Diagnosis of polycystic ovary syndrome in adults

INTRODUCTION — The polycystic ovary syndrome (PCOS) is an important cause of both menstrual irregularity and androgen excess in women. PCOS can be readily diagnosed when women present with the classic features of hirsutism, irregular menstrual cycles, and polycystic ovarian morphology on transvaginal ultrasound (TVUS). However, there has been considerable controversy about specific diagnostic criteria when not all of these classic features are evident.

The diagnosis of PCOS will be reviewed here. The epidemiology and pathogenesis, clinical manifestations, and treatment of PCOS are described in detail separately. The diagnosis of PCOS in adolescents is also reviewed separately. (See "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults" and "Clinical manifestations of polycystic ovary syndrome in adults" and "Treatment of polycystic ovary syndrome in adults" and "Diagnostic evaluation of polycystic ovary syndrome in adolescents".)

CLINICAL FEATURES — The clinical features of PCOS are described here briefly but are reviewed in detail separately. (See "Clinical manifestations of polycystic ovary syndrome in adults".)

PCOS is thought to be one of the most common endocrinopathies in women, affecting between 5 and 10 percent of women, depending upon the population studied [1]. (see "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults", section on 'Epidemiology'). The syndrome is characterized clinically by oligomenorrhea and hyperandrogenism, as well as the frequent presence of associated risk factors for cardiovascular disease, including obesity, glucose intolerance, dyslipidemia, fatty liver, and obstructive sleep apnea. Other features include:

●Menstrual dysfunction – The menstrual irregularity typically begins in the peripubertal period, and menarche may be delayed. The menstrual pattern is typically one of oligomenorrhea (fewer than nine menstrual periods in a year) and, less often, amenorrhea (no menstrual periods for three or more consecutive months). Women with PCOS often experience more regular cycles after age 40 years. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Menstrual dysfunction'.)

●Hyperandrogenism – Hyperandrogenism may include clinical signs (hirsutism, acne, male-pattern hair loss) and/or elevated serum androgen concentrations (ie, hyperandrogenemia) (see "Female pattern hair loss (androgenetic alopecia in females): Pathogenesis, clinical features, and diagnosis"). Most women with PCOS have both clinical and biochemical evidence of hyperandrogenism. Signs of more severe androgen excess (virilization), such as deepening of the voice and clitoromegaly, occur rarely and suggest the possibility of ovarian hyperthecosis or an androgen-secreting tumor. (See 'Severe hyperandrogenism/virilization' below.)

Hirsutism is defined as excess terminal (thick, pigmented) body hair in a male distribution and may be noted above the upper lip, chin, periareolar area, in the midsternum, and along the linea alba of the lower abdomen (picture 1). There is substantial racial variability in hirsutism; Asian women with PCOS, as an example, have a lesser degree of hirsutism, than do non-Hispanic White or Black women. (See "Pathophysiology and causes of hirsutism", section on 'Ethnicity'.)

●Polycystic ovaries – The typical polycystic appearance of the ovaries is seen on transvaginal ultrasound (TVUS) in the majority of women with irregular menses and hyperandrogenism. However, this ultrasound appearance is nonspecific as it may also be seen in normal-cycling women. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Ultrasound appearance'.)

●Metabolic issues/cardiovascular risks – Approximately 40 to 85 percent of women with PCOS are overweight or obese compared with age-matched controls [2]. Insulin resistance is present in both lean and obese women with PCOS (30 and 70 percent, respectively) compared with age- and weight-matched controls [2].

●Women with PCOS are also at increased risk for type 2 diabetes. There are concerns that women with PCOS are at higher risk than women without PCOS for coronary heart disease, independent of traditional cardiovascular risk factors, but data are inconclusive. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'IGT/type 2 diabetes' and "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Coronary heart disease'.)

●Other clinical manifestations related to PCOS include nonalcoholic steatohepatitis and sleep apnea. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Nonalcoholic fatty liver disease' and "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Sleep apnea'.)

