Guideline sources The following summarized guidelines for the evaluation and management of polycystic ovary syndrome are prepared by our editorial team based on guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC 2023; 2018; 2017), the American Diabetes Association (ADA 2023), the Endocrine Society (ES 2020; 2013), the American College of Obstetricians and Gynecologists (ACOG 2018), the American Society for Reproductive Medicine (ASRM 2017), the American College of Endocrinology (ACE/AACE 2016), the Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS 2015), and the Royal College of Obstetricians and Gynaecologists (RCOG 2014). 1 2 3 4 5 6 7 8 9 10 11 Calculator Revised Rotterdam diagnostic cr https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 1/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway Guidelines 1. Screening and diagnosis Diagnostic criteria: As per RCOG 2014 guidelines, diagnose PCOS according to the Rotterdam consensus criteria. B As per ES 2013 guidelines: Consider diagnosing PCOS in patients meeting 2 of the following criteria, in the absence of disorders mimicking PCOS: androgen excess ovulatory dysfunction polycystic ovaries. C Consider making a presumptive diagnosis of PCOS in perimenopausal and menopausal patients with well-documented long-term history of oligomenorrhea and hyperandrogenism during the reproductive years. Look for the presence of polycystic ovarian morphology on ultrasound to provide additional supportive evidence, recognizing that this is less likely to present in menopausal patients. C Differential diagnosis: Exclude the following disorders mimicking the clinical features of PCOS before making a diagnosis of PCOS: thyroid disease hyperprolactinemia non-classic congenital adrenal hyperplasia (primarily 21-hydroxylase deficiency by serum 17-hydroxyprogesterone). B Consider obtaining a more extensive evaluation to exclude other causes in selected patients with amenorrhea and more severe phenotypes. C 2. Diagnostic investigations History and physical examination: screen for ovulatory status using menstrual history in all patients with PCOS seeking fertility. Recognize that some patients with PCOS and a eumenorrheic menstrual history may still experience anovulation, thus consider obtaining a midluteal serum progesterone level as an additional screening test. B Show 2 more Screening for congenital adrenal hyperplasia: measure 17-hydroxyprogesterone level in patients at higher risk of non-classical congenital adrenal hyperplasia and suspected PCOS. B Screening for cardiac risk: As per ES 2020 guidelines, obtain a fasting lipid panel at diagnosis to assess cardiovascular risk in patients with PCOS. B https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 2/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway As per ACOG 2018 guidelines, assess cardiovascular risks by determination of BMI, fasting lipid and lipoprotein levels, and metabolic syndrome risk factors in patients with PCOS. B As per RCOG 2014 guidelines: Recognize that conventional cardiovascular risk calculators are not validated for patients with PCOS. B Assess CVD risk in all patients with PCOS at the time of initial diagnosis by individual CVD risk factors (obesity, lack of physical activity, cigarette smoking, family history of T2DM, dyslipidemia, hypertension, impaired glucose tolerance, T2DM). B As per ES 2013 guidelines, screen for CVD risk factors, including a family history of early CVD, cigarette smoking, impaired glucose tolerance/T2DM, hypertension, dyslipidemia, obstructive sleep apnea, and obesity, especially increased abdominal adiposity, in adolescent and adult patients with PCOS. B Assess for increased adiposity by BMI calculation and measurement of waist circumference in adolescent and adult patients with PCOS. B Screening for diabetes: As per ACOG 2018 guidelines, screen for T2DM and impaired glucose tolerance with a fasting glucose level followed by a 2-hour glucose level after a 75-g glucose load in patients with PCOS. B As per RCOG 2014 guidelines: Obtain a 2-hour post 75 g oral glucose tolerance test in patients presenting with PCOS with overweight (BMI 25 kg/m ) or with normal weight (BMI < 25 kg/m ) but having additional risk factors, such as advanced age (> 40 years), personal history of gestational diabetes, or family history of T2DM. B Obtain oral glucose tolerance test annually in patients with impaired fasting glucose (fasting plasma glucose level 6.1-6.9 mmol/L) or impaired glucose tolerance (plasma glucose of 7.8 mmol/L but < 11.1 mmol/L after a 2-hour oral glucose tolerance test). B As per ES 2013 guidelines, screen for impaired glucose tolerance and T2DM in adolescent and adult patients with polycystic ovarian syndrome using an oral glucose tolerance test consisting of a fasting and 2-hour glucose level using a 