Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
Diagnosis of Polycystic Ovary Syndrome (PCOS)
Diagnosis in Adults
The Task Force suggests that the diagnosis of PCOS be made if two of the three following criteria are met: androgen excess, ovulatory dysfunction, or polycystic ovaries (PCO) (see Tables 1 and 2 in the original guideline document), whereas disorders that mimic the clinical features of PCOS are excluded. These include, in all women: thyroid disease, hyperprolactinemia, and nonclassic congenital adrenal hyperplasia (primarily 21-hydroxylase deficiency by serum 17-hydroxyprogesterone [17-OHP]) (see Table 3 in the original guideline document). In select women with amenorrhea and more severe phenotypes, the Task Force suggests more extensive evaluation excluding other causes (see Table 4 in the original guideline document) (2|+++O).
Diagnosis in Adolescents
The Task Force suggests that the diagnosis of PCOS in an adolescent girl be made based on the presence of clinical and/or biochemical evidence of hyperandrogenism (after exclusion of other pathologies) in the presence of persistent oligomenorrhea. Anovulatory symptoms and PCO morphology are not sufficient to make a diagnosis in adolescents, as they may be evident in normal stages in reproductive maturation (2|++OO).
Diagnosis in Perimenopause and Menopause
Although there are currently no diagnostic criteria for PCOS in perimenopausal and menopausal women, the Task Force suggests that a presumptive diagnosis of PCOS can be based upon a well-documented long term history of oligomenorrhea and hyperandrogenism during the reproductive years. The presence of PCO morphology on ultrasound would provide additional supportive evidence, although this is less likely in a menopausal woman (2|++OO).
Associated Morbidity and Evaluation
The Task Force recommends that a physical examination should document cutaneous manifestations of PCOS: terminal hair growth (see The Endocrine Society guideline Evaluation and Treatment of Hirsutism in Premenopausal Women ), acne, alopecia, acanthosis nigricans, and skin tags (1|+++O).
Women with PCOS are at increased risk of anovulation and infertility; in the absence of anovulation, the risk of infertility is uncertain. The Task Force recommends screening ovulatory status using menstrual history in all women with PCOS seeking fertility. Some women with PCOS and a eumenorrheic menstrual history may still experience anovulation and a midluteal serum progesterone may be helpful as an additional screening test (1|++OO).
The Task Force recommends excluding other causes of infertility, beyond anovulation, in couples where a woman has PCOS (1|++OO).
Because women with PCOS are at increased risk of pregnancy complications (gestational diabetes, preterm delivery, and pre-eclampsia) exacerbated by obesity, the Task Force recommends preconceptual assessment of body mass index (BMI), blood pressure, and oral glucose tolerance (1|+++O).
The evidence for intrauterine effects on development of PCOS is inconclusive. The Task Force suggests no specific interventions for prevention of PCOS in offspring of women with PCOS (2|+OOO).
Women with PCOS share many of the risk factors associated with the development of endometrial cancer including obesity, hyperinsulinism, diabetes, and abnormal uterine bleeding. However, The Task Force suggests against routine ultrasound screening for endometrial thickness in women with PCOS (2|+++O).
Increased adiposity, particularly abdominal, is associated with hyperandrogenemia and increased metabolic risk (see The Endocrine Society guideline Primary Prevention of Cardiovascular Disease and Type 2 Diabetes in Patients at Metabolic Risk ). Therefore, the Task Force recommends screening adolescents and women with PCOS for increased adiposity, by BMI calculation and measurement of waist circumference (1|+++O).
The Task Force suggests screening women and adolescents with PCOS for depression and anxiety by history and, if identified, providing appropriate referral and/or treatment (2|++OO).
Sleep-Disordered Breathing/Obstructive Sleep Apnea (OSA)
The Task Force suggests screening overweight/obese adolescents and women with PCOS for symptoms suggestive of OSA and, when identified, obtaining a definitive diagnosis using polysomnography. If OSA is diagnosed, patients should be referred for institution of appropriate treatment (2|++OO).
Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)
The Task Force suggests awareness of the possibility of NAFLD and NASH but recommends against routine screening (2|++OO).