●Mood – There is evidence that PCOS is associated with mood disorders (depression and anxiety), impaired quality of life, and eating disorders (binge eating, even when compared with women with the same body mass index [BMI]). (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Psychosocial issues'.)

EVALUATION

When to suspect PCOS — The diagnosis of PCOS should be suspected in any women of reproductive age who presents with irregular menses and symptoms of hyperandrogenism (acne, hirsutism, male-pattern hair loss). The presence of overweight or obesity should further raise suspicion. Some women present with either oligomenorrhea or hyperandrogenic symptoms alone. They should also be evaluated for PCOS, particularly those with hyperandrogenism (as most women with hirsutism have PCOS). Women with polycystic ovaries on ultrasound and no other clinical features of PCOS (hyperandrogenism or menstrual dysfunction) do not have PCOS and need no further evaluation. (See 'Transvaginal ultrasound' below.)

Lastly, it is important to have a high index of suspicion for PCOS because these women may have associated risk factors for cardiovascular disease, including obesity, glucose intolerance, dyslipidemia, fatty liver, and obstructive sleep apnea that require evaluation and treatment. (See 'Cardiometabolic risk assessment' below.)

Delays in diagnosis — Early diagnosis and intervention are important in women with PCOS for quality of life and well-being. However, most women with PCOS describe a poor diagnosis experience related to long delays and inadequate health information [3]. In a cross-sectional, international study of diagnosis experiences in over 1300 women with PCOS (using online questionnaires), almost half saw three or more health professionals prior to diagnosis, and for one-third, it took over two years before their diagnosis was made [4]. In addition, only 16 percent were satisfied with the health information and educational materials they received. These observations highlight opportunities for improving care for women with PCOS.

History and physical — Using the Rotterdam criteria, many patients can be diagnosed based upon the history and physical (eg, a history of irregular menses and clinical signs of hyperandrogenism: acne, hirsutism, and/or male-pattern hair loss). As noted above, irregular menses typically begin in the teenage years. Women who develop oligomenorrhea at a much later age (eg, >30 years) are less likely to have PCOS. (See "Evaluation and management of secondary amenorrhea".)

We suggest using the Ferriman-Gallwey score to assess the degree of hirsutism on physical exam (figure 1). However, there are a number of limitations to this approach in clinical practice. Most importantly, the expression of hair growth varies among racial groups. Most East Asian and Native American women have little body hair, White and Black women have an intermediate amount, and most Mediterranean, South Asian, and Middle Eastern women have substantially greater quantities of body hair, even though serum androgen concentrations are similar in all groups. Therefore, even a minimal amount of acne or facial hair in an East Asian or Native American women should raise suspicion for a hyperandrogenic disorder, most commonly, PCOS.

Women with evidence of virilization and/or hirsutism of recent onset that is rapidly progressive need immediate evaluation for the most serious causes of hyperandrogenism (ovarian and adrenal androgen-secreting tumors). (See 'Severe hyperandrogenism/virilization' below and 'Androgen-secreting tumors/ovarian hyperthecosis' below.)

Biochemical testing

Women with hyperandrogenism — We suggest measuring serum androgens in women with hyperandrogenic symptoms (with or without oligomenorrhea). Most women who present with hirsutism have PCOS, but it is essential to identify those who have other disorders such as NCCAH, or a more serious cause (androgen-secreting tumors and ovarian hyperthecosis). The approach to ruling out other disorders is similar to the evaluation of women with hirsutism, 75 to 80 percent of whom have PCOS.

Normal menstrual cycles — Women with hyperandrogenic symptoms (most commonly hirsutism) and normal menstrual cycles are most likely to fall into the category of PCOS or idiopathic hirsutism and are unlikely to have a more serious cause for their hirsutism. For these women, we suggest measuring only a serum total testosterone. (See "Evaluation of premenopausal women with hirsutism", section on 'Hirsutism and normal menstrual cycles'.)

Oligomenorrhea — For women with hyperandrogenic symptoms and oligomenorrhea, we suggest measuring a serum total testosterone, an early morning 17-hydroxyprogesterone, and routine labs to investigate other causes of irregular menses. (See "Evaluation of premenopausal women with hirsutism", section on 'Hirsutism with oligomenorrhea/amenorrhea'.)