75-g oral glucose load. B Show 2 more Screening for nonalcoholic fatty liver disease: do not obtain routine screening for nonalcoholic fatty liver disease and NASH in patients with PCOS, but recognize that patients are at increased risk for these conditions. D Screening for obstructive sleep apnea: As per RCOG 2014 guidelines, ask patients with PCOS (or their partners) about snoring and daytime fatigue/sleepiness, inform the possible risk of sleep apnea and offer investigation and treatment when necessary. B As per ES 2013 guidelines, consider screening or symptoms suggestive of obstructive sleep apnea and in adolescent and adult patients with PCOS and overweight/obesity, and when identified, make a definitive diagnosis using polysomnography. Refer patients with diagnosed obstructive sleep apnea for institution of appropriate treatment. C Screening for depression/anxiety: https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 3/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway As per RCOG 2014 guidelines, screen for depression and/or anxiety routinely in patients with PCOS. Obtain further assessment, provide appropriate counseling, and offer intervention by a qualified professional in patients with depression and/or anxiety. A As per ES 2013 guidelines, consider screening for depression and anxiety by history in adolescents with PCOS and, if identified, provide appropriate referral and/or treatment. C Screening for endometrial cancer: As per RCOG 2014 guidelines, recognize that oligomenorrhea or amenorrhea may predispose to endometrial hyperplasia and later carcinoma in patients with PCOS. Consider initiating progesterone to induce withdrawal bleeding at least every 3-4 months. B Show 4 more As per ES 2013 guidelines, avoid obtaining routine ultrasound screening for endometrial thickness in patients with polycystic ovarian syndrome. D 3. Medical management Hormonal contraceptives: As per ACOG 2018 guidelines, initiate combination low-dose hormonal contraceptives, frequently used for the long term, as primary treatment of menstrual disorders. B As per ES 2013 guidelines, initiate hormonal contraceptives (such as oral contraceptives, patches, or vaginal rings) as first-line therapy for menstrual abnormalities and hirsutism/acne in patients with polycystic ovarian syndrome. B Show 3 more Insulin sensitizers: As per ACOG 2018 guidelines, consider initiating insulin-sensitizing agents for improving insulin sensitivity to decrease circulating androgen levels, improve ovulation rate, and improve glucose tolerance in patients with PCOS. B As per SOGC 2018 guidelines: Recognize that metformin combined with clomiphene citrate may increase ovulation and pregnancy rates but does not significantly improve the live birth rate over that of clomiphene citrate alone. A Consider adding metformin to clomiphene citrate in patients with clomiphene resistance aged > 28 years and having visceral obesity (waist-to-hip ratio > 0.85). B As per ASRM 2017 guidelines, consider initiating metformin to increase the ovulation rate in patients with polycystic ovarian syndrome B , recognizing that metformin alone is less effective than clomiphene citrate alone for the achievement of ovulation induction, clinical pregnancy, and live birth. C As per ES 2013 guidelines, initiate metformin in patients with PCOS and T2DM or impaired glucose tolerance failed lifestyle modification. B Consider initiating metformin if the goal is to treat impaired glucose tolerance/metabolic syndrome. B Show 4 more Ovulation induction: https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 4/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway As per ACOG 2018 guidelines, consider initiating letrozole as first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate in patients with PCOS. B Show 2 more As per SOGC 2018 guidelines, consider initiating clomiphene citrate where available as first- line medical therapy for ovulation induction in patients with PCOS. Inform patients regarding the increased risk of twin pregnancy or higher order multiples with ovulation induction using clomiphene citrate. B Show 2 more As per ASRM 2017 guidelines, consider initiating letrozole as first-line therapy for ovulation induction in patients with polcystic ovary syndrome. C As per ES 2013 guidelines, initiate clomiphene citrate (or comparable estrogen modulators such as letrozole) as first-line therapy for anovulatory infertility in patients with PCOS. B Statin therapy: As per ES 2020 guidelines, avoid using lipid-lowering therapies for the treatment of hyperandrogenism or infertility in patients with PCOS. D As per RCOG 2014 guidelines, do not initiate routine lipid-lowering treatment in patients with PCOS. Prescribe only by a specialist. D As per ES 2013 guidelines: Avoid using statins for the treatment of hyperandrogenism