Polycystic Ovary Syndrome

Common endocrine disorder in reproductive-age women defined by hyperandrogenism, ovulatory dysfunction (oligo/anovulation), and often polycystic ovaries (≥2 of 3 for diagnosis).

• Most frequent cause of anovulatory infertility (up to ~10% of women). Associated with obesity, insulin resistance, and higher risks of type 2 diabetes and metabolic syndrome. Chronic anovulation leads to unopposed estrogen, increasing risk of endometrial hyperplasia or carcinoma.

• Young woman with irregular menses (oligomenorrhea/amenorrhea) and signs of hyperandrogenism (hirsutism, acne). Many patients are obese with acanthosis nigricans (insulin resistance), though lean PCOS can also occur.
• Ultrasound may show polycystic ovaries (≥12 small 2–9 mm follicles in a peripheral *string-of-pearls* pattern), but imaging is not required for diagnosis if clinical criteria are met.
• Often identified during workup for infertility due to anovulation (difficulty conceiving).

1. Rule out other causes: check β-hCG (pregnancy test), TSH, prolactin, and 17‑hydroxyprogesterone (nonclassic CAH) in any woman with oligo/amenorrhea. Test for Cushing syndrome or an androgen-secreting tumor if she has rapid-onset or severe virilization.
2. Labs: PCOS typically shows mildly elevated total testosterone (ovarian source) or DHEA-S (adrenal source); markedly high levels (>2× normal) suggest a tumor. LH:FSH ratio is often >2:1 (reflecting high LH pulse frequency), but this is not a diagnostic criterion. FSH is normal (helps exclude primary ovarian failure).
3. Pelvic ultrasound: not always necessary, but if done, look for ≥12 small follicles per ovary with the classic *string of pearls* appearance (or ovarian volume >10 mL). Only one ovary needs to meet criteria. Note that some healthy young women have polycystic-appearing ovaries without PCOS.
4. Assess metabolic status: screen for diabetes (e.g., 2-hr OGTT) and check lipid profile and blood pressure in all patients.

1. Lifestyle: Weight loss (diet & exercise) is first-line for overweight patients; even a 5–10% reduction can restore ovulation and improve metabolic health.
2. If not seeking pregnancy: Combined hormonal contraceptives (e.g., OCPs) are first-line to regulate cycles and lower androgen levels (improving acne, hirsutism). Add spironolactone for hirsutism if needed (after 6 months on OCP). Topical eflornithine or laser hair removal can help refractory facial hair.
3. Metformin: An insulin-sensitizing agent used to address metabolic issues (prediabetes, BMI >25); it often helps restore regular menses and is added for women with glucose intolerance or metabolic syndrome.
4. If seeking pregnancy: Ovulation induction is indicated. First-line is letrozole (aromatase inhibitor) due to higher ovulation and live-birth rates than clomiphene. Clomiphene (SERM) is an alternative. If these fail, use second-line therapies (exogenous gonadotropins or assisted reproduction such as IVF).
5. Prevent endometrial hyperplasia: ensure at least ~4 menses per year. If not on OCP, induce a withdrawal bleed every 1–3 months with progesterone (e.g., medroxyprogesterone) or use a progestin IUD.

• 2 out of 3 rule: Polycystic ovaries are *not* required to diagnose PCOS if hyperandrogenism and oligo/anovulation are present.
• Mnemonic HAIR-AN – a subset of PCOS with HyperAndrogenism, Insulin Resistance, Acanthosis Nigricans (severe insulin resistance phenotype).
• Think of the *string-of-pearls* sign on ultrasound – multiple small follicles line the ovarian periphery (classic PCOS finding).

• Signs of virilization (voice deepening, clitoromegaly) or very rapid onset of symptoms → evaluate for an androgen-secreting tumor (not typical PCOS).
• Prolonged amenorrhea (chronic anovulation) without treatment → risk of endometrial hyperplasia/cancer from unopposed estrogen.

1. Suspected PCOS (irregular menses + hyperandrogenism) → first exclude pregnancy, thyroid dysfunction, hyperprolactinemia, and CAH.
2. If ≥2 of 3 PCOS features (androgen excess, ovulatory dysfunction, ± polycystic ovaries) are present and other causes are ruled out → diagnose PCOS. Pelvic ultrasound can support the diagnosis if needed.
3. If patient desires fertility → lifestyle changes (weight loss) + ovulation induction (letrozole is first-line).
4. If patient does not desire pregnancy → OCPs to regulate menses and manage hyperandrogenism; add spironolactone if needed for hirsutism.
5. Address metabolic risk: regular diabetes screening (OGTT every 3–5 years), lipid panel, blood pressure; consider metformin for insulin resistance.

• Obese 25‑year‑old woman with amenorrhea, hirsutism, and acanthosis nigricans; bilateral enlarged ovaries with many small follicles on ultrasound → PCOS (hyperandrogenic anovulation).
• 28‑year‑old woman with known PCOS struggling to conceive → anovulatory infertility due to PCOS; first-line treatment is weight loss plus letrozole for ovulation induction.