●Total testosterone – In women with clinical evidence of hyperandrogenism (hirsutism, acne, or male-pattern hair loss on exam), we suggest measuring serum total testosterone. Serum total testosterone is best assessed by liquid chromatography-tandem mass spectroscopy (LC-MS/MS), an accurate and specific method. With LC-MS/MS, the upper limit of normal for serum testosterone in women is in the 45 to 60 ng/dL range (1.6 to 2.1 nmol/L); women with a serum testosterone >150 ng/dL require evaluation for the most serious causes of hyperandrogenism (ovarian and adrenal androgen-secreting tumors) (see 'Severe hyperandrogenism/virilization' below). The immunoassays that are available in most hospital laboratories are not suitable to accurately measure testosterone in women. (See "Evaluation of premenopausal women with hirsutism", section on 'Hirsutism with oligomenorrhea/amenorrhea'.)

●Other androgens

•Free testosterone – We do not suggest the routine measurement of serum free testosterone. Some groups do recommend measuring free testosterone instead of or in addition to total testosterone because it may be the most sensitive test to establish the presence of hyperandrogenemia. However, commercially available free testosterone assays are currently unreliable. If measured, it should be done in a laboratory that measures it by equilibrium dialysis.

Another option, although less good, is to order free testosterone from a laboratory that calculates it from total testosterone and sex hormone-binding globulin (SHBG) measurements using a formula demonstrated to give results that agree closely with those of equilibrium dialysis [5,6]; laboratories that use other formulae should not be used, since other formulae give spuriously high results [7].

Direct measurement of SHBG is helpful in other ways. In women with PCOS, an abnormally low SHBG is a risk factor for increased biologically active testosterone and, hence, a more severe phenotype [8].

•DHEAS – We do not suggest the routine measurement of dehydroepiandrosterone sulfate (DHEAS) in women thought to have PCOS, because mildly elevated levels of DHEAS are unlikely to affect management.

However, we do suggest measuring DHEAS in severe hyperandrogenism because it can be extremely high in adrenocortical carcinoma. (See 'Severe hyperandrogenism/virilization' below.)

•Androstenedione – The role of serum androstenedione in the evaluation of PCOS and/or hirsutism is unclear [9]. However, its measurement in some populations with PCOS, for example, Icelandic women, may be important for documenting hyperandrogenism [10]. Two studies have reported isolated elevations of serum androstenedione concentrations in women with PCOS, but the percent of women with this biochemical pattern is variable (20 of 86 [23 percent] [11] and 49 of 1128 [4.1 percent] [12]). In the smaller study, serum androstenedione was negatively associated with insulin sensitivity. (See "Clinical manifestations of polycystic ovary syndrome in adults".)

●Serum 17-hydroxyprogesterone – We suggest measuring a morning serum 17-hydroxyprogesterone in the early follicular phase in all women with possible PCOS to rule out nonclassic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. For women who have some spontaneous menstrual cycles, this should be done in the early follicular phase, while for those without cycles, it can be drawn on a random day.

The clinical presentation of NCCAH can be similar if not identical to that of PCOS (hyperandrogenism, oligomenorrhea, and polycystic ovaries). NCCAH is less common than PCOS but should be ruled out because there are risks that offspring could be affected with the more severe classic 21-hydroxylase deficiency (table 1). It is particularly important to test women of Eastern European Jewish descent (who have a 1:27 prevalence) and women of Hispanic, Slavic, or Italian descent, in whom the prevalence is 1:40, 1:50, and 1:300 women, respectively [13]. (See "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on 'Genetic testing'.)

●Tests to rule out other causes of oligomenorrhea – In any woman with oligomenorrhea/oligo-ovulation, other causes of irregular menses should be investigated. Testing should include human chorionic gonadotropin (hCG), prolactin, thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). In general, it is not necessary to measure luteinizing hormone (LH); an elevated LH-to-FSH ratio is not a criterion for the diagnosis of PCOS. (See "Evaluation and management of secondary amenorrhea", section on 'Initial evaluation'.)

