What are the diagnostic criteria and first‑line management for polycystic ovary syndrome (PCOS) in reproductive‑age women?

Polycystic Ovary Syndrome (PCOS)

Diagnostic Criteria

Use the Rotterdam criteria: diagnose PCOS when at least two of the following three features are present—oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound—after excluding other causes of hyperandrogenism. 1, 2, 3

Clinical Assessment

• Document menstrual cycle length: cycles >35 days indicate chronic anovulation 1
• Assess androgen excess signs: acne, male-pattern balding, hirsutism distribution, and clitoromegaly 1
• Calculate BMI and waist-hip ratio as markers of metabolic risk 1
• Obtain family history of cardiovascular disease, diabetes, and PCOS 1
• Review medication use including exogenous androgens and hormonal contraceptives 1

Laboratory Testing

Total testosterone via LC-MS/MS is the single best initial biochemical marker with 74% sensitivity and 86% specificity 1, 4. Avoid direct immunoassays due to poor accuracy.

First-line hormone panel:

• Total testosterone (LC-MS/MS method) 4
• SHBG to calculate free testosterone using the Vermeulen equation (89% sensitivity, 83% specificity) 1, 4
• LH and FSH to assess ovulatory function 4

Exclusionary tests (mandatory):

• TSH to rule out thyroid disease 1, 4
• Prolactin (morning, resting level) to exclude hyperprolactinemia—women with PCOS have 3.15-fold higher risk 1, 4
• 17-hydroxyprogesterone to rule out non-classic congenital adrenal hyperplasia 1, 4

Metabolic screening (all patients):

• 2-hour oral glucose tolerance test (75-gram glucose load) to detect diabetes or impaired glucose tolerance 1, 4
• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) 1, 4

Ultrasound Criteria

Transvaginal ultrasound with ≥8 MHz transducer frequency is the optimal imaging approach in adults 1, 5.

Diagnostic thresholds for polycystic ovarian morphology:

• ≥20 follicles per ovary (2-9mm diameter) is the gold standard with 87.64% sensitivity and 93.74% specificity 1, 5
• Ovarian volume >10 mL serves as an alternative when accurate follicle counting is difficult 1, 5

Critical pitfall: Up to one-third of reproductive-aged women without PCOS have polycystic ovarian morphology on ultrasound, so ultrasound findings alone are insufficient for diagnosis 1. The presence of an IUD does not interfere with ovarian imaging 5.

Do not use ultrasound as a first-line diagnostic tool in adolescents (<8 years post-menarche or <20 years) due to poor specificity and high false-positive rates 1, 5.

Differential Diagnosis to Exclude

• Cushing's syndrome: buffalo hump, moon facies, hypertension, abdominal striae 1
• Androgen-secreting tumors: rapid onset, severe virilization, marked clitoromegaly, voice deepening 1
• Non-classic congenital adrenal hyperplasia 1
• Thyroid disease and prolactin disorders 1

First-Line Management

Lifestyle Modification (All Patients)

All women with PCOS, regardless of BMI, should receive multicomponent lifestyle intervention combining dietary modification, structured physical activity, and behavioral counseling because insulin resistance occurs independently of body weight 1. Weight loss of as little as 5% of initial weight improves metabolic and reproductive abnormalities 1.

Management Based on Primary Concern

For menstrual irregularities and hirsutism/acne (not seeking pregnancy):

Combined oral contraceptive pills are first-line therapy for long-term management of menstrual irregularities, anovulation, hirsutism, and acne 1, 2, 3. Hormonal contraceptives suppress circulating androgen levels and regulate menstrual cycles.

For infertility (attempting to conceive):

Clomiphene citrate is first-line treatment with an 80% ovulation rate and 50% conception rate 1, 2. Letrozole is an emerging alternative that may be equally or more effective 6.

For metabolic abnormalities:

Metformin is first-line medication to improve insulin sensitivity, glucose tolerance, and ovulation frequency in women with glucose intolerance or diabetes 1, 2, 3. Metformin has limited benefit for hirsutism, acne, or infertility as primary outcomes 3.

Ongoing Metabolic Surveillance

Screen all women with PCOS for cardiovascular risk factors:

• Blood pressure annually 1
• Fasting glucose or OGTT regularly (at least annually) 1
• Fasting lipid profile annually 1
• Body weight every 6-12 months 1
• Serum 25-hydroxy-vitamin D once to establish status (67-85% of PCOS patients are deficient) 1

Screen for psychological comorbidities including anxiety, depression, body-image concerns, and eating disorders, which are highly prevalent in PCOS 1, 6.

Important Clinical Pitfalls

• Do not attempt hormone testing while on hormonal contraception (including progestin-only implants like Implanon)—discontinue and wait for washout before testing 1
• Avoid thiazolidinediones due to unfavorable risk-benefit ratio 3
• Do not rely on AMH for diagnosis—lack of standardization and validated cut-offs prevent clinical use 1, 4
• Recognize that PCOS is a lifelong condition requiring continued metabolic surveillance after menopause 7