolism disorders (IGT, type 2 diabetes mellitus), dyslipidemia, cardiovascular pathology, endometrial hyperplastic processes, psychological status disorders (e.g., depression, anxiety disorders, mood disorders), and oncological diseases. The overall risk of endometrial, ovarian, and breast cancer is increased in PCOS, which is largely facilitated by the presence of overweight or obesity in 40-85% of women [2-4, 98-100]. Despite numerous studies, it has not yet been possible to formulate a unified concept of the pathogenesis and etiology of PCOS. In the pathogenesis of the disease, disturbances in four different divisions of the neuroendocrine system can be conventionally distinguished, each of which may claim a starting role. These are disorders at the level of the hypothalamic-pituitary system, ovaries, adrenal glands, and peripheral insulin-sensitive tissues [141-142]. In adolescents with PCOS, metabolic syndrome occurs in 10.8-33.3% of cases, which is 3-5 times more frequent compared to an age- and body mass index-matched group of healthy girls.
1.3 Epidemiology of the Disease or Condition
In the general population of women of reproductive age, the prevalence of the syndrome ranges from 8 to 21%. The prevalence rates of PCOS depend on the characteristics of the population sample and the diagnostic criteria used [5].
1.4 Features of Coding the Disease or Condition
Ovarian dysfunction (E28):
E28.2 – Polycystic ovarian syndrome.
1.5 Classification of the disease or condition
The European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) (Rotterdam, 2003) [6, 7] identified the main criteria for PCOS: oligo-anovulation, hyperandrogenism (clinical or biochemical), and polycystic ovarian morphology according to ultrasound examination (US). According to ASRM/ESHRE (2003) and the International PCOS Network (2023), the presence of any 2 out of 3 main criteria determines the presence of a specific type (phenotype) of PCOS [1, 5, 7] (Table 1).
Table 1. Main types (phenotypes) of PCOS
Anovulation | Hyperandrogenism (clinical and/or biochemical) | Polycystic ovarian structure according to ultrasound | |
Type (phenotype) A ("classic") | + | + | + |
Type (phenotype) B ("anovulatory") | + | + | |
Type (phenotype) C ("ovulatory") | + | + | |
Type (phenotype) D ("non-androgenic") | + | + |
1.6 Clinical presentation of the disease or condition
See section 2.1 "Complaints and anamnesis"
2. Diagnostics, medical indications and contraindications for diagnostic methods
Diagnosis of PCOS is carried out on the basis of:
1) Clinical and anamestic data – oligo-amenorrhea;
2) Physical examination – manifestations of clinical hyperandrogenism (hirsutism);
3) Laboratory examination – oligo-anovulation, biochemical hyperandrogenism;
4) Instrumental examination – polycystic morphology of the ovaries according to comprehensive pelvic ultrasound (transvaginal and transabdominal).
Diagnostic approaches differ in adolescents and women of reproductive age. In adolescents, PCOS is diagnosed in the presence of clinical and/or biochemical hyperandrogenism and oligo-amenorrhea since menarche, while ultrasound criteria are practically not used.
Before starting the examination, it is necessary to obtain informed voluntary consent from the parent (other legal representative) of a patient under 15 years of age (a patient with drug addiction – at the age of 16, or a patient recognized in the manner prescribed by law as legally incompetent at the age from menarche to 17 years inclusive, if such a girl due to her condition is unable to give consent to medical intervention) in the manner and form approved by the order of the Russian Ministry of Health dated November 12, 2021, No. 1051n "On approval of the procedure for giving informed voluntary consent to medical intervention and refusal of medical intervention in relation to certain types of medical interventions, forms of informed voluntary consent to medical intervention and forms of refusal of medical intervention."
2.1 Complaints and Anamnesis
Patients with PCOS complain of:
Menstrual irregularities
Signs of androgenization (acne, excessive body and facial hair growth, alopecia)
Infertility
Overweight or obesity, weight gain
When taking a history in patients with PCOS, it is recommended to focus on whether first-degree relatives have PCOS or clinical manifestations of the syndrome without a formal diagnosis (oligo/amenorrhea, infertility), as well as on concomitant gynecological and extragenital conditions associated with PCOS, such as abnormal uterine bleeding (including juvenile bleeding) and a history of diagnosed endometrial hyperplasia, diabetes mellitus, arterial hypertension, obstructive sleep apnea, and others [1, 2, 8, 23, 30].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
2.2 Physical Examination
In the presence of clinical hyperandrogenism (acne, excessive body and facial hair growth, scalp hair loss), specific evaluation methods should be performed.
It is recommended to calculate the hirsutism score in women complaining of excessive facial and body hair growth to assess the severity of hirsutism using the modified Ferriman-Gallwey scale (Appendix G1, Fig. 1) [5, 8, 9, 10, 11].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: The prevalence of hirsutism in the classic PCOS phenotype reaches 75%. According to recent recommendations, a modified Ferriman-Gallwey score ≥4–6 generally indicates hirsutism, although there are racial specificities in the assessment of hirsutism [1]. In some Caucasian and Black women, a score ≥8 on this scale is pathognomonic. For Southeast Asian women, a diagnostically significant increase in this scale score is ≥3 [12]. More pronounced hirsutism is characteristic of women from the Middle East, Latin America, and the Mediterranean region [1]. However, the degree of hirsutism in PCOS does not always correlate with the severity of androgen excess. Severe hirsutism may be observed with only a slight increase in serum androgen levels, and a significant elevation in parameters is not always accompanied by hirsutism. This discrepancy between hormone levels and the degree of hirsutism reflects varying individual target tissue sensitivity to androgens.
It is recommended to assess the stage of sexual development using the Tanner scale in adolescents with PCOS, with scoring for breast development (B1–5), pubic hair growth (P1–5), and the presence and rhythm pattern of menstrual cycles (Me0–3) [143, 145].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: The Ferriman-Gallwey scoring system is not adapted for children; therefore, it is not used by the Androgen Excess and PCOS Society (AES) for assessing hirsutism in adolescents [143].
An appointment (examination, consultation) with a dermatologist is recommended in the presence of complaints of acne and hair loss to identify the cause of these pathological conditions [10, 13].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comments: There are no validated rating scales for determining the severity of acne eruptions. The presence of acne and alopecia are not reliable criteria for hyperandrogenism. In adolescents, only severe acne is considered a clinical sign of hyperandrogenism.
It is recommended to perform a physical examination evaluating for the presence of acanthosis nigricans in PCOS to rule out clinical signs of insulin resistance [13, 14, 15].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: Clinical markers of IR in patients with PCOS include acanthosis nigricans (papillary-pigmentary dystrophy of the skin manifesting as localized areas of brown hyperpigmentation in skin folds, most commonly the neck, axillae, and groin regions, which are histologically characterized by hyperkeratosis and papillomatosis).