In the past, many clinicians measured LH and FSH and used an elevated LH:FSH ratio ≥2 as evidence for the diagnosis of PCOS. However, the LH:FSH ratio was never a criterion for the diagnosis, and its use can be misleading (eg, if there has been a recent ovulation, LH will be suppressed and the ratio will be ≤2:1).

●Anti-müllerian hormone (AMH) – Serum AMH concentrations are generally in the upper range of normal or markedly elevated in women with PCOS [14-16]. At this time, AMH assays are limited by the absence of an international standard; AMH is not currently part of the laboratory evaluation of PCOS.

Already taking pharmacologic therapy — Some women with hirsutism seek advice when they are already taking pharmacotherapy, usually estrogen-progestin oral contraceptives. Measuring serum androgens is generally not useful in this setting, because oral contraceptives suppress serum gonadotropins and ovarian androgens, most importantly, testosterone. Androgen measurements should also not be obtained when women are on metformin or spironolactone, as the interpretation of the result is confounded by the effects of these medications on androgen levels. In general, we ask women stop their medications at least four to six weeks before measuring serum androgens. (See "Evaluation of premenopausal women with hirsutism", section on 'Women already taking pharmacologic therapy'.)

Severe hyperandrogenism/virilization — For women with features of severe hyperandrogenism (virilization and/or hirsutism of recent onset that is rapidly progressive), we suggest measuring serum total testosterone, ideally using LC-MS/MS in a laboratory that participates in the Centers for Disease Control and Prevention (CDC)'s Hormone Standardization Program (HoSt), and serum DHEAS. These women usually have an androgen-secreting tumor (ovarian or adrenal) or ovarian hyperthecosis (although both are more common in post- than premenopausal women). (See "Evaluation of premenopausal women with hirsutism", section on 'Additional evaluation for severe hyperandrogenemia'.)

Women with features of other endocrine disorders — On occasion, women with other endocrine disorders, such Cushing's syndrome, can present with features similar to those of PCOS (oligomenorrhea, hirsutism, and obesity). However, they typically also have symptoms and signs suggestive of cortisol excess, such as centripetal obesity, hypertension, purple striae, and proximal muscle weakness. Further evaluation is necessary in these cases to distinguish between the two disorders. (See "Evaluation of premenopausal women with hirsutism", section on 'Women with features of other endocrine disorders' and "Establishing the diagnosis of Cushing syndrome".)

Transvaginal ultrasound — Transvaginal ultrasound (TVUS) is performed in some women to determine if they have polycystic ovarian morphology (PCOM, eg, the appearance of PCOS on ultrasound). However, not all women with possible PCOS undergo ultrasound. If the patient has both oligomenorrhea and evidence of hyperandrogenism and causes other than PCOS have been ruled out, she meets criteria for the diagnosis of PCOS, and an ultrasound is not necessary. In women with hyperandrogenic symptoms and normal menstrual cycles, TVUS is often done to look for PCOM (see 'Diagnosis' below). The transvaginal, rather than transabdominal, approach should be used whenever possible.

The ultrasound criteria for polycystic ovaries or PCOM have evolved since the first ultrasound description in 1986. It is important to note that follicle number and size, not cysts, are relevant to an ultrasound diagnosis. The Rotterdam criteria, considered to have sufficient specificity and sensitivity to define PCOM, include the presence of 12 or more follicles in either ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume (>10 mL; calculated using the formula 0.5 x length x width x thickness). One ovary fitting this definition is sufficient to define PCOM. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Ultrasound appearance'.)

However, in some reports, over 50 percent of normal-cycling women met the threshold of 12 or more small follicles in each ovary [17], prompting experts to revisit the validity of the 2003 Rotterdam ultrasound criteria. A number of alternative criteria have since been proposed, but there is currently no consensus on the optimal ultrasound criteria.