and anovulation in patients with PCOS. D Consider initiating statins in patients with PCOS meeting current indications for statin therapy. C Weight loss medications: consider offering orlistat, metformin, or liraglutide, alone or in combination, for weight reduction or improving PCOS manifestations (including insulin resistance, glucose tolerance, dyslipidemia, hyperandrogenemia, oligomenorrhea, and anovulation) in patients with overweight or obesity and PCOS. B Management of hirsutism: consider offering eflornithine in addition to laser therapy for the treatment of hirsutism. B 4. Nonpharmacologic interventions Lifestyle modifications: As per ACOG 2018 guidelines: Advise exercising and dietary changes to reduce diabetes risk in patients with PCOS. A Advise weight loss to improve pregnancy rates, decrease hirsutism, and improve glucose tolerance and lipid levels in patients with PCOS. B As per SOGC 2018 guidelines: Consider advising weight loss through exercise and lifestyle modifications with a target of BMI < 35 kg/m and/or 5-10% of body weight if overweight for restoring ovulatory cycles and achieving pregnancy in patients with overweight and PCOS. B https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 5/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway Refer patients with morbid obesity (BMI 40 kg/m ) to qualified providers for expert advice about safe weight loss strategies and pregnancy risk in this condition. B As per AACE 2016 guidelines, advise lifestyle changes with the goal of achieving 5-15% weight loss to improve hyperandrogenism, oligomenorrhea, anovulation, insulin resistance, and hyperlipidemia in patients with overweight or obesity and PCOS. A As per RCOG 2014 guidelines, advise lifestyle changes, including diet, exercise, and weight loss, preceding and/or accompanying pharmacological treatment, for improvement of long- term outcomes in patients with PCOS. B As per ES 2013 guidelines: Consider advising calorie-restricted diets in adolescent and adult patients with PCOS with overweight or obesity. C Consider offering exercise therapy in the management of overweight and obesity in patients with polycystic ovarian syndrome. C 5. Therapeutic procedures Assisted reproductive technology: reserve IVF for patients with PCOS failed gonadotropin therapy or having other indications for IVF treatment. B 6. Surgical interventions Laparoscopic surgery: As per SOGC 2023 guidelines, consider performing laparoscopic ovarian drilling in patients with PCOS resistant to oral agents if gonadotropins are not accessible. C As per ACOG 2018 guidelines, perform laparoscopic ovarian surgery as second-line therapy if clomiphene citrate or letrozole fails to result in pregnancy. B As per SOGC 2018 guidelines, consider performing laparoscopic ovarian drilling if there are other indications for laparoscopy in patients with clomiphene- and/or letrozole-resistant PCOS, B taking into account the risks of surgery and decreased ovarian reserve. B As per RCOG 2014 guidelines, consider performing ovarian electrocautery as an alternative to ovulation induction in selected patients with anovulation, especially with normal BMI. C Bariatric surgery: As per AACE 2016 guidelines, consider offering laparoscopic Roux-en-Y gastric bypass to improve symptoms, including restoration of menses and ovulation, in selected patients with obesity and PCOS. C As per RCOG 2014 guidelines, consider offering bariatric surgery if standard weight loss strategies have failed in patients with PCOS and morbid obesity (BMI 40 kg/m or 35 kg/m with a high-risk obesity-related condition). C 7. Specific circumstances Pregnant patients: https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 6/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway As per RCOG 2014 guidelines, consider obtaining screening for gestational diabetes in patients diagnosed with PCOS before pregnancy. Obtain screening at 24-28 weeks of gestation and refer to a specialist obstetric diabetic service if abnormalities are detected. C As per ES 2013 guidelines, obtain preconceptual assessment of BMI, BP, and oral glucose tolerance because of the increased risk of pregnancy complications (gestational diabetes, preterm delivery, and preeclampsia) exacerbated by obesity in patients with PCOS. B Adolescent patients, diagnosis: As per SOGC 2017 guidelines, recognize that adolescents may present with hirsutism but the diagnosis of PCOS in young patients is controversial given that the diagnostic features of PCOS may be normal pubertal physiologic events. B As per AE-PCOS 2015 guidelines, ensure a timely diagnosis of PCOS in symptomatic adolescent patients, as it is important for the initiation of appropriate screening and treatment. A Show 6 more As per ES 2013 guidelines: Consider diagnosing polycystic ovarian syndrome in