Reproductive · PANCE / PANRE

Polycystic Ovary Syndrome (PCOS)

Hyperandrogenism + ovulatory dysfunction + polycystic ovarian morphology; insulin resistance is the common thread.

Also known as: PCOS, Stein-Leventhal syndrome, polycystic ovaries, functional ovarian hyperandrogenism

Overview

Heterogeneous endocrine disorder of reproductive-age women defined (Rotterdam 2003) by 2 of 3 criteria: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound — after exclusion of other causes.

Epidemiology

Affects 8-13% of reproductive-age women worldwide; most common endocrinopathy in this group and a leading cause of anovulatory infertility.

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Risk factors

Family history of PCOS or type 2 diabetes
Obesity, particularly central adiposity
Premature adrenarche, low birth weight
Insulin resistance, metabolic syndrome

Pathophysiology

Insulin resistance with compensatory hyperinsulinemia augments LH-driven ovarian theca cell androgen production and suppresses hepatic SHBG, increasing free testosterone. Elevated LH:FSH ratio impairs follicular maturation, producing arrested antral follicles (the 'polycystic' appearance) and anovulation. Unopposed estrogen exposure raises endometrial cancer risk.

Clinical presentation

Symptoms

Oligomenorrhea or amenorrhea, typically since menarche
Hirsutism (upper lip, chin, chest, abdomen, back)
Acne, androgenic alopecia
Infertility, recurrent pregnancy loss
Weight gain, difficulty losing weight

Signs / physical exam

BMI often elevated; central adiposity
Acanthosis nigricans (insulin resistance marker)
Modified Ferriman-Gallwey score ≥4-8 (population-dependent)
Acne, male-pattern hair thinning

Classic findings

Young woman with irregular menses, hirsutism, acne, and obesity; ultrasound with ≥20 follicles per ovary or ovarian volume >10 mL.

Differential diagnosis

Thyroid disease — Menstrual irregularity from hypo- or hyperthyroidism; check TSH
Hyperprolactinemia — Galactorrhea, amenorrhea; prolactin elevated; consider pituitary adenoma
Non-classic congenital adrenal hyperplasia (21-hydroxylase deficiency) — Hirsutism with elevated 17-hydroxyprogesterone (early morning, follicular phase >200 ng/dL warrants ACTH stim)
Cushing syndrome — Central obesity, striae, easy bruising, proximal weakness; abnormal dexamethasone suppression or 24-h urine cortisol
Androgen-secreting tumor (ovarian or adrenal) — Rapid virilization, total testosterone >150-200 ng/dL or DHEAS markedly elevated; imaging
Primary ovarian insufficiency — Amenorrhea with elevated FSH and low estradiol
Hypothalamic amenorrhea — Low BMI, excessive exercise, stress; low FSH/LH and low estradiol
Idiopathic hirsutism — Regular menses, normal androgens

Diagnostic workup

Diagnostic criteria

Rotterdam criteria (2 of 3): (1) oligo- or anovulation, (2) clinical or biochemical hyperandrogenism, (3) polycystic ovarian morphology on ultrasound — AFTER excluding thyroid disease, hyperprolactinemia, NCCAH, Cushing, and androgen-secreting tumors.

Labs

Total and free testosterone, SHBG, DHEAS
TSH, prolactin, 17-hydroxyprogesterone (early-morning follicular)
Fasting glucose and 2-h OGTT, A1c, lipid panel
If amenorrhea: FSH, LH, estradiol, urine hCG
Endometrial biopsy if prolonged amenorrhea or abnormal bleeding (rule out hyperplasia)

Imaging

Transvaginal pelvic ultrasound: ≥20 follicles per ovary (2-9 mm) and/or ovarian volume >10 mL (per 2018 international guideline)
Ultrasound morphology is NOT required if irregular menses + hyperandrogenism present; also not used in adolescents within 8 years of menarche

Diagnostic algorithm

Domain	Finding	Workup
Ovulatory dysfunction	Oligomenorrhea (<8 cycles/yr) or amenorrhea	Cycle history; progesterone if uncertain
Hyperandrogenism (clinical)	Hirsutism, acne, androgenic alopecia	Modified Ferriman-Gallwey score
Hyperandrogenism (biochemical)	Elevated total/free testosterone, DHEAS	Morning total + free testosterone, SHBG
Polycystic morphology	≥20 follicles/ovary or volume >10 mL	Transvaginal ultrasound (not in adolescents)
Exclude mimics	Normal TSH, prolactin, 17-OHP, cortisol	TSH, prolactin, 17-OHP, dexamethasone suppression if indicated

Rotterdam criteria for PCOS — 2 of 3 features required after exclusion of mimics.

Treatment

First-line

Lifestyle modification: 5-10% weight loss restores ovulation in many; Mediterranean-style diet, 150 min/wk moderate exercise
Combined oral contraceptive (COCP) — ethinyl estradiol/levonorgestrel, drospirenone, or norethindrone — for menstrual regulation, hirsutism, acne; protects endometrium
Metformin — improves insulin sensitivity, modest weight loss, restores ovulation in some; first-line for impaired glucose tolerance

Infertility / ovulation induction

Letrozole — first-line (superior live birth vs clomiphene in PCOS per PPCOS II trial)
Clomiphene citrate — second-line
Gonadotropins or IVF if oral agents fail

Hirsutism

COCP × 6 months before judging response
Add spironolactone 50-200 mg/day (anti-androgen) — must be paired with reliable contraception (teratogen)
Eflornithine cream for facial hair; mechanical/laser hair removal as adjunct

Endometrial protection if COCP contraindicated

Cyclic progestin (medroxyprogesterone 5-10 mg × 10-14 days every 1-3 months)
Levonorgestrel IUD

Second-line / adjunct

GLP-1 receptor agonists (semaglutide, liraglutide) for weight loss in obese patients
Bariatric surgery for BMI ≥35 with comorbidities
Inositol supplementation — modest evidence, low risk

Complications

Type 2 diabetes (4x risk), metabolic syndrome, NAFLD
Endometrial hyperplasia and endometrial carcinoma (from chronic unopposed estrogen)
Infertility, increased miscarriage rate, gestational diabetes, preeclampsia
Obstructive sleep apnea, depression and anxiety
Possible increased risk of cardiovascular disease

PANCE pearls

Letrozole has replaced clomiphene as first-line for ovulation induction in PCOS-associated infertility.
Spironolactone is teratogenic (feminization of male fetus) — always combine with effective contraception.
Adolescent diagnosis requires BOTH hyperandrogenism AND persistent oligomenorrhea (≥2 years post-menarche); ultrasound morphology should not be used.
Screen all PCOS patients for diabetes with a 2-h OGTT (more sensitive than A1c or fasting glucose alone) every 1-3 years.
Prolonged amenorrhea (>3 months) warrants either withdrawal bleed induction with progestin or endometrial sampling.

References

International PCOS Guideline 2023 — 2023 International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (Teede et al., Fertil Steril 2023)
ACOG PB 194 — ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome (Obstet Gynecol 2018)
PPCOS II — Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome (Legro et al., NEJM 2014)

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