●Based upon a 2014 systematic review, a higher threshold (≥25 follicles per ovary) has been proposed but only if the clinician uses a transducer frequency that provides maximal resolution (eg, ≥8 MHz) [18]. This technology is not readily available to most clinicians.

●In 2018, an international evidence-based medicine group recommended a threshold of ≥20 follicles in each ovary [19].

●Ovarian volume and follicle number decrease with age in women with or without PCOS. Age-based criteria to define polycystic ovaries have therefore been proposed [20-22].

Women are sometimes referred for PCOS based upon the incidental finding of cystic ovaries on pelvic ultrasound or other abdominal imaging. If there are no other clinical features of PCOS, no further evaluation is needed, as sonographically or radiographically detected polycystic ovaries are a nonspecific finding. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Ultrasound appearance'.)

DIAGNOSIS

Rotterdam criteria (preferred) — Most expert groups use Rotterdam criteria to make the diagnosis of PCOS [19,23].

Two out of three of the following criteria are required to make the diagnosis [24]:

●Oligo- and/or anovulation

●Clinical and/or biochemical signs of hyperandrogenism

●Polycystic ovaries (by ultrasound)

Many women with irregular menses and hyperandrogenic symptoms can be diagnosed based upon on the history and physical exam alone. However, the diagnosis of PCOS is only confirmed when other conditions that mimic PCOS are excluded (eg, disorders that cause oligo/anovulation and/or hyperandrogenism, such as thyroid disease, nonclassic congenital adrenal hyperplasia [NCCAH], hyperprolactinemia, and androgen-secreting tumors).

Other proposed criteria — Other proposed criteria include:

The 1990 National Institutes of Health (the NIH criteria), which allow for a clinical diagnosis without the use of an imaging study. In addition, the NIH criteria require the presence of irregular menses, while the other criteria do not [25].

In 2006, the Androgen Excess (AE) and PCOS Society proposed the AE-PCOS Criteria (table 2) [26]. In contrast to the Rotterdam criteria, the majority of the AE-PCOS task force agreed that there were insufficient data to define women with ovulatory dysfunction and polycystic ovaries, but no evidence of hyperandrogenism, as having PCOS [26].

The use of multiple classification systems creates confusion for clinicians and patients. A summary report from the NIH Evidence-based Methodology Workshop on PCOS in December 2012 concluded that the Rotterdam criteria should be adopted for now because it is the most inclusive [27]. They also suggested that the name "PCOS" be changed because it focuses on polycystic ovarian morphology (PCOM), which is neither sufficient nor necessary for the diagnosis, and the fluid-filled structures in the ovary are not "cysts." One proposed name is the "metabolic reproductive syndrome," which reflects the multifaceted nature of the syndrome but the Workshop participants acknowledge the difficulty changing the name.

Postmenopausal women — The 2013 Endocrine Society Clinical Practice Guidelines for the Diagnosis and Treatment of Polycystic Ovary Syndrome suggest using the Rotterdam criteria for diagnosing PCOS in adult premenopausal women [23]. They acknowledge that establishing the diagnosis in postmenopausal women is problematic but suggest that a presumptive diagnosis can be based upon a "well-documented long-term history of oligomenorrhea and hyperandrogenism during the reproductive years." They note that the finding of PCOS morphology on pelvic ultrasound would provide additional support.

However, ovarian volume and follicle number decrease with age in women with or without PCOS. While age-based criteria for PCOS have been proposed for women over age 40 years [20], there currently are no well-established criteria in postmenopausal women. However, when postmenopausal women present with new-onset or worsening hirsutism, or other symptoms of severe hyperandrogenism, transvaginal ultrasound (TVUS) should always be performed to rule out disorders such as ovarian hyperthecosis and androgen-secreting tumors. (See 'Severe hyperandrogenism/virilization' above.)

DIFFERENTIAL DIAGNOSIS — The diagnosis of PCOS is confirmed once other conditions with features similar to PCOS have been excluded, such as nonclassic congenital adrenal hyperplasia (NCCAH), thyroid disease, and hyperprolactinemia. Women with severe hyperandrogenism and virilization require a more extensive evaluation for the most serious causes of androgen excess (androgen-secreting ovarian and adrenal tumors and ovarian hyperthecosis) [23]. (See 'Severe hyperandrogenism/virilization' above.)