adolescent patients based on the presence of clinical and/or biochemical evidence of hyperandrogenism (after exclusion of other pathologies) in the presence of persistent oligomenorrhea. C Do not make a diagnosis of polycystic ovarian syndrome in adolescent patients based on only on anovulatory symptoms and polycystic ovarian morphology, as these findings may be evident in normal stages in reproductive maturation. D Adolescent patients (hyperandrogenemia): elicit a thorough medical history, perform physical examination and obtain appropriate laboratory assessment to provide the information necessary to exclude other disorders associated with androgen excess. A Show 6 more Adolescent patients (oligoanovulation): recognize that the majority of adolescents establish a menstrual interval of 20-45 days within the first 2 years after menarche. View menstrual intervals persistently < 20 days or > 45 days in adolescents 2 years after menarche as evidence of oligo-anovulation. B Show 2 more Adolescent patients (insulin resistance): Do not use insulin resistance and hyperinsulinemia as diagnostic criteria, although they are prevalent in adolescents at risk for PCOS. D Consider evaluating and treating potential comorbidities in patients with insulin resistance and hyperinsulinemia. C Patients with diabetes: screen for PCOS in female adolescent patients with T2DM, including laboratory studies when indicated. B Show 2 more 8. Patient education General counseling: inform patients with PCOS of the possible long-term risks to health. B https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 7/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway 9. Preventative measures Prevention in offspring: insufficient evidence to recommend any specific intervention for the prevention of PCOS in offspring of patients with PCOS. I Clinical findings Symptoms Past medical history Amenorrhea Androgenetic alopecia Anxiety Depression Hair loss Diabetes mellitus Heavy or prolonged menstrual bleeding Dyslipidemia Hypertension Hirsutism Infertility Menstrual irregularity Obesity Oligomenorrhea Obstructive sleep apnea Thinning hair Gynecologic exam Weight gain Anovulation Family history Lab findings PCOS Insulin resistance Integument exam serum LH Virilization serum prolactin serum testosterone Imaging findings Diagnostic procedures Endometrial hyperplasia Ovarian cysts Abnormal oral glucose tolerance test Polycystic ovarian morphology References 1. Kimberly Liu, Tarek Motan, Paul Claman. No. 350 Hirsutism: Evaluation and Treatment. J Obstet Gynaecol Can. 2017 Nov;39 11 1054 1068. Open 2. Royal College of Obstetricians and Gynaecologists. Long-term Consequences of Polycystic Ovary Syndrome. Green-top Guideline No. 33. RCOG. 2014 Nov. Open 3. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins Gynecology. ACOG Practice Bulletin No. 194 Polycystic Ovary Syndrome. Obstet Gynecol. 2018 Jun;131 6):e157- e171. Open 4. Practice Committee of the American Society for Reproductive Medicine. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome PCOS a guideline. Fertil Steril. 2017 Sep;108 3 426 441. Open https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 8/9 6/29/23, 11:17 PM Polycystic ovary syndrome Pathway 5. Legro RS, Arslanian SA, Ehrmann DA et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98 12 4565 92. Open 6. Selma F Witchel, Sharon Oberfield, Robert L Rosenfield et al. The Diagnosis of Polycystic Ovary Syndrome during Adolescence. Horm Res Paediatr. 2015 Apr 1. Open 7. David S Smithson, Tannys D R Vause, Anthony P Cheung. No. 362 Ovulation Induction in Polycystic Ovary Syndrome. J Obstet Gynaecol Can. 2018 Jul;40 7 978 987. Open 8. Tarek Motan, Roland Antaki, Jinglan Han et al. Guideline No. 435 Minimally Invasive Surgery in Fertility Therapy. J Obstet Gynaecol Can. 2023 Apr;45 4 273 282.e2. Open 9. W Timothy Garvey, Jeffrey I Mechanick, Elise M Brett et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3 1 203. Open 10. Connie B Newman, Michael J Blaha, Jeffrey B Boord et al. Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020 Dec 1;105 12):dgaa674. Open 11. Steven E. Kahn, Cheryl A.M. Anderson, John B. Buse et al. Standards of Care in Diabetes 2023. Diabetes Care. 2023 Jan;46 Supplement_1 S1 S291. Open 12. Teede HJ, Misso ML, Costello MF et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33 9 1602 1618. Open 13. Ritu Deswal, Vinay Narwal, Amita Dang et al. The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review. J Hum Reprod Sci. 2020 Oct-Dec;13 4 261 271. Open 14. Rotterdam ESHRE/ASRM Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome PCOS . Hum Reprod. 2004 Jan;19 1 41 7. Open 15. Helena J Teede, Marie L Misso, Michael F Costello et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33 9 1602 1618. Open https://web.pathway.md/diseases/recFqPFAD6qJjrvpe 9/9