It is recommended to measure height and body weight and calculate BMI in all patients with suspected PCOS to diagnose overweight or obesity (Appendix A3.1) [1, 7, 17, 18, 19, 20, 109].
Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)
Comments: BMI is calculated using the formula: BMI (kg/m2) = body weight (kg) / height2 (m2). Elevated BMI is more common in PCOS than in the general population, which increases the risk of type 2 diabetes by 4-fold in this population [90].
Obesity in PCOS is:
— an additional risk factor for cardiovascular diseases;
— a risk factor for endometrial cancer (which occurs 2–6 times more frequently compared to women without PCOS);
— an aggravating risk factor for depressive and anxiety disorders;
— a factor affecting birth rates, response to reproductive function restoration, and pregnancy outcomes.
It is recommended that all patients with suspected PCOS undergo waist circumference (WC) measurement (A02.03.007.004) to diagnose abdominal (visceral) obesity (Appendix A3.1) [17, 18, 19, 20].
GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)
Comments: An indicator of abdominal (visceral or male-type) obesity (which is associated with higher risks of carbohydrate metabolism disorders and cardiovascular diseases) in women is a waist circumference >80 cm. In Japan, values of 85 cm for men and 90 cm for women are used [101]. Women with PCOS are more likely to have abdominal obesity, which is associated with metabolic diseases. Abdominal obesity is directly linked to insulin resistance (IR). Waist circumference measurement (A02.03.007.004) is an informative and simple anthropometric method for detecting metabolic disorders, as this parameter directly correlates with the amount of abdominal fat.
2.3 Laboratory Diagnostics
It is recommended that all women with suspected PCOS undergo blood testing for total testosterone and sex hormone-binding globulin (SHBG) using enzyme-linked immunosorbent assay (ELISA) with calculation of the free androgen index to assess the presence of biochemical hyperandrogenism [1, 2, 4, 7, 21-23, 120].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: The free androgen index (FAI) is an indicator of the ratio of total testosterone to sex hormone-binding globulin (SHBG). To calculate the FAI, the formula is used: FAI = total testosterone (nmol/L) / SHBG (nmol/L) × 100. It should be taken into account that in most adolescents, androgen levels do not reach the "adult" range until at least 12–15 years of age, and the assessment of biochemical hyperandrogenism is non-objective [127].
To assess the presence of biochemical hyperandrogenism in patients with suspected PCOS, it is recommended to perform blood tests for total testosterone and free testosterone levels using liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry [1, 2, 4, 7, 21-23, 119].
For adult patients, Level of Recommendation B (Level of Evidence – 3)
For adolescents, Level of Recommendation C (Level of Evidence – 5)
Comments: When interpreting testosterone levels, it is necessary to be guided by the age-specific reference intervals used by laboratories [127, 147].
It is recommended that all patients with PCOS undergo blood testing for dehydroepiandrosterone sulfate (DHEA-S) and androstenedione when total and free testosterone levels are not elevated, although these markers provide limited additional information in the diagnosis of PCOS [1, 2, 4, 7, 21-23].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comment: Hyperandrogenemia is indicated by an elevation in at least any one of the determined androgens or the free androgen index.
It is recommended to test blood anti-Müllerian hormone (AMH) levels in adult women with suspected PCOS as one of the diagnostic criteria for PCOS [127].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: An elevated AMH level is not a mandatory criterion for diagnosing PCOS in adults and should not be used as the sole diagnostic criterion for PCOS. Serum AMH should be used strictly in accordance with the diagnostic algorithm, keeping in mind that in patients with irregular menstrual cycles and hyperandrogenism, AMH levels are not required for diagnosing PCOS. Serum AMH levels should not be assessed in adolescents. AMH levels can be influenced by a woman's age, body mass index, intake of hormonal drugs (e.g., hormonal contraception), and surgical treatment of ovarian diseases [127].
Assessment of biochemical hyperandrogenism is not recommended in women taking combined hormonal contraceptives (according to the Anatomical Therapeutic Chemical (ATC) classification – progestogens and estrogens, fixed combinations) or other hormone-containing drugs that affect testosterone levels due to the potential for false results (according to ATC – Spironolactone**, Antiandrogens) [1, 2, 4, 7, 21-23].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: If evaluation of serum androgen levels is necessary, hormonal medications must be discontinued for 3 months. During the discontinuation period of CHCs (according to ATC – progestogens and estrogens, fixed combinations), women not planning pregnancy should be offered non-hormonal methods of contraception.
It is recommended to assess glycemic status by performing a 2-hour 75 g oral glucose tolerance test (OGTT) (INN: dextrose, powder for oral solution) or by testing blood glycated hemoglobin levels in patients with PCOS without diabetes mellitus, regardless of BMI and other risk factors, to detect carbohydrate metabolism disorders, subsequently every 1–3 years taking into account individual risk factors for carbohydrate metabolism disorders [1, 2, 4, 118, 127-130].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: The oral glucose tolerance test is optimal for screening and diagnosing impaired glucose tolerance and type 2 diabetes mellitus in women with PCOS and has advantages over fasting blood glucose and glycated hemoglobin testing [148].
Carbohydrate metabolism disorders develop more frequently in women of reproductive age with PCOS than in the general population (5 times higher in Asia, 4 times higher in the USA, and 3 times higher in Europe), regardless of obesity, though exacerbated by its presence. The assessment of indications for OGTT in patients with PCOS should be performed at the initial consultation, during pre-conception preparation, and during pregnancy between the 24th and 28th weeks (in the absence of pregestational diabetes mellitus) [1, 2, 4, 7, 21-23, 127-130].
It is not recommended to routinely test blood plasma insulin levels and insulin resistance (IR) indices in patients with suspected or verified PCOS due to their limited clinical significance [1, 24-30, 35].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: In some cases, the HOMA index value can be used to assess IR (fasting glucose level (mmol/L) × fasting insulin level (mIU/L) / 22.5; the normal value for women of reproductive age is – less than 2.7). The HOMA index is not considered a reliable marker of IR in adolescents [127].
It is recommended to study the serum lipid profile (blood cholesterol test, blood high-density lipoprotein cholesterol test, low-density lipoprotein cholesterol test, blood triglyceride test) to diagnose dyslipidemia in all patients with PCOS [1, 6].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: The most frequent form of lipid metabolism disorders in patients with PCOS is dyslipidemia (elevated total cholesterol, triglycerides, LDL cholesterol, and/or decreased HDL cholesterol), which occurs more frequently in obese patients. The lipid panel is evaluated once a year in cases of various dyslipidemias and/or overweight [1, 6].
2.4 Instrumental Diagnostics
It is recommended to perform a comprehensive pelvic ultrasound (transvaginal and transabdominal) in patients with PCOS or suspected PCOS to verify the diagnosis [1, 7, 38-41, 116].