NCCAH — The clinical presentation of nonclassic congenital adrenal hyperplasia (NCCAH) is similar or identical to that of PCOS (hyperandrogenism, oligomenorrhea, and polycystic ovaries). NCCAH is less common than PCOS but should be ruled out because there are risks that offspring could be affected with the more severe classic 21-hydroxylase deficiency (table 1). We suggest testing for NCCAH deficiency by measuring 17-hydroxyprogesterone at 8 AM. This test is most important in high-risk women, including Mediterranean, Hispanic, and Ashkenazi Jewish women.

A value less than 200 ng/dL (6 nmol/L) in the early follicular phase makes this diagnosis unlikely. A morning value of 17-hydroxyprogesterone greater than 200 ng/dL in the early follicular phase strongly suggests the diagnosis, which may be confirmed by a high-dose (250 mcg) corticotropin (ACTH) 1-24 (cosyntropin) stimulation test. The response to cosyntropin is exaggerated, with most patients having values exceeding 1500 ng/dL (43 nmol/L). (See "Diagnosis and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase deficiency", section on '17-hydroxyprogesterone'.)

Androgen-secreting tumors/ovarian hyperthecosis — Women with androgen-secreting ovarian or adrenal tumors or ovarian hyperthecosis typically present with recent onset of severe hirsutism, sudden progressive worsening of hirsutism, and symptoms or signs of virilization, including frontal balding, severe acne, clitoromegaly, increased muscle mass, or deepening of the voice.

Their serum testosterone concentrations are almost always greater than 150 ng/dL (5.2 nmol/L) [28], and those with adrenal tumors typically have serum dehydroepiandrosterone sulfate (DHEAS) concentrations higher than 800 mcg/dL (21.6 micromol/L). While all of these disorders occur primarily in postmenopausal women, they are occasionally seen in premenopausal women. (See "Evaluation of premenopausal women with hirsutism", section on 'Additional evaluation for severe hyperandrogenemia' and "Ovarian hyperthecosis".)

Other — Oligomenorrhea can be seen with hypothyroidism, hyperthyroidism, and hyperprolactinemia. However, hyperandrogenic symptoms are not common features of these disorders. These disorders are distinguished by their clinical features and biochemical testing (high TSH, low TSH, high prolactin). (See "Epidemiology and causes of secondary amenorrhea".)

FURTHER EVALUATION AFTER DIAGNOSIS — Once the diagnosis of PCOS is made, we suggest additional evaluation, including a cardiometabolic risk assessment, as well as screening for mood disorders, fatty liver, and obstructive sleep apnea by polysomnography. For women pursuing fertility, we suggest assessment of ovulatory status using the menstrual history and, if needed, serum progesterone measurement and/or transvaginal ultrasound (TVUS).

Cardiometabolic risk assessment

Cardiovascular — There is a high prevalence of obesity and insulin resistance among women with PCOS; they are at increased risk for type 2 diabetes, dyslipidemia, and coronary heart disease (CHD) (see "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Metabolic issues'). Therefore, we suggest the following assessments:

●Blood pressure and body mass index (BMI) at initial diagnosis and thereafter. Waist circumference should also be measured.

●Fasting lipid profile at initial diagnosis.

●A two-hour oral glucose tolerance test (OGTT) (with measurement of fasting and two-hour glucose) in all women with PCOS at initial diagnosis. If this is not feasible, a fasting glucose should be obtained together with a measurement of the glycated hemoglobin (A1C) concentration. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults", section on 'Diabetes'.)

This approach is consistent with a number of professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), American Association of Clinical Endocrinologists (AACE) [29], the Androgen Excess Society [30], and a consensus panel representing the European Society of Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM) [24].

The rationale for an OGTT is that a standard fasting glucose measurement lacks the sensitivity to detect impaired glucose tolerance or early type 2 diabetes that will be present on an OGTT in a substantial number of women with PCOS. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'IGT/type 2 diabetes' and "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults".)

