Characterized by hyperandrogenism, oligoovulation/anovulation, and/or the presence of polycystic ovaries

Epidemiology

• Prevalence: 6�?2% of women in their reproductive years in the US

Etiology

Pathophysiology

• Strong association with obesity �?�?in peripheral estrogen synthesis from adipose tissue and �?in peripheral sensitivity to insulin
  • Estrogen is also produced in other aromatase-containing tissues: Fatty tissue, Placenta
• Reduced insulin sensitivity (peripheral insulin resistance) and the consequent hyperinsulinemia result in: ↑LH:FSH
  • Epidermal hyperplasia and hyperpigmentation (acanthosis nigricans)
  • �?Androgen production in ovarian theca interna cells �?imbalance between androgen precursors and the resulting estrogen produced in granulosa cells
    • �?LH secretion disrupts the LH/FSH balance �?impaired follicle maturation �?unruptured follicles and anovulation/oligoovulation �?cyst formation and infertility
    • �?Androgen precursor release and �?estrogen production in adipose tissue
  • Inhibition of SHBG in the liver �?�?free androgens and estrogens
    • SHBG production in the liver is suppressed by androgen and insulin and stimulated by estrogen and hyperthyroidism.
    • �?Unopposed estrogen (lack of progesterone) during anovulatory cycles �?endometrial hyperplasia �?�?risk of endometrial carcinoma

Clinical features

Onset of symptoms typically occurs during adolescence.

• Menstrual irregularities
  • Primary or secondary amenorrhea
  • Oligomenorrhea
  • Menorrhagia
  • Infertility or difficulties conceiving
• Insulin resistance and associated conditions
  • Metabolic syndrome (especially obesity) �?�?risk of sleep apnea
  • Nonalcoholic fatty liver disease
• Skin conditions
  • Hirsutism
    • A condition of excessive male pattern hair growth in women (e.g., on the chin, above the upper lip, and around the umbilicus) that is most commonly idiopathic but associated with excess androgen in 10% of cases.
  • Androgenic alopecia
  • Acne vulgaris
  • Oily skin
  • Acanthosis nigricans
• Psychiatric conditions
• Malignancy (increased risk before menopause): Endometrial cancer
  

Diagnostics

Treatment

• Target BMI < 25 kg/m² (can reduce estrone production in the adipose tissue)

Patients not planning to conceive

For patients who do not wish to conceive, the therapeutic goals are to control menstrual irregularities and hyperandrogenism, treat comorbidities, and improve quality of life.

• Combined oral contraceptives (COCs)
  • Indication: first-line treatment for hyperandrogenism and/or menstrual cycle abnormalities
    • Additional benefits
      • �?Endometrial hyperplasia �?�?risk of endometrial carcinoma
      • �?Menstrual bleeding
      • �?Acne
      • Treatment of hirsutism
        • COCs increase the production of SHBG, which binds excess androgen.
• Metformin: improves menstrual irregularities, metabolic outcomes, and weight (especially when combined with lifestyle modifications)

Patients planning to conceive

Management of comorbidities (e.g., weight loss for overweight or obese patients) and induction of ovulation.

• Letrozole (off-label): first-line therapy for ovulation induction
  • An aromatase inhibitor
  • Improves pregnancy and live birth rates in patients with anovulatory infertility with no other causes
  • Mechanism of action: aromatase inhibition reduces estrogen production, stimulating FSH secretion and inducing ovulation
• Clomiphene: alternative to letrozole
• Exogenous gonadotropins: The low-dose regimen is the second-line treatment for ovulation induction.
  • Agents: exogenous FSH and human menopausal gonadotropin
• Metformin
  • Can be used as second-line monotherapy for fertility treatment.
  • Combination with clomiphene may increase pregnancy rates, especially in obese women.