For adult patients, Strength of Recommendation A (Level of Evidence – 2)
For adolescents, Level of Recommendation C (Level of Evidence – 5)
Comments: The number of ovarian follicles per cross-section and ovarian volume should be considered ultrasound markers of polycystic ovaries in adults [127].
Ultrasonographic criteria for polycystic ovaries:
— when using transvaginal transducers ≥8 MHz – the presence of ≥20 follicles measuring 2–9 mm in diameter in either ovary and/or an increased volume of either ovary ≥10 cm3 (in the absence of a corpus luteum, cysts, or dominant follicles),
— when using transvaginal transducers with lower resolution characteristics or during transabdominal examination – an increased volume of either ovary ≥10 cm3 (in the absence of a corpus luteum, cysts, or dominant follicles).
In the presence of a corpus luteum, cysts, or dominant follicles, the ultrasound is repeated after spontaneous or induced menstruation.
It is not recommended to use ultrasound features of polycystic ovaries in adolescents with suspected PCOS for 8 years after menarche as a diagnostic criterion due to the high frequency of multifollicular ovarian morphology at this age [1, 38, 39, 102].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to use the transvaginal approach for comprehensive pelvic ultrasound (transvaginal and transabdominal) or transvaginal ultrasound of the uterus and appendages in women with a preserved menstrual cycle during the follicular phase, and in cases of oligomenorrhea/amenorrhea – either independently of menstruation or on cycle days 3–5 following progestogen-induced withdrawal bleeding [1, 7, 38].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: These criteria should not be used in women receiving combined hormonal contraceptives (CHCs) (ATC: Progestogens and estrogens, fixed combinations).
2.5 Other Procedures
Diagnosis of irregular menstrual cycle (oligo-amenorrhea)
It is recommended to use the following criteria for diagnosing an irregular menstrual cycle in women of reproductive age:
— cycle duration of more than 35 days or fewer than 8 menstrual cycles per year in women;
— cycle duration of less than 21 days [144].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to use the following criteria for an irregular cycle in adolescents [102, 144]:
— duration >90 days for any cycle in the first year after menarche, <21 or >45 days in the period from 1 to 3 years after menarche,
— primary amenorrhea by age 15 or more than 3 years after thelarche, <21 or >35 days, or <8 cycles per year in the period starting 3 years after menarche.
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Using data from large-scale epidemiological studies, FIGO previously determined that for individuals aged 18–45 years, using the 5th–95th percentiles from large population studies, the normal menstrual frequency is 24–38 days. These studies did not assess the presence of ovulation [145, 146].
For adolescents who have characteristic signs of PCOS but do not meet the diagnostic criteria, an "increased risk" of developing PCOS may be considered, and re-evaluation of parameters can be scheduled in 1 year [1].
It is recommended in women of reproductive age with a regular menstrual cycle to test blood progesterone levels in the predicted luteal phase to verify ovulatory dysfunction [1, 7, 38].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: The test is performed 6–8 days after expected ovulation. A progesterone level of less than 3 ng/mL in the mid-luteal phase indicates anovulation; a level below 10 ng/mL or the sum of measurements across 3 consecutive cycles of less than 30 ng/mL may indicate a deficient luteal phase of the menstrual cycle.
With regular menstrual cycles, evaluation of ovarian ovulatory function is possible via comprehensive pelvic ultrasound (transvaginal and transabdominal) on days 20–24 of the menstrual cycle.
Cardiovascular disease (CVD) risk assessment in women with PCOS
It is recommended to measure blood pressure on peripheral arteries in women with PCOS annually, as well as when planning pregnancy in a natural cycle, when planning an ART protocol, or in the presence of frequent complaints due to the increased risk of cardiovascular disease (CVD) [1, 7, 46-51, 113, 127, 137-139].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to measure waist circumference and calculate BMI at each visit for all women with PCOS due to the increased CVD risk [1, 7, 46-51, 113].
GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)
It is recommended to perform a lipid profile evaluation (biochemical blood test for lipid metabolism disorders) and assess CVD risk in patients with PCOS at the initial appointment (examination, consultation) with an obstetrician-gynecologist due to the increased risk of CVD, with subsequent frequency of testing depending on the identified pathology [1, 7, 46-51, 113].
GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)
Comments: Women with PCOS are classified in the risk group if they have at least one of the following factors: obesity (especially abdominal), smoking, hypertension, physical inactivity, dyslipidemia, subclinical atherosclerosis, impaired glucose tolerance, family history of early CVD (under 55 years in male relatives, under 65 years in female relatives).
It is recommended for women with PCOS who are overweight or obese to have a consultation with a dietician and a consultation/testing with a clinical psychologist to adjust dietary intake, rule out or identify eating disorders, and address anxiety and depressive disorders [127].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
Treatment goals: normalization of body weight and correction of metabolic disorders, elimination of symptoms of androgen-dependent dermatopathy, regulation of the menstrual cycle for the prevention of endometrial hyperplasia, restoration of ovulatory menstrual cycles and fertility, and prevention of late complications of PCOS.
Patient management is carried out taking into account main complaints, reproductive plans, presence of cardiovascular disease risk, and other factors.
CHCs, #metformin**, #letrozole, and other medications for PCOS are used off-label, but numerous scientific studies confirm their efficacy. Physicians must inform patients and discuss the efficacy, potential side effects, and consequences of therapy to develop a personalized management strategy. Administration routes and doses are presented below.
3.1 Conservative Treatment
It is recommended that patients with PCOS use lifestyle modifications, including exercise and a rational, balanced diet, to achieve and maintain a normal body weight, general health, and quality of life throughout their lifespan [56-58].
GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)
Comments: Achievable goals, such as a 5-10% weight loss over 6 months in overweight patients, lead to significant clinical improvements. Weight loss through lifestyle modifications in patients with PCOS helps normalize menstrual function and improves several metabolic parameters (predominantly carbohydrate metabolism), although the response is individual. There is insufficient evidence to recommend any specific diet for PCOS. It is important to tailor dietary changes to the patient's eating habits using a flexible and individualized approach to calorie reduction while avoiding overly restrictive and unbalanced diets. Physical activity in adults aged 18-64 should include at least 150 minutes per week of moderate-intensity aerobic physical activity, or 75 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of both, including muscle-strengthening exercises on 2 non-consecutive days per week.