We agree with the Androgen Excess Society and also suggest the following [30]:

•Patients with normal glucose tolerance should be rescreened at least once every two years or more frequently if additional risk factors are identified.

•Patients with impaired glucose tolerance should be screened annually for development of type 2 diabetes.

●No tests of insulin resistance are necessary to make the diagnosis of PCOS, nor are they needed to select treatments [24,31]. Additionally, there currently is no validated test for measuring insulin resistance in a clinical setting. The hyperinsulinemic-euglycemic clamp and the frequently sampled intravenous glucose tolerance test are research procedures. While calculated indices using fasting insulin and glucose concentrations are sometimes used (eg, glucose-to-insulin ratios, homeostasis model assessment of insulin resistance [HOMA-IR or HOMA]), there are limitations to their use, including changes in beta cell function over time, lack of a standardized universal insulin assay, and lack of data demonstrating that markers of insulin resistance predict response to treatment. As a result, we do not recommend routine assessment of insulin resistance.

Sleep apnea — Obstructive sleep apnea is common in women with PCOS. Therefore, women with PCOS should be questioned about signs and symptoms of sleep apnea (snoring, excessive daytime sleepiness, morning headaches). If signs and symptoms suggest the diagnosis, the patient should be referred to a sleep medicine clinician. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Sleep apnea'.)

Role of transvaginal ultrasound — Women with PCOS are at increased risk of anovulation and infertility; in the absence of anovulation, the risk of infertility is uncertain.

●In women who are ready to conceive, TVUS is used in those with anovulatory infertility undergoing ovulation induction to monitor follicular growth and number. (See "Treatment of polycystic ovary syndrome in adults", section on 'Women pursuing pregnancy'.)

●By contrast, we suggest against the routine use of ultrasound in premenopausal women with PCOS to screen for the presence of endometrial hyperplasia or cancer. This is because the utility of ultrasound for excluding endometrial abnormalities in premenopausal women (unlike postmenopausal women) has not been established. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Endometrial cancer risk' and "Overview of the evaluation of the endometrium for malignant or premalignant disease", section on 'Premenopausal patients with abnormal bleeding'.)

Nonalcoholic fatty liver disease — Although women with PCOS appear to be at increased risk for nonalcoholic fatty liver disease (NAFLD), we do not suggest routine screening for this disorder [32]. Current guidelines do not recommend screening for any groups at high risk for this disorder (eg, individuals with obesity or type 2 diabetes), because there are uncertainties around which diagnostic test to use (since liver enzyme levels may be normal in patients with NAFLD), how to treat NAFLD if discovered, and whether screening is cost effective. However, lifestyle changes are currently the focus of management. (See "Epidemiology, clinical features, and diagnosis of nonalcoholic fatty liver disease in adults", section on 'Screening'.)

Depression and anxiety disorders — Women with PCOS may be more likely to have mood disorders (depression and anxiety) when compared with women of similar BMI without PCOS. They are also at risk for eating disorders (binge eating). We agree with a number of expert societies and suggest screening all women with PCOS for depression and anxiety [19,23,31]. The best approach is to use brief, validated screening tools such as the Patient Health Questionnaire (PHQ)-9 for depression (table 3) and the Generalized Anxiety Disorder 7 (GAD-7) anxiety scale for anxiety disorders (table 4). These are simple questionnaires that patients can fill out prior to or during an outpatient visit. (See "Screening for depression in adults" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Screening, assessment, and diagnosis'.)

The PHQ-2 is a briefer and somewhat less accurate option to the PHQ-9. The PHQ-2 is comprised of the first two questions from the PHQ-9 (see "Screening for depression in adults"):

●During the last month, have you often been bothered by feeling down, depressed, or hopeless?

●During the last month, have you often been bothered by having little interest or pleasure in doing things?

The PHQ-2 has the advantage of easy verbal administration and may be administered asking for responses as yes/no or scaled 0 to 3. A single "yes" response or a score ≥3 (total score range 0 to 6) indicate possible depression.

