Polycystic Ovary Syndrome (PCOS) - Management

Diagnosis First: Rotterdam Criteria

1. Ovarian dysfunction - oligomenorrhea or amenorrhea
2. Hyperandrogenism (HA) - clinical (hirsutism, acne, alopecia) or biochemical (elevated bioavailable testosterone)
3. Polycystic ovarian (PCO) morphology on ultrasound - ≥20 follicles in either ovary measuring 2-9 mm and/or ovarian volume >10 mL

• Hyperprolactinemia
• Nonclassic congenital adrenal hyperplasia (check basal follicular-phase 17-OHP)
• Cushing's syndrome
• Androgen-secreting neoplasm
• Thyroid disorder

Diagnostic algorithm for PCOS - Berek & Novak's Gynecology

Initial Assessment (All Women with PCOS)

• 30-45% of obese PCOS women have glucose intolerance or T2DM
• Dyslipidemia is present in up to 70% of PCOS women (decreased HDL, elevated triglycerides, altered LDL quality)
• Acanthosis nigricans is a clinical marker of insulin resistance (IR)

1. Lifestyle Management (First-Line for All)

• Structured exercise + dietary modification
• Targets: reduce central adiposity, improve IR, lower androgen levels
• A 2025 systematic review (PMID 39861440) confirms lifestyle interventions improve hormonal balance, insulin sensitivity, and menstrual regularity

2. Management Based on Presenting Goal

A. Menstrual Regulation / Endometrial Protection (Not Seeking Pregnancy)

• Regulate cycles and reduce androgens by increasing SHBG, reducing LH, and inhibiting 5α-reductase
• Prefer formulations with newer progestins (desogestrel, gestodene, norgestimate, drospirenone) which have minimal androgenic activity
• Avoid norgestrel, norethindrone - these are androgen-dominant progestins
• Use lowest effective estrogen dose, either cyclic or continuous
• Alternatively: medroxyprogesterone acetate (MPA) 10 mg or progesterone 200 mg for 10-14 days every ≥3 months, or levonorgestrel IUD

Harrison's 22e notes: COCs are first-line for women not attempting pregnancy; metformin alone is NOT recommended for endometrial protection.

B. Hyperandrogenism (Hirsutism / Acne)

• COCs - initial therapy; allow 6 months before assessing response
• If inadequate response after 6 months, add antiandrogens:
  • Spironolactone (50-200 mg/day) - most commonly used; blocks androgen receptors and inhibits 5α-reductase. Requires contraception (teratogenic)
  • Flutamide - non-steroidal antiandrogen; liver toxicity risk limits use
  • Finasteride (5α-reductase inhibitor) - less effective than spironolactone
• GnRH agonists (e.g., leuprolide) - reserved for severe/refractory hirsutism; suppress ovarian androgens to castrate levels. Add "add-back" estrogen/OC to prevent bone loss
• Dexamethasone - for adrenal or mixed adrenal/ovarian hyperandrogenism; very low doses (0.25 mg at bedtime)
• Physical methods (laser, electrolysis) - adjunctive cosmetic treatment; do not treat the underlying cause

C. Metabolic / Insulin Resistance Management

• Consider in overweight/obese women for prevention of cardiometabolic risk factors
• Useful adjunct with diet and exercise; indicated for impaired glucose tolerance or T2DM
• NOT recommended as monotherapy for hyperandrogenism, endometrial protection, or infertility

• A 2024 meta-analysis (PMID 39178623) shows GLP-1 agonists (e.g., semaglutide) promote significant weight loss and improve hormonal parameters in obese PCOS women - increasingly used in this population

D. Fertility / Ovulation Induction

1. Letrozole (aromatase inhibitor) - first-line for ovulation induction; superior to clomiphene for live birth rates in PCOS
2. Clomiphene citrate (SERM) - second-line; with or without metformin
3. Injectable gonadotropins - used judiciously by specialists; risk of ovarian hyperstimulation syndrome (OHSS) is elevated in PCOS - target monofollicular growth
4. Laparoscopic ovarian drilling (LOD) - surgical option for clomiphene-resistant anovulation; can restore ovulation via reduction of ovarian androgen production
5. IVF - for treatment failures or where other indications coexist

3. Special Populations

Adolescents

• Diagnosis should require both persistent anovulation AND clinical/biochemical HA (PCO morphology alone is insufficient in adolescents)
• Distinguish from normal pubertal development

Pregnancy

• PCOS and insulin resistance worsen outcomes; metformin may be continued in some cases per specialist guidance
• Screen for gestational diabetes early

Mental Health

• Depression and anxiety occur at higher rates in PCOS - screen routinely with PHQ-2 and refer as needed

Summary Table: Management by Goal

• Berek & Novak's Gynecology, Chapter 35 (pp. 1919-1936)
• Harrison's Principles of Internal Medicine 22E, Chapter 405
• Recent evidence: lifestyle interventions (PMID 39861440, 2025), GLP-1 agonists (PMID 39178623, 2024), pregnancy outcomes (PMID 38965226, 2024)