It is recommended to prescribe combined hormonal contraceptives (CHCs; ATC: progestogens and estrogens, fixed combinations) as first-line therapy for patients with PCOS presenting with menstrual cycle irregularities and clinical manifestations of hyperandrogenism (hirsutism and acne) [1, 59-64, 127, 140].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: Women with PCOS who are not seeking pregnancy are prescribed CHCs containing the lowest effective dose of ethinylestradiol (20-30 mcg) or natural estrogens, taking into account the WHO Medical Eligibility Criteria for Contraceptive Use [65] and National Medical Eligibility Criteria for Contraceptive Methods [140]. CHCs can be considered as therapy in adolescents at risk for PCOS or with a diagnosis of "developing PCOS" presenting with hirsutism and irregular menstrual cycles. The progestogen component of CHCs suppresses LH secretion, leading to a decrease in ovarian androgen production; the estrogen component helps increase SHBG levels and decrease free circulating testosterone. Any CHC with any estrogen dose can be used for treatment in adult women with PCOS; however, preparations containing 35 mcg of ethinylestradiol and cyproterone (which are more effective for hirsutism and biochemical hyperandrogenism compared to standard CHCs) should not be considered as first-line therapy for PCOS due to side effects, including the risk of venous thromboembolism [1]. A preparation containing a progestogen with no residual androgenic activity should be chosen. It is also necessary to consider associated conditions such as overweight and obesity, hyperlipidemia, and arterial hypertension. Research results show that hyperhomocysteinemia, a risk factor for cardiovascular disease, is 3 times more common in patients with PCOS. In most cases, elevated homocysteine levels result from folate deficiency in the body, so patients with PCOS may be prescribed CHCs containing folates [92-96, 103-107, 140-141].
It is recommended to use a combination of CHCs and non-steroidal antiandrogens in the treatment of hirsutism if CHCs fail to provide a significant clinical effect after 6 months [59, 111].
GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)
It is recommended to use anti-androgens as monotherapy for hirsutism only if there are contraindications to CHCs or in case of CHC intolerance [66, 111].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: Reliable contraception is required when prescribing antiandrogens.
The following antiandrogen regimens are recommended for the treatment of hirsutism [1]:
— #Spironolactone** (50-100 mg daily) (lower risk of side effects) for the treatment of acne [1, 2, 122].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
— #Finasteride (2.5-5 mg daily for 6-12 months) or #flutamide (250-500 mg daily [250 mg 1-2 times daily] for 6-12 months) are not registered in Russia for the treatment of hirsutism in women, although they may be effective [111]. #Finasteride and #flutamide are hepatotoxic, which should be taken into account when selecting therapy [127].
Leveled of Evidence CLevel of Data Reliability 2Level of evidence C (level of data reliability – 2)
Cyproterone** ≥10 mg daily for the treatment of hirsutism is not recommended due to high risks, including meningioma in patients aged 18 years and older [1].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to prescribe cyclic progestogen therapy (ATC: progestogens) to women with PCOS to regulate the cycle and prevent endometrial hyperplasia and cancer if they are unwilling to use combined oral contraceptives or have contraindications to their use [127].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: According to the 2023 international PCOS guidelines [127], it is a strong recommendation that healthcare providers take into account the fact that women of reproductive age with PCOS have a significantly higher risk of developing endometrial hyperplasia and cancer. Preventive strategies regarding the risks of endometrial hyperplasia and cancer include weight loss, menstrual cycle regulation, and regular progestogen intake. Indications listed in progestogen product information include: menstrual cycle disorders due to ovulation disorders; irregular menstruation; secondary amenorrhea.
It is recommended to use #metformin** as a 2nd-line therapy in patients with PCOS and irregular menstruation who have contraindications to CHCs or are intolerant to them, including those with a normal BMI [59, 66, 68, 127].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: #Metformin** is prescribed at a dose of 500 mg daily, with a gradual weekly increase of 500 mg. The maximum daily dose is 2.5 g for adults and 2 g for adolescents [1, 59, 66, 68, 69].
It is recommended to use #metformin** in addition to lifestyle modifications in women with PCOS and a BMI ≥25 kg/m2 for weight control and improved metabolic outcomes, as well as in adolescents at "risk group" or with an established diagnosis of PCOS [66, 69].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: #Metformin** may have a therapeutic effect in groups of women at high metabolic risk (risk factors for diabetes mellitus, impaired glucose tolerance, or certain high-risk ethnic groups). When prescribing #metformin**, gastrointestinal side effects, which are generally dose-dependent, must be taken into account. Therefore, treatment should be started at a low dose, increasing by 500 mg 1-2 times a week [1]. Extended-release formulations can minimize side effects. It should be remembered that long-term use of #metformin** can lead to vitamin B12 deficiency, so the prescription of this therapy should be discussed with the patient. The woman should be informed about the potential efficacy, risks, and side effects of this treatment.
It is recommended to use #metformin** (MF) in adult women with PCOS and a BMI ≥25 kg/m2 as part of a comprehensive approach to correcting metabolic syndrome (improving tissue insulin sensitivity, preventing carbohydrate metabolism disorders, and correcting dyslipidemia) [127].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: MF monotherapy may be considered in adolescents at risk of developing PCOS or with PCOS to regulate the menstrual cycle.
When prescribing MF, the following must be taken into account:
— MF prescription is effective when combined with active lifestyle modifications;
— Mild gastrointestinal side effects may occur, which are dose-dependent and resolve on their own;
— Initiating therapy with a low dose, increasing by 500 mg 1-2 times a week, and using extended-release formulations (which helps reduce the risk of undesirable side effects);
— Treatment may be accompanied by the development of low vitamin B12 levels, especially in individuals with risk factors for low vitamin B12 (e.g., DM, kg/m
It is recommended to combine CHCs and #metformin** (according to the previously indicated regimen) in women with PCOS and a BMI >30 kg/m2 who are at high risk for carbohydrate metabolism disorders or belong to high-risk ethnic groups, for the correction of metabolic disorders when CHCs and lifestyle modifications fail to achieve the desired goals [127].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to use pharmacotherapy for obesity in patients with PCOS and a BMI ≥30 kg/m2 or BMI ≥27 kg/m2 in the presence of at least one of the following complications: arterial hypertension, dyslipidemia, type 2 diabetes mellitus, or obstructive sleep apnea syndrome, in accordance with the clinical guidelines for "Obesity" [1, 66, 70, 71, 127, 151-152].
GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)
Comments: Behavioral therapy aimed at reducing food intake and increasing physical activity is a mandatory condition of the treatment provided. Pharmacological support may be prescribed, including liraglutide, semaglutide**, orlistat, in addition to lifestyle modification in overweight/obese women with PCOS. The efficacy of medical obesity therapy should be evaluated 3 months after the start of treatment. Weight loss of less than 5% of baseline within 3 months can be considered ineffective. Obesity treatment in women with PCOS should be carried out under the supervision of a specialist – a medical psychologist/psychotherapist, taking into account data on eating disorders. It is mandatory to discuss contraception counseling with a female patient taking pharmacological obesity therapy. For details, see the relevant clinical guidelines.
The use of pharmacotherapy (in combination with lifestyle modification) in obese children and adolescents is prescribed from the age of 12 when measures aimed at forming a healthy lifestyle lasting at least 1 year are ineffective. See clinical guidelines "Obesity in Children".