Type 2 Diabetes Mellitus (T2DM)
The Task Force recommends the use of an oral glucose tolerance test (OGTT) (consisting of a fasting and 2-hour glucose level using a 75-g oral glucose load) to screen for impaired glucose tolerance (IGT) and T2DM in adolescents and adult women with PCOS because they are at high risk for such abnormalities (1|+++O). A hemoglobin A1c (HgbA1c) test may be considered if a patient is unable or unwilling to complete an OGTT (2|++OO). Rescreening is suggested every 3–5 years, or more frequently if clinical factors such as central adiposity, substantial weight gain, and/or symptoms of diabetes develop (2|++OO).
The Task Force recommends that adolescents and women with PCOS be screened for the following cardiovascular disease risk factors (see Table 5 in the original guideline document): family history of early cardiovascular disease, cigarette smoking, IGT/T2DM, hypertension, dyslipidemia, OSA, and obesity (especially increased abdominal adiposity) (1|++OO).
Hormonal Contraceptives (HCs): Indications and Screening
The Task Force recommends HCs (i.e., oral contraceptives, patch, or vaginal ring) as first-line management for the menstrual abnormalities and hirsutism/acne of PCOS (refer to The Endocrine Society guideline Evaluation and Treatment of Hirsutism in Premenopausal Women , recommendation 2.1.1), which treat these two problems concurrently (1|++OO).
The Task Force recommends screening for contraindications to HC use via established criteria (see Table 6 in the original guideline document and the National Guideline Clearinghouse summary of the Centers for Disease Control and Prevention's guideline U.S. medical eligibility criteria for contraceptive use, 2010) (1|++OO). For women with PCOS, the Task Force does not suggest one HC formulation over another (2|+++O).
Role of Exercise in Lifestyle Therapy
The Task Force suggests the use of exercise therapy in the management of overweight and obesity in PCOS (2|++OO). Although there are no large randomized trials of exercise in PCOS, exercise therapy, alone or in combination with dietary intervention, improves weight loss and reduces cardiovascular risk factors and diabetes risk in the general population.
Role of Weight Loss in Lifestyle Therapy
The Task Force suggests that weight loss strategies begin with calorie-restricted diets (with no evidence that one type of diet is superior) for adolescents and women with PCOS who are overweight or obese (2|++OO). Weight loss is likely beneficial for both reproductive and metabolic dysfunction in this setting. Weight loss is likely insufficient as a treatment for PCOS in normal-weight women.
Use of Metformin
The Task Force suggests against the use of metformin as a first-line treatment of cutaneous manifestations, for prevention of pregnancy complications, or for the treatment of obesity (2|++OO).
The Task Force recommends metformin in women with PCOS who have T2DM or IGT who fail lifestyle modification (1|+++O). For women with PCOS with menstrual irregularity who cannot take or do not tolerate HCs, The Task Force suggests metformin as second-line therapy (2|+++O).
Treatment of Infertility
The Task Force recommends clomiphene citrate (or comparable estrogen modulators such as letrozole) as the first-line treatment of anovulatory infertility in women with PCOS (1|+++O).
The Task Force suggests the use of metformin as an adjuvant therapy for infertility to prevent ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing in vitro fertilization (IVF) (2|++OO).
Use of Other Drugs
The Task Force recommends against the use of insulin sensitizers, such as inositols (due to lack of benefit) or thiazolidinediones (given safety concerns), for the treatment of PCOS (1|+++O).
The Task Force suggests against the use of statins for treatment of hyperandrogenism and anovulation in PCOS until additional studies demonstrate a favorable risk-benefit ratio (2|++OO). However, The Task Force suggests statins in women with PCOS who meet current indications for statin therapy (2|++OO).
Treatment of Adolescents
The Task Force suggests HCs as the first-line treatment in adolescents with suspected PCOS (if the therapeutic goal is to treat acne, hirsutism, or anovulatory symptoms, or to prevent pregnancy) (2|++OO). The Task Force suggests that lifestyle therapy (calorie-restricted diet and exercise) with the objective of weight loss should also be first-line treatment in the presence of overweight/obesity (2|++OO). The Task Force suggests metformin as a possible treatment if the goal is to treat IGT/metabolic syndrome (2|++OO). The optimal duration of HC or metformin use has not yet been determined.
For premenarchal girls with clinical and biochemical evidence of hyperandrogenism in the presence of advanced pubertal development (i.e., ≥Tanner stage IV breast development), the Task Force suggests starting HCs (2|++OO).
Quality of Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
Strength of Recommendation
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."