What is the recommended workup and treatment for a female patient with suspected Polycystic Ovary Syndrome (PCOS)?

PCOS Workup and Treatment

Diagnostic Workup

The diagnosis of PCOS requires at least two of three Rotterdam criteria: hyperandrogenism (clinical or biochemical), ovulatory dysfunction (oligo/anovulation), and polycystic ovarian morphology on ultrasound, after excluding other causes of androgen excess. 1

Essential Laboratory Tests

Hormonal Assessment:

• Measure total or free testosterone using mass spectrometry (LC-MS/MS) as first-line, which has 92% specificity versus 78% for direct immunoassays 1
• Check LH and FSH levels to assess gonadotropin patterns 2
• Measure 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1
• Check TSH to exclude thyroid disease causing menstrual irregularity 1
• Measure prolactin to exclude hyperprolactinemia 1

Metabolic Screening (mandatory for ALL patients regardless of BMI):

• Perform 2-hour oral glucose tolerance test (75g) to detect type 2 diabetes and glucose intolerance—insulin resistance occurs independently of body weight in PCOS 1
• Obtain fasting lipid profile 2
• Calculate BMI and waist-to-hip ratio to assess central obesity and metabolic risk 2, 1

Physical Examination Findings

• Look for acanthosis nigricans on neck, axillae, under breasts, and vulva, which indicates underlying insulin resistance 1
• Assess for clinical hyperandrogenism: hirsutism, acne, male-pattern baldness 2
• Consider dexamethasone suppression test if Cushing's syndrome is suspected 1

Ultrasound Criteria

• Transvaginal ultrasound is preferred if sexually active and acceptable to patient, using 8 MHz frequency transducers 1
• Polycystic ovarian morphology is defined as ≥20 follicles per ovary (2-9mm diameter) and/or ovarian volume ≥10 mL, with no corpus luteum, cyst, or dominant follicle present 1
• Do NOT use ultrasound for diagnosis in adolescents with gynecological age <8 years post-menarche due to physiologically normal multifollicular ovaries at this stage 1
• In patients with irregular cycles AND hyperandrogenism, ultrasound is not necessary for diagnosis but identifies the complete PCOS phenotype 1

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Treatment Algorithm

Step 1: Lifestyle Modification (MANDATORY FIRST-LINE FOR ALL PATIENTS)

Lifestyle modification targeting 5-10% weight loss through diet and exercise is the foundational first-line treatment for all women with PCOS, improving metabolic, reproductive, and psychological outcomes. 2

Dietary Intervention:

• Target energy deficit of 500-750 kcal/day, with total intake of 1,200-1,500 kcal/day adjusted for individual requirements 2
• Any balanced dietary approach creating an energy deficit is acceptable—no specific diet type is superior in PCOS 2

Exercise Requirements:

• For weight maintenance: ≥150 minutes/week moderate-intensity OR 75 minutes/week vigorous activity, PLUS muscle-strengthening on 2 non-consecutive days/week 2
• For weight loss: ≥250 minutes/week moderate-intensity OR 150 minutes/week vigorous activity, PLUS muscle-strengthening on 2 non-consecutive days/week 2

Behavioral Components:

• Incorporate goal-setting, self-monitoring, stimulus control, problem-solving, assertiveness training, slower eating, reinforcement of changes, and relapse prevention 2

Step 2: Treatment Based on Reproductive Goals

For Women NOT Attempting to Conceive:

Combined oral contraceptives (COCs) are first-line hormonal therapy, as they suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne. 2

Second-line for persistent hirsutism/acne:

• Add spironolactone (antiandrogen) to oral contraceptives 2

For Women Attempting to Conceive:

Clomiphene citrate is the first-line pharmacological treatment for ovulation induction, with approximately 80% of patients ovulating and 50% of ovulators conceiving. 2

If clomiphene fails:

• Use low-dose gonadotropin therapy due to lower risk of ovarian hyperstimulation compared to higher doses 2

Step 3: Metabolic Management

Add metformin (500-2000 mg daily) when:

• Insulin resistance or glucose intolerance is documented 2
• Lifestyle modifications alone are insufficient for metabolic control 2
• Patient has obesity or elevated cardiovascular risk factors 2

Metformin improves insulin sensitivity and reduces risk factors for diabetes and cardiovascular disease. 2

Emerging therapies:

• GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions 2

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Long-Term Monitoring

Screen ALL patients with PCOS for metabolic abnormalities regardless of body weight, as insulin resistance affects both lean and overweight women. 1

Annual screening should include:

• Repeat glucose tolerance testing (especially in obese women due to rapid progression risk) 2, 1
• Fasting lipid profile 2
• Blood pressure monitoring 1
• Mental health assessment for depression, anxiety, and eating disorders 2

Additional surveillance:

• Screen for obstructive sleep apnea 2
• Monitor for endometrial hyperplasia risk due to chronic anovulation 2
• Use ethnic-specific BMI and waist circumference categories for ethnic groups at high cardiometabolic risk (Asian, Hispanic, South Asian) 2

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Critical Pitfalls to Avoid

• Never neglect metabolic screening in normal-weight PCOS patients—insulin resistance occurs independently of BMI 1
• Do not exceed recommended clomiphene dosage and duration 2
• Do not use ultrasound for diagnosis in adolescents <8 years post-menarche 1
• Do not use serum anti-Müllerian hormone (AMH) as a single test for PCOS diagnosis or as an alternative to ultrasound 1
• Always exclude other causes of hyperandrogenism (thyroid disease, hyperprolactinemia, congenital adrenal hyperplasia, Cushing's syndrome, androgen-secreting tumors) before confirming PCOS diagnosis 1