It is recommended to use bariatric surgery for PCOS and BMI ≥35 kg/m2 or ≥30 kg/m2 in the presence of obesity-related complications [66, 150].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Surgical treatments for morbid obesity (bariatric surgery) in adolescents have become increasingly widespread globally in recent decades. The main advantages of bariatric surgery are rapid weight loss, improvement of metabolic parameters, and quality of life in patients with morbid obesity. According to the clinical guidelines of the Endocrine Society, bariatric surgery is the method of choice for the treatment of complicated morbid obesity in adolescents [149].
It is recommended to use clomifene** in patients with PCOS as first-line therapy for the treatment of anovulatory infertility [73].
GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: The goal of treatment for patients with PCOS is the restoration of ovulatory menstrual cycles. Lifestyle modification, in particular obesity treatment, should precede ovulation induction in PCOS. Before ovulation induction in women with PCOS, other causes of infertility in the couple (tubal-peritoneal, male factors) must be ruled out.
Clomifene** is prescribed for 5 days, starting from days 2–5 of a spontaneous or induced menstrual cycle. The starting dose is usually 50 mg per day, and the maximum daily dose is 150 mg. The ovulation rate reaches 70–80%, and the pregnancy rate reaches 22% per cycle. Treatment with clomifene** is carried out for no more than 6 menstrual cycles. The cumulative live birth rate per 6 cycles of ovulation induction is 50–60% [91]. An elevated free androgen index and BMI, the presence of amenorrhea, and increased ovarian volume are predictors of clomifene** treatment failure [92].
It is recommended as an alternative treatment regimen for anovulatory infertility in patients with PCOS #letrozole [126].
GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)
Comments: According to international clinical guidelines, the first-line drug for the treatment of anovulatory infertility is the non-steroidal aromatase inhibitor – #letrozole [1], however, in Russia this prescription is off-label. Ovulation induction with #letrozole is carried out at a dose of 2.5 mg per day (orally) from days 3 to 7 or 5 to 9 of the menstrual cycle; if ovulation does not occur in the next stimulation cycle, it is possible to increase the dose of #letrozole to 5 mg per day. The maximum dosage of #letrozole in the ovulation induction protocol is 7.5 mg per day [124, 126]. According to randomized controlled trials and meta-analyses, #letrozole is 1.5 times more effective than clomifene** in achieving ovulation, pregnancy, and live birth without increasing the risks of multiple pregnancy or miscarriage [125].
It is recommended to use #metformin** (according to the previously specified regimen) in patients with PCOS and anovulatory infertility, as well as the absence of other infertility factors, as an alternative ovulation induction regimen and to improve ovulatory function, both as monotherapy and in combination with clomifene** (CC) according to the standard regimen of indirect ovulation inducers [73–75].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: To overcome CC resistance, it can be combined with #metformin** to increase the chances of pregnancy (a 1.6-fold increase in ovulation and conception rates, and a 1.2-fold increase in live birth rates). If #metformin** is used for ovulation induction in women with PCOS, obesity (BMI ≥30 kg/m2), anovulatory infertility, and the absence of other infertility factors, CC (according to the standard regimen) can be added to improve ovulatory function and the probability of pregnancy.
It is recommended in patients with PCOS and anovulatory infertility to perform ovulation induction with gonadotropins or laparoscopy with ovarian drilling as a 2nd-line therapy when CC is ineffective or conditions for its use are absent [76, 77, 112].
GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: Gonadotropins can be used in combination with #metformin** (dosing regimen – see above) in women with PCOS, anovulatory infertility, CC resistance, and the absence of other infertility factors to improve ovulatory function, increase the likelihood of pregnancy and live birth rates. The duration of gonadotropin use should not exceed 6 cycles. When performing stimulation with gonadotropins, it is necessary to monitor the ovarian response.
It is recommended for adult patients with PCOS to prescribe inositol as an alternative to #metformin** for irregular menstrual cycles, metabolic syndrome, and obesity [127, 131–136].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Patients should be informed about the limited clinical effect. The specific supplement composition, dose, and duration of therapy are currently not defined [127, 131–136].
3.2 Surgical Treatment
It is recommended to perform laparoscopy (laparoscopic drilling) in women with PCOS and infertility in case of CC resistance, high LH levels, other indications for laparoscopic surgery in patients (endometriosis, tubal-peritoneal infertility factor), and the impossibility of monitoring during the use of gonadotropins [78].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: The efficacy of laparoscopic drilling and the use of gonadotropins are comparable. Monopolar electrocautery and lasers are used with equal efficacy [67, 108]. To achieve an effect in PCOS, 4 ovarian punctures are sufficient; a higher number of punctures is associated with an increased risk of premature ovarian insufficiency. Ovulation induction is required in 50% of patients after laparoscopy. If ovulation is absent 12 weeks after laparoscopy, CC stimulation should be used, and after 6 months of CC use, gonadotropins may be used.
It is not recommended to perform laparoscopic drilling in patients with PCOS for the purpose of solving problems not directly related to infertility, namely: for the correction of irregular menstrual cycles or hyperandrogenism [79].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Specific rehabilitation has not been developed
5. Prevention and Dispensary Observation
Taking into account long-term cardiovascular risks, it is recommended to establish dispensary follow-up (dispensary appointment (examination, consultation) by an obstetrician-gynecologist) for patients with PCOS; adherence to the principles of rational nutrition and dosed physical activity is also necessary [110, 127].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
6. Organization of Medical Care
Indications for hospital admission to a medical organization:
1) Surgical treatment of PCOS
Discharge criteria: clinical recovery
7. Additional Information
Differential diagnosis
The most common nosologies masquerading as PCOS are presented in Appendix A3.2.
It is recommended in patients with suspected PCOS to exclude thyroid diseases, hyperprolactinemia, and the non-classical form of congenital adrenal hyperplasia (NCAH) during differential diagnosis by testing blood thyroid-stimulating hormone (TSH) levels, blood total thyroxine (T4) levels, and blood prolactin levels [1, 7, 38, 42–46].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: The diagnostic criteria for overt hypothyroidism are an increase in blood thyroid-stimulating hormone (TSH) levels above the normal range and a decrease in serum free thyroxine (FT4) levels. A decrease in TSH levels below the lower limit of normal (usually less than 0.1 mIU/L) indicates hyperthyroidism. It is advisable to perform laboratory testing of prolactin levels at least twice.
It is recommended in women with signs of hirsutism, alopecia, acne, menstrual irregularities, infertility, and/or recurrent pregnancy loss to test blood 17-hydroxyprogesterone levels in the early follicular phase in the morning to diagnose NCAH; in case of borderline 17-hydroxyprogesterone values, pathogenic variants of the CYP21A2 gene should also be tested [1, 7, 38, 43, 46, 115].
GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)
Comments: To diagnose the non-classic form, blood sampling for 17-OHP is performed early in the morning in the follicular phase of the cycle (no later than days 5–7); in case of amenorrhea, it is done on any day, strictly outside of pregnancy. Values below 6 nmol/L or below 2 ng/mL are considered normal; below these levels, NCCAH is practically nonexistent. It should be borne in mind that reference ranges provided by various laboratories usually differ and can be significantly lower than the specified "cut-off points" for diagnosing NCCAH. In case of basal 17-OHP values exceeding 30 nmol/L or 10 ng/mL, the diagnosis of CAH is considered confirmed, and no additional diagnostics are required. In case of borderline 17-OHP values (6–30 nmol/L or 2–10 ng/mL — the so-called "gray zone") detected on at least two separate determinations, testing for pathogenic variants of the CYP21A2 gene is advisable.
7.1 ART and PCOS
It is recommended to use assisted reproductive technologies (ART) in women with PCOS and infertility when ovulation induction and laparoscopy are ineffective; in the presence of concomitant pathology (tubal-peritoneal factor of infertility, endometriosis, male factor), or when preimplantation genetic testing is required [76, 82, 121].
GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)
Comments: In female patients with PCOS undergoing ART, the risk of ovarian hyperstimulation is high. The clinical pregnancy rate per treatment cycle in women with PCOS is 35%, which is comparable to that in patients without PCOS.
A GnRH antagonist protocol (ATC – Gonadotropin-releasing hormone analogues) is preferred to reduce the duration of stimulation, the dose of gonadotropins, and the incidence of OHSS.
GnRH agonists (ATC – Gonadotropin-releasing hormone analogues) as a trigger for final oocyte maturation are recommended in patients at elevated risk of OHSS or in the case of deferred embryo transfer [1].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to use #metformin** as adjuvant therapy to prevent ovarian hyperstimulation syndrome in women with PCOS undergoing ART treatment [1, 83–86].
GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)
Comments: #Metformin** can reduce the risk of hyperstimulation, but it does not significantly affect the live birth rate. #Metformin** is prescribed at a daily dose of 1000 to 2500 mg [1, 83–86]. The development of ovarian hyperstimulation syndrome is not characteristic of In Vitro Maturation (IVM), making this method a viable alternative.
7.2 Obstetric aspects of PCOS
It is recommended to perform preconception care in women with PCOS to reduce gestational complications [87, 88].
GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)
Comments: Women with PCOS represent a risk group for adverse pregnancy outcomes: miscarriage, GDM, gestational hypertension and preeclampsia, intrauterine growth restriction, macrosomia, preterm birth, and cesarean section. According to meta-analyses, the incidence of GDM, arterial hypertension, and preeclampsia increases 3- to 4-fold. The risk of complicated pregnancy is higher in women with the "classic" PCOS phenotype. Preconception care should include: smoking cessation, lifestyle modification, and the use of folic acid [87–89, 127].
It is recommended to provide mandatory follow-up for women with PCOS during pregnancy due to the increased risk of gestational diabetes, hypertensive disorders, preeclampsia, and related complications, in particular an increased risk of neonatal morbidity [87–89].
GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)
Criteria for Evaluating the Quality of Medical Care
This section presents the criteria for evaluating the quality of medical care for polycystic ovary syndrome recommended by the Working Group, indicating the level of evidence and the grade of recommendation (Table 2).
Table 2. Criteria for evaluating the quality of medical care in PCOS
№ | Quality criteria | Performance assessment (yes/no) |
Assayed blood total testosterone, blood sex hormone-binding globulin, and calculated the free androgen index | Yes/no | |
Comprehensive pelvic ultrasound was performed (transvaginal and transabdominal) | Yes/no | |
Assessed glycemic status by performing a 2-hour 75 g oral glucose tolerance test or assayed blood glycated hemoglobin in patients with PCOS | Yes/no | |
Measured height and body weight with body mass index calculation, and measured waist circumference (A02.03.007.004) in patients with PCOS | Yes/no | |
Measured peripheral arterial blood pressure in patients with PCOS | Yes/no | |
Prescribed medical therapy for menstrual irregularities, hirsutism, and acne (COCs, nonsteroidal antiandrogens, progestogens (ATC – progestogens) in a cyclic regimen) | Yes/no | |
Provided lifestyle modification recommendations including exercise and a balanced diet for the treatment of obesity and overweight in patients with PCOS | Yes/no | |
Prescribed clomifene** as first-line therapy for the treatment of anovulatory infertility in PCOS | Yes/no | |
Performed ovulation induction with gonadotropins or laparoscopy (laparoscopic ovarian drilling) as second-line therapy when clomifene** is ineffective or conditions for its use are absent | Yes/no |
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Appendix A1. Working Group Composition
Adamyan Leyla Vladimirovna | Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Deputy Director of the V.I. Kulakovskiy National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Honored Scientist of Russia, Head of the Department of Obstetrics, Gynecology and Reproductive Medicine at the Russian University of Medicine, Chief Freelance Gynecologist of the Russian Ministry of Health, member of the Society for Reproductive Medicine and Surgery, Russian Association of Gynecological Endoscopists, Russian Endometriosis Association, Russian Society of Obstetricians and Gynecologists. |
Andreeva Elena Nikolaevna | Doctor of Medical Sciences, Professor, Deputy Director - Director of the Institute of Reproductive Medicine, Head of the Department of Endocrine Gynecology, Professor at the Department of Endocrinology of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Professor at the Department of Obstetrics, Gynecology and Reproductive Medicine of the Russian University of Medicine, President of the International Association of Obstetricians, Gynecologists and Endocrinologists, member of the Russian Association of Gynecological Endoscopists, Russian Endometriosis Association, Russian Society of Obstetricians and Gynecologists, ROSGEM. |
Absatarova Yulia Sergeevna | Candidate of Medical Sciences, Senior Researcher at the Department of Endocrine Gynecology of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, member of the International Association of Obstetricians, Gynecologists and Endocrinologists. |
Grigoryan Olga Rafaelievna | Chief Researcher at the Department of Endocrine Gynecology of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Doctor of Medical Sciences, Professor |
Dedov Ivan Ivanovich | President of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Chief Freelance Endocrinologist of the Russian Ministry of Health, Academician of the Russian Academy of Sciences, member of the Russian Association of Endocrinologists |
Melnichenko Galina Afanasyevna | Deputy Director for Science of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Academician of the Russian Academy of Sciences, member of the Russian Association of Endocrinologists |
Smetnik Antonina Alexandrovna | Candidate of Medical Sciences, Head of the Department of Gynecological Endocrinology at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, President of the Russian Society of Gynecological Endocrinology and Menopause Specialists |
Suturina Larisa Viktorovna | Chief Researcher, Head of the Department of Reproductive Health Protection at the Scientific Centre for Family Health and Human Reproduction Problems, Doctor of Medical Sciences, Professor, member of the Association of Gynecological Endocrinologists of Russia, member of the Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS Society) |
