Polycystic Ovary Syndrome (PCOS)

Background

• PCOS is a heterogeneous disorder defined using various criteria, including clinical and/or biochemical hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.
• PCOS is associated with increased risk of complications, including metabolic complications (such as hyperinsulinemia, obesity, and dyslipidemia), pregnancy complications, mental health complications, endometrial cancer, and possibly obstructive sleep disorder.
• The etiology of PCOS is unclear, although it is thought that PCOS is the result of a combination of genetic and epigenetic factors, hypothalamic and ovarian dysfunction, excess exposure to androgen, insulin resistance, and mechanisms related to excess adiposity.

Evaluation

• Obtain a detailed history and physical to identify components of PCOS (such as irregular menstrual cycles and clinical hyperandrogenism) and to assess for complications associated with PCOS.
• Diagnostic testing in a patient with suspected PCOS depends on clinical presentation and the gynecological age of the patient.
  • If the patient presents with both evidence of clinical hyperandrogenism and menstrual history suggesting ovulatory dysfunction and other diagnoses have been excluded, then the patient meets criteria for PCOS.
  • If the patient presents without evidence of clinical hyperandrogenism, but has menstrual history suggesting ovulatory dysfunction:
    • Evaluate for biochemical hyperandrogenism.
      • Free testosterone assessed using equilibrium techniques is the preferred method for evaluating for biochemical hyperandrogenism.
      • If limited access to high-quality free testosterone assays, assess for biochemical hyperandrogenism with free androgen index, calculated free testosterone, or calculated bioavailable testosterone (Strong recommendation).
    • Assess for polycystic ovaries on ultrasound if patient has no evidence of biochemical hyperandrogenism and is ≥ 8 years post-menarche (gynecological age ≥ 8 years).
  • If the patient presents with evidence of only (clinical or biochemical) hyperandrogenism or irregular menstrual cycles:
    • Assess for polycystic ovaries on ultrasound if patient is ≥ 8 years post-menarche (gynecological age ≥ 8 years).
    • Ultrasound is not recommended in patients < 8 years post-menarche (gynecological age of < 8 years) for diagnosis of PCOS as multifollicular ovaries are common at this stage of life (Strong recommendation).
  • In those with regular menstrual cycles who need further assessment for ovulatory dysfunction:
    • Ovulatory dysfunction can be confirmed by performing a midluteal (days 21-22) serum progesterone test to assess for anovulation.
    • Perform ultrasound monitoring of ovarian activity along with assessment of serum progesterone to provide additional information on timing of ovulation and ovulatory function (Strong recommendation).
• Prior to making a diagnosis of PCOS, perform testing to exclude other conditions that mimic PCOS.
• After PCOS diagnosis:
  • Assess all patients with PCOS for presence of individual cardiometabolic risk factors.
    • Assess blood pressure annually or more frequently based on global cardiovascular risk (Strong recommendation).
    • Assess weight at least every 6-12 months to monitor for weight changes and excess weight (Strong recommendation).
    • Calculate body mass index (BMI) and use ethnic and adolescent ranges to evaluate for overweight and obesity (Strong recommendation).
    • Ideally measure waist circumference and use ethnic and adolescent ranges to evaluate for abdominal obesity (Strong recommendation).
  • Assess all patients with PCOS for anxiety and depression symptoms. If anxiety and depression symptoms are present, further assessment and/or referral for assessment is required (Strong recommendation).

Management

• Lifestyle modification including changes to diet and/or physical activity, is the first-line treatment for long-term outcome improvement preceding and/or accompanying pharmacological treatment in patients with PCOS (Strong recommendation).
• Management of clinical hyperandrogenism (such as hirsutism, acne, and androgenic alopecia) in patients with PCOS varies by whether or not the patient is seeking fertility.
  • In patients who are not seeking fertility:
    • Management of hirsutism:
      • First-line pharmacological therapy is with combined oral contraceptives and/or antiandrogen therapy.
        • For most patients with hirsutism not seeking fertility, consider combined oral contraceptives as initial therapy to treat patient-important hirsutism (Weak recommendation).
        • For patients with long-acting reversible contraception, permanent sterilization, or not sexually active, consider either combined oral contraceptives or antiandrogen therapy as initial therapy (Weak recommendation), with choice based on efficacy, side effect profile, and patient preferences.
        • Consider combination therapy (combined oral contraceptives plus antiandrogen therapy) if:
          • severe hirsutism results in emotional distress (Weak recommendation)
          • hirsutism persists for ≥ 6 months (Weak recommendation)
          • previous use of combined oral contraceptives did not lead to a sufficient improvement in hirsutism (Weak recommendation)
        • Consider a ≥ 6 month trial for all pharmacological therapies before changing dose, switching medication, or adding another medication (Weak recommendation), as it may take 6 months to achieve clinically significant improvement due to growth cycle of terminal hair.
      • If additional cosmetic benefits are desired despite the use of pharmacological therapy, consider permanent hair removal methods such as electrolysis or light-based therapies (Weak recommendation). These can be used as monotherapy in mild cases or as adjunctive therapy in more severe cases.
    • Management of acne:
      • Combined oral contraceptives are recommended as first-line treatment
        • in adults with PCOS (Strong recommendation)
        • in adolescents with PCOS (Weak recommendation)
      • No particular combined oral contraceptive is recommended over another for patients with PCOS; however, risk-benefit ratios might differ among preparations and type of progestin in combined oral contraceptives.
      • Consider topical creams (such as antibiotic cream, benzoyl peroxide, tretinoin, or adapalene) in addition to combined oral contraceptives.
      • Consider spironolactone as second-line therapy. Spironolactone should only be prescribed in combination with effective contraception due to risk of teratogenicity (risk of feminization of male fetus).
    • Management of androgenic alopecia:
      • First-line treatment is with topical minoxidil plus antiandrogen therapy (in combination with effective contraception).
      • Alternative treatments for androgenic alopecia may include:
        • low-level laser light therapy
        • scalp injections with platelet-rich plasma
        • hair transplantation
  • In patients who are seeking fertility:
    • For management of hirsutism, consider cosmetic hair removal strategies. This includes temporary hair removal procedures, such as plucking, waxing, and shaving, or permanent hair removal via electrolysis and light-based therapies.
    • For management of acne, consider topical creams such as antibiotic creams or benzoyl peroxide.
• Management of irregular menstrual cycles in patients not seeking fertility:
  • Combined oral contraceptives are recommended as first-line pharmacological therapy
    • in adults with PCOS (Strong recommendation)
    • in adolescents with PCOS (Weak recommendation)
  • Other first-line pharmacological therapy options include oral progestins or levonorgestrel-releasing intrauterine system.
  • Consider metformin as second-line pharmacological therapy for management of irregular menstrual cycles.
• For adults with anovulatory infertility, treatment options vary by guideline group and local availability, but typical options include letrozole, clomiphene citrate, and metformin.