Polycystic ovary syndrome

Introduction
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. It is a heterogeneous condition with reproductive, metabolic, and psychological consequences. PCOS is a major cause of infertility due to ovulatory dysfunction and is associated with increased risk of type 2 diabetes, metabolic syndrome, and cardiovascular disease.

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Epidemiology

• Affects 6–12% of women of reproductive age globally, depending on diagnostic criteria used.

• Often manifests during adolescence but can present at any reproductive age.

• Familial clustering suggests a genetic predisposition, although environmental and lifestyle factors play a significant role.

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Etiology and Pathophysiology
PCOS is multifactorial, involving genetic, hormonal, and environmental influences:

• Hyperandrogenism: Increased ovarian and/or adrenal androgen production.

• Insulin resistance: Common in PCOS, exacerbates hyperandrogenism by stimulating ovarian theca cells and reducing hepatic sex hormone-binding globulin (SHBG) synthesis.

• Hypothalamic-pituitary-ovarian (HPO) axis dysregulation: Increased gonadotropin-releasing hormone (GnRH) pulsatility → elevated LH secretion → stimulation of androgen production.

• Polycystic ovarian morphology: Increased number of small antral follicles arrested in development due to hormonal imbalance.

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Diagnostic Criteria
The Rotterdam criteria (2003) are most widely used—diagnosis requires two of the following three:

1. Oligo- or anovulation (infrequent or absent menstrual periods).

2. Clinical and/or biochemical signs of hyperandrogenism (hirsutism, acne, elevated serum androgens).

3. Polycystic ovaries on ultrasound (≥12 follicles 2–9 mm in diameter or ovarian volume >10 mL in at least one ovary).

Other causes of hyperandrogenism and anovulation must be excluded (e.g., congenital adrenal hyperplasia, androgen-secreting tumors, Cushing’s syndrome, thyroid disorders, hyperprolactinemia).

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Clinical Features

Reproductive

• Irregular menstrual cycles (oligomenorrhea, amenorrhea).

• Infertility due to chronic anovulation.

Androgenic

• Hirsutism (excess terminal hair growth in male-pattern distribution).

• Acne, oily skin.

• Androgenic alopecia (male-pattern hair loss).

Metabolic

• Central obesity.

• Insulin resistance and hyperinsulinemia.

• Increased risk of type 2 diabetes, dyslipidemia, and metabolic syndrome.

Psychological

• Depression, anxiety.

• Body image concerns.

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Investigations

Laboratory tests (to assess and exclude other causes):

• Total and free testosterone (often mildly elevated).

• DHEA-S (if markedly elevated, consider adrenal source).

• LH and FSH (LH:FSH ratio often >2:1 in PCOS but not diagnostic).

• Prolactin, TSH (to exclude thyroid and pituitary causes).

• 17-hydroxyprogesterone (to exclude late-onset congenital adrenal hyperplasia).

• Fasting glucose, oral glucose tolerance test (OGTT).

• Lipid profile.

Imaging

• Pelvic ultrasound (transvaginal preferred in non-virginal women): multiple small peripheral follicles and increased ovarian stroma.

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Management
Treatment is individualized, addressing patient priorities (e.g., menstrual regulation, fertility, cosmetic concerns, metabolic health).

1. Lifestyle Modification (First-line in overweight/obese women)

• Calorie-controlled diet and regular exercise.

• Aim for 5–10% weight loss to improve menstrual regularity, ovulation, insulin sensitivity, and metabolic profile.

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2. Menstrual Regulation and Endometrial Protection

• Combined oral contraceptives (COCs):

  • Provide cycle control, reduce androgen production, and increase SHBG.

  • Example: Ethinylestradiol 20–35 mcg + levonorgestrel/desogestrel/drospirenone — 1 tablet daily for 21 days, then 7-day pill-free or placebo interval.

• Progestin therapy (for those who cannot take estrogen):

  • Medroxyprogesterone acetate 10 mg orally daily for 10–14 days every 1–3 months to induce withdrawal bleeding and prevent endometrial hyperplasia.

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3. Hyperandrogenism (Hirsutism, Acne)

• COCs (as above).

• Antiandrogens (only with reliable contraception due to teratogenicity):

  • Spironolactone: 50–100 mg orally twice daily; monitor potassium.

  • Cyproterone acetate: 25–50 mg daily (cyclic or continuous).

  • Finasteride: 2.5–5 mg orally daily.

• Topical: Eflornithine 13.9% cream applied to affected facial areas twice daily for hirsutism.

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4. Insulin Resistance and Metabolic Features

• Metformin: 500 mg orally once or twice daily, titrated to 1,500–2,000 mg/day as tolerated; improves insulin sensitivity, menstrual regularity, and ovulation rates.

• Lifestyle modification remains essential alongside pharmacotherapy.

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5. Infertility Management

• First-line ovulation induction:

  • Letrozole (aromatase inhibitor): 2.5–5 mg orally daily for 5 days starting on day 3–5 of cycle.

• Alternative: Clomifene citrate 50–150 mg orally daily for 5 days (monitor for multiple pregnancy risk).

• Adjunct: Metformin in women with insulin resistance, especially if clomifene-resistant.

• Second-line: Gonadotropins (FSH injections) with careful monitoring to avoid ovarian hyperstimulation syndrome (OHSS).

• Third-line: Laparoscopic ovarian drilling in selected cases.

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6. Management of Long-term Risks

• Regular screening for glucose intolerance and dyslipidemia.

• Blood pressure monitoring.

• Counseling on cardiovascular risk.

• Weight management and physical activity promotion.

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Prognosis
PCOS is a chronic condition, but symptoms and risks can be mitigated with lifestyle modification and appropriate medical management. Fertility can often be restored, and metabolic and cosmetic concerns can be improved significantly. Long-term follow-up is recommended due to the increased lifetime risk of type 2 diabetes, cardiovascular disease, and endometrial cancer.