Filippov Oleg Semenovich | Doctor of Medical Sciences, Professor, Honored Doctor of the Russian Federation, Chief Freelance Obstetrician-Gynecologist of the FMBA of Russia, Deputy Director of the Federal Scientific and Clinical Center of Children and Adolescents of the FMBA of Russia, Professor at the Department of Obstetrics, Gynecology and Reproductive Medicine of the Russian University of Medicine |
Sheremetyeva Ekaterina Viktorovna | Leading Researcher at the Department of Endocrinology of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Candidate of Medical Sciences, member of the Association of Gynecological Endocrinologists of Russia, Russian Association of Endocrinologists, International Association of Obstetricians, Gynecologists and Endocrinologists |
Uvarova Elena Vitalievna | Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honored Scientist of the Russian Federation, Head of the 2nd Gynecological Department at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Professor at the Department of Obstetrics, Gynecology and Reproductology of the Institute of Professional Education at the I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of Health of the Russian Federation, Chief Freelance Pediatric and Adolescent Gynecologist of the Ministry of Health of the Russian Federation, President of the Association of Pediatric and Adolescent Gynecologists of Russia, member of the Russian Society of Obstetricians and Gynecologists |
Khaschenko Elena Petrovna | Candidate of Medical Sciences, Leading Researcher at the 2nd Gynecological Department of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Chief Freelance Pediatric and Adolescent Gynecologist of the Ministry of Health of the Russian Federation in the Central Federal District |
Chernukha Galina Evgenyevna | Doctor of Medical Sciences, Professor, Chief Researcher at the Department of Gynecological Endocrinology of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, President of the Interregional Public Organization "Association of Gynecological Endocrinologists" |
Yarmolinskaya Maria Igorevna | Professor of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Head of the Department of Gynecology and Reproductive Endocrinology at the D.O. Ott Research Institute of Obstetrics and Gynecology, Professor at the Department of Obstetrics and Gynecology at the I.I. Mechnikov North-Western State Medical University of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists |
All members of the working group are members of the Russian Society of Obstetricians and Gynecologists, unless specified otherwise.
Conflict of interest:
All members of the working group declare no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Obstetrician-gynecologists, endocrinologists, general practitioners, family physicians;
Students, residents, postgraduate students;
Faculty members, researchers.
In these clinical guidelines, all information is ranked according to the level of confidence of the recommendations and reliability of evidence based on the quantity and quality of studies on the issue (Table 3, Table 4, Table 5).
Table 3. Scale for assessing the levels of evidence reliability (LER) for diagnostic methods (diagnostic interventions)
LoE | Definition |
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 4. Scale for assessing the levels of evidence (LE) for preventive, therapeutic and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)
LoE | Definitions |
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 5. Scale for assessing the levels of confidence of recommendations (LCR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)
GoR | Definition |
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
These clinical guidelines were developed taking into account the following regulatory legal documents:
1) Order of the Russian Ministry of Health No. 1130n dated October 20, 2020 "On Approval of the Procedure for Providing Medical Care in the Profile "Obstetrics and Gynecology" (Registered with the Ministry of Justice of Russia on November 12, 2020, No. 60869);
2) Procedure for the use of assisted reproductive technologies, contraindications and restrictions on their use (Order of the Ministry of Health of the Russian Federation No. 803n dated July 31, 2020).
Appendix A3.1. Criteria for overweight and obesity in various populations
Race | Caucasians | Asians |
Overweight | BMI = 25.0–29.9 kg/m2 | BMI = 23.0–24.9 kg/m2 |
Obesity | BMI ≥ 30 kg/m2 (39) | BMI ≥ 27.5 kg/m2 (39) |
Appendix A3.2 Differential diagnosis of PCOS with other nosologies
Diseases and conditions with some manifestations overlapping with PCOS symptoms
Diseases and conditions | Clinical manifestations | Tests allowing differential diagnosis |
Pregnancy | Amenorrhea (rather than oligomenorrhea), other symptoms of pregnancy | Blood serum human chorionic gonadotropin (free beta-subunit) test Urine pregnancy test for human chorionic gonadotropin (positive) |
Hypothalamic amenorrhea | Amenorrhea, weight loss / low body mass index (BMI), history of intensive physical exercise, clinical signs of hyperandrogenism not typical, multifollicular ovaries sometimes detected | Blood serum luteinizing hormone level test Blood serum follicle-stimulating hormone test (decreased or at the lower limit of normal), blood total estradiol test (decreased) |
Premature ovarian insufficiency | Amenorrhea combined with symptoms of estrogen deficiency, including hot flashes and urogenital symptoms | Blood serum follicle-stimulating hormone (FSH) level test (elevated), blood total estradiol level test (decreased) |
Androgen-secreting tumors | Virilization (including voice changes, androgenetic alopecia, clitoromegaly), rapid onset of symptoms | Blood total testosterone level test Blood dehydroepiandrosterone sulfate (DHEA-S) level test (significantly elevated) Complex pelvic ultrasound (transvaginal and transabdominal) Magnetic resonance imaging (MRI) of the adrenal glands |
Cushing's syndrome or Cushing's disease | Along with clinical manifestations similar to PCOS (central obesity, hyperandrogenism, impaired glucose tolerance), there are more specific symptoms: often on the face — "moon face" with a simultaneous decrease in the upper and lower extremities in girth due to muscle and adipose tissue atrophy, "matronism" (a bright cyanotic flush combined with rounded facial features), slanted buttocks (due to muscle atrophy), wide (often > 1 cm) purplish-red striae on the abdomen, inner thighs and shoulders, in women — on the mammary glands, multiple subcutaneous hemorrhages occurring even with minor trauma, and other manifestations | 24-hour urinary free cortisol level test (elevated), salivary free cortisol level test (elevated), overnight low-dose dexamethasone suppression test (inadequate suppression of morning blood serum cortisol level) |
Acromegaly | Specific symptoms: headache, visual field defects, enlargement of the jaw, tongue, shoe and glove size | Blood insulin-like growth factor 1 (IGF-1) level test (elevated) Pituitary MRI |
Examples of PCOS diagnosis justification
PCOS (hirsutism, hyperandrogenemia, oligo-anovulation, polycystic ovaries on ultrasound)
PCOS (hirsutism, oligo-anovulation, polycystic ovaries on ultrasound)
PCOS (hyperandrogenemia, oligo-anovulation, polycystic ovaries on ultrasound)
PCOS (hirsutism, polycystic ovaries on ultrasound)
PCOS (hyperandrogenemia, polycystic ovaries on ultrasound)
PCOS (hirsutism, hyperandrogenemia, polycystic ovaries on ultrasound)
PCOS (oligo-anovulation, polycystic ovaries on ultrasound)
Appendix B. Physician Action Algorithms
PCOS Diagnosis
1 — blood testosterone level test; 2 — blood sex hormone-binding globulin (SHBG) level test; 3 — free androgen index; 4 — complex pelvic ultrasound (transvaginal and transabdominal); 5 — blood prolactin level test; 6 — blood thyroid-stimulating hormone (TSH) level test; 7 — blood free thyroxine level test; 8 — blood 17-hydroxyprogesterone level test.