Screening alone does not improve patient outcome. Clinicians must have a process in place to provide referral for additional evaluation and treatment to those with evidence of depression or generalized anxiety disorder on screening. Follow-up evaluation should ideally be done at the same site where screening occurs. (See "Screening for depression in adults" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Screening, assessment, and diagnosis'.)

Anovulatory infertility — Women with intermenstrual intervals >35 days are oligo-ovulatory and may require weight loss and/or ovulation induction agents to conceive. Serum progesterone can be measured to assess whether ovulation has occurred. In normally cycling women, this is done on day 21 of a cycle; documenting ovulation in women with long intermenstrual intervals is more challenging, but the goal is to draw the sample 7 to 10 days before the next menses is expected. Ultrasound can also be used to document ovulation. (See "Ultrasound evaluation of the normal menstrual cycle", section on 'Ovulation'.)

Fertility evaluation can be postponed until the patient is ready to pursue pregnancy. However, lifestyle changes such as weight loss and exercise should be instituted after diagnosis as lower BMI is associated with an improved likelihood of ovulation and conception. In obese women, weight loss is also associated with improved pregnancy outcomes. (See "Treatment of polycystic ovary syndrome in adults", section on 'Weight loss'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Polycystic ovary syndrome" and "Society guideline links: Hirsutism" and "Society guideline links: Classic and nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Polycystic ovary syndrome (The Basics)")

●Beyond the Basics topic (see "Patient education: Polycystic ovary syndrome (PCOS) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Characteristic clinical features – Polycystic ovary syndrome (PCOS) is characterized clinically by oligomenorrhea and hyperandrogenism, as well as the frequent presence of associated risk factors for cardiovascular disease, including obesity, glucose intolerance, dyslipidemia, and obstructive sleep apnea. (See 'Clinical features' above.)

●Evaluation for women with suspected PCOS – The diagnosis of PCOS should be suspected in any women of reproductive age who presents with irregular menses and symptoms of hyperandrogenism (acne, hirsutism, female pattern hair loss). The presence of overweight or obesity should further raise suspicion.

Most expert groups suggest initial measurement of a total testosterone concentration in women who present with hirsutism. If there are concerns about a possible androgen-secreting tumor or ovarian hyperthecosis causing the hyperandrogenism (onset of hirsutism at a late age with rapid progression, signs of virilization such as deepening of the voice or clitoromegaly), we suggest measuring serum dehydroepiandrosterone sulfate (DHEAS), as well as total testosterone to look for adrenal sources of hyperandrogenism. (See 'Women with hyperandrogenism' above.)

In women who meet only one of the two criteria (oligo-ovulation and hyperandrogenism), transvaginal ultrasound (TVUS) is performed to look for the presence of polycystic ovaries. (See 'Transvaginal ultrasound' above.)

●Diagnosis – The diagnosis of PCOS is currently made using the Rotterdam criteria. Two out of three of the following are required to make the diagnosis: oligomenorrhea, hyperandrogenism, and polycystic ovaries on ultrasound. However, not all experts agree that women with oligomenorrhea and polycystic ovaries, but not hyperandrogenism, should be considered to have PCOS (table 2). (See 'Rotterdam criteria (preferred)' above.)

●Additional evaluation after diagnosis is made

•Cardiometabolic risk assessment – Once the diagnosis of PCOS is made, cardiometabolic risk assessment should include measurement of blood pressure and body mass index (BMI), fasting lipid profile, and an oral glucose tolerance test (OGTT). (See 'Cardiometabolic risk assessment' above.)

•Depression and sleep apnea – Women with PCOS should be questioned about symptoms of depression, eating disorders, and sleep apnea as all are common in this population. (See 'Depression and anxiety disorders' above and 'Sleep apnea' above.)

•Fertility evaluation if desired – Women with intermenstrual intervals >35 days are oligo-ovulatory and may require weight loss and/or ovulation induction agents to conceive. Fertility evaluation can be postponed until the patient is ready to pursue pregnancy. (See 'Anovulatory infertility' above.)