What are the diagnostic criteria and treatment options for a woman of reproductive age with suspected Polycystic Ovary Syndrome (PCOS)?

Diagnosis of Polycystic Ovary Syndrome (PCOS)

PCOS is diagnosed when at least two of three criteria are present: oligo- or anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound—after excluding other causes of androgen excess. 1, 2

Diagnostic Criteria (Rotterdam Criteria)

You need at least 2 of the following 3 features to diagnose PCOS:

1. Oligo- or Anovulation

• Menstrual cycle length >35 days suggests chronic anovulation 1
• Cycles slightly longer than normal (32-35 days) or slightly irregular require assessment for ovulatory dysfunction 3
• Persistent oligomenorrhea 2-3 years beyond menarche predicts ongoing menstrual irregularities 3

2. Clinical and/or Biochemical Hyperandrogenism

Clinical signs to assess:

• Hirsutism (develops gradually, intensifies with weight gain) 1, 3
• Acne (severe or resistant to treatment including isotretinoin) 1, 3
• Male-pattern hair loss (vertex, crown, diffuse pattern, or bitemporal with frontal hairline loss in severe cases) 1, 3
• Clitoromegaly (suggests rapid-onset virilizing tumor if present) 1

Biochemical testing (first-line):

• Total testosterone via LC-MS/MS is the single best initial marker with 74% sensitivity and 86% specificity 4
• Calculated free testosterone has the highest sensitivity at 89% with 83% specificity 1, 4
• LC-MS/MS shows superior specificity (92%) compared to direct immunoassays (78%) 2, 4

Second-line androgen testing (if testosterone normal but clinical suspicion high):

• Androstenedione (75% sensitivity, 71% specificity) 4
• DHEAS (75% sensitivity, 67% specificity) 4

3. Polycystic Ovarian Morphology on Ultrasound

Gold standard criteria:

• ≥20 follicles per ovary (2-9mm diameter) with 87.64% sensitivity and 93.74% specificity 1, 2
• Ovarian volume >10 mL as alternative when accurate follicle counting is difficult 1, 2
• Use transvaginal ultrasound with ≥8 MHz transducer frequency in adults 1, 2

Critical caveat: Do NOT use ultrasound in adolescents <8 years post-menarche or <20 years old due to poor specificity and high false-positive rates 1, 2

Essential Exclusionary Testing

Before confirming PCOS, rule out these conditions:

Mandatory laboratory tests:

• TSH to exclude thyroid disease 2, 4
• Prolactin (morning resting levels) to exclude hyperprolactinemia 2, 4
• 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 2

Consider if clinically indicated:

• Dexamethasone suppression test if Cushing's syndrome suspected (buffalo hump, moon facies, hypertension, abdominal striae) 1, 2
• Rapid onset and severe hyperandrogenism suggests androgen-secreting tumor 1, 2

Metabolic Screening (Mandatory for All PCOS Patients)

All women with PCOS require screening regardless of BMI:

• 2-hour oral glucose tolerance test (75g glucose load) to detect type 2 diabetes and glucose intolerance 2, 4
• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) 2, 4
• BMI calculation 1, 2
• Waist-hip ratio (>0.9 indicates central obesity) 1, 4
• Look for acanthosis nigricans (neck, axillae, under breasts, vulva) indicating insulin resistance 2

Important Clinical Pitfalls

When ultrasound is NOT needed: If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for diagnosis (though it identifies the complete phenotype) 4

AMH is NOT recommended: Do not use AMH levels as an alternative for detecting polycystic ovarian morphology or as a single diagnostic test due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 1, 4

Normal labs don't exclude PCOS: Total testosterone is abnormal in only 70% of women with confirmed PCOS, and LH/FSH ratio >2 is abnormal in only 35-44% of cases 4. Clinical assessment with menstrual pattern, physical signs of hyperandrogenism, and ultrasound morphology can establish diagnosis even when laboratory tests return normal 4

Hormonal contraception interferes with testing: Progestin-only implants and combined oral contraceptives suppress the hypothalamic-pituitary-ovarian axis, making hormone levels unreliable. Remove or allow expiration before testing 1

Treatment Options

First-Line: Lifestyle Modification

• Weight loss of as little as 5% of initial weight improves metabolic and reproductive abnormalities 1, 5
• Regular exercise and weight control measures should be implemented before drug therapy 1

Menstrual Irregularity Management

• Combination oral contraceptive pills are first-line therapy for long-term management of menstrual irregularities and anovulation 1, 5
• Medroxyprogesterone acetate (depot or intermittent oral) to suppress circulating androgen levels 1

Infertility Treatment

• Clomiphene citrate is first-line treatment for women attempting to conceive, with 80% ovulation rate and 50% conception rate 1, 6
• Start with 50 mg daily for 5 days; increase to 100 mg daily for 5 days if no ovulation occurs 6
• Low-dose gonadotropin therapy for those who fail clomiphene 1
• Metformin improves insulin sensitivity, glucose tolerance, and ovulation frequency 1

Hirsutism Management

• Oral contraceptives as first-line therapy 1
• Combination of anti-androgen (spironolactone, cyproterone acetate, flutamide, or finasteride) with ovarian suppression agent for better efficacy 1, 3
• Mechanical hair removal, electrolysis, and laser vaporization for cosmetic management 1

Long-Term Monitoring

• Regular screening for cardiovascular risk factors 1
• Monitor for type 2 diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease 7
• Screen for sleep apnea and mental health issues (depression, eating disorders) 7