1 — blood testosterone level test; 2 — blood sex hormone-binding globulin (SHBG) level test; 3 — free androgen index; 4 — complex pelvic ultrasound (transvaginal and transabdominal); 5 — blood prolactin level test; 6 — blood thyroid-stimulating hormone (TSH) level test; 7 — blood free thyroxine level test; 8 — blood 17-hydroxyprogesterone level test.
Appendix C. Patient Information
Polycystic ovary syndrome (PCOS) is the most common hormonal and reproductive disorder affecting women of reproductive age. Statistics show that 8% to 21% of women suffer from this condition.
A diagnosis of PCOS can be made if at least 2 of the following criteria are met:
prolonged absence of ovulation;
elevated androgen (male hormone) levels;
multiple small cysts in the ovaries.
PCOS develops as a result of multiple factors. Many women with PCOS have insulin resistance, a condition where the body cannot use insulin effectively. This leads to high levels of circulating insulin in the blood, known as hyperinsulinemia. Hyperinsulinemia is believed to be linked to elevated androgen levels, as well as obesity and type 2 diabetes mellitus. In turn, obesity can increase insulin levels, worsening PCOS.
Ovulation is the process by which mature (fertilization-ready) eggs are released from the ovaries. In ovulatory disorders, the female reproductive system does not produce adequate hormones required for egg development. When the ovaries fail to produce the hormones necessary for ovulation and a normal menstrual cycle, they enlarge and develop numerous small cysts that produce androgens. Elevated androgen levels may not affect the menstrual cycle; some women with PCOS have a normal menstrual cycle.
Signs and symptoms of PCOS are associated with hormonal imbalance, anovulation, and insulin resistance, and may include:
irregular, infrequent, or absent menstruation;
hirsutism — excessive hair growth on the body and face, including the chest, abdomen, etc.;
acne and oily skin;
enlarged ovaries with multiple cysts on the surface;
infertility;
overweight or obesity, particularly around the waist (central obesity) and abdomen;
male-pattern baldness or hair thinning;
darkened patches of skin on the neck, in the armpits, and under the breasts.
PCOS symptoms can mimic other medical conditions, so always consult your physician for differential diagnosis.
PCOS Diagnosis
In addition to a comprehensive medical history and physical examination, diagnostic procedures for PCOS may include:
gynecological examination — external and internal examination of the female reproductive organs;
ultrasound — a diagnostic imaging method that uses high-frequency sound waves and a computer to generate images of blood vessels, tissues, and organs. Ultrasound can determine whether a woman's ovaries are enlarged, whether cysts are present, and assess endometrial thickness. Transvaginal ultrasound, in which an ultrasound probe is inserted into the vagina, is sometimes used to visualize the endometrium;
blood tests to measure androgen and other hormone levels.
PCOS Management
Specific treatment for PCOS will be determined by your physician based on your age, overall health and medical history, severity of the disorder, underlying causes, symptoms, tolerance to medications or procedures, your opinions and preferences, and treatment expectations.
PCOS management also depends on whether the woman desires to become pregnant. For women wishing to conceive, treatment aims at weight reduction and ovulation induction. This may include:
measures for weight reduction — healthy nutrition and increased physical activity. These measures will also help the body utilize insulin more efficiently, lower blood glucose levels, and may help normalize ovulatory regularity in women;
prescription of medications for ovulation induction, which help the ovaries produce one or more follicles and release a mature egg ready for fertilization in a timely manner.
Women often struggle long-term with the physical changes caused by PCOS, which include excessive body hair growth, acne, and weight gain. As an adjunct to diet and medication, electrolysis and laser hair removal can be helpful in boosting a woman's self-confidence.
Due to the potential long-term risks associated with PCOS (heart disease, type 2 diabetes mellitus), women with this condition should consult their physician regarding appropriate management.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Appendix G1. Ferriman-Gallwey scale
Russian title: Ferriman-Gallwey scale
Original title (if applicable): Ferriman-Gallwey score
Source (official developer website, validation publication): Yildiz et al., 2010
Type (underline): rating scale
Purpose: Assessment of the severity of hirsutism
Content (template): The severity of hair growth is assessed in 9 body areas on a 4-point scale
Fig. 1. Modified Ferriman-Gallwey scale (Yildiz et al., 2010)
Key (interpretation): The sum of scores across all areas is called the hirsutism score.
Notes: It is recommended not to use depilation or wax hair removal for at least 4 weeks and to avoid shaving hair for at least 5 days prior to the study.
Appendix G2. Age characteristics of pubertal stages in girls (according to Tanner J.M., Marshal W.A., 1969)
Russian title: Age characteristics of girls' puberty stages
Original title (if any): Tanner Stages
Source (official developer website, validated publication): Hamlin A., Robertson M., Wilson D. R. Tanner Stages and Pubertal Development // Journal of Pediatric Surgical Nursing. – 2022
Type (underline): rating scale
Purpose: Assessment of the degree of secondary sexual characteristics development
Content (template): The degree of secondary sexual characteristics development is assessed by stages (breast development and pubic hair growth)
Key (interpretation): Correspondence of secondary sexual characteristics development to the patient's age
Explanations: If the development of secondary sexual characteristics does not correspond to the patient's age, a diagnosis of puberty disorder is established
C t a d i stage | Image | Breast development, signs | Pubic hair growth, signs | Mean age, years |
I |
| Prepubertal, no glandular tissue, areolar diameter less than 2 cm, areolae pale, enlargement of the nipple only. | Prepubertal, absence of hair. | Prepubertal period |
II |
| Appearance of breast glandular tissue, hardening of the mammary glands noticeable or palpable, the gland begins to protrude above the chest surface, increase in areolar diameter. | Sparse hair, long, straight or slightly curly, minimally pigmented hair, mostly on the labia majora. | 10,5-11,5 |
III |
| Further enlargement of the breasts and areolas without demarcation of their contours, the breasts and areolas protrude as a cone, with no boundary between them, areolar pigmentation appears. | Darker and coarser hair spreading across the pubis. | 12,0-12,5 |
IV |
| Protrusion of the areola and nipple above the mammary gland, the areola is intensely pigmented, protruding as a second cone above the breast tissue. | Dense, adult-type hair not spreading to the medial surface of the thighs. | 13,0-13,5 |
V |
| Adult breast contours with protrusion of the nipple only, the contour between the breast tissue and the areola is smoothed out. | Adult-type hair spreading in the shape of a classical triangle. | 14,0-15,0 |
