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

PCOS Workup and Treatment

Diagnostic Workup

Before diagnosing PCOS, you must exclude other causes of androgen excess including Cushing's syndrome, androgen-secreting tumors, nonclassic congenital adrenal hyperplasia, thyroid disease, hyperprolactinemia, and acromegaly. 1

Essential Laboratory Tests

The initial hormone panel must include: 1, 2

• TSH - to rule out thyroid disease 2
• Prolactin - to exclude hyperprolactinemia 2
• Total testosterone OR free/bioavailable testosterone - free testosterone is more sensitive than total testosterone for establishing androgen excess 2, 3
• DHEA-S - helps exclude adrenal androgen-secreting tumors 2

Mandatory Metabolic Screening

All PCOS patients require metabolic assessment due to increased cardiometabolic risk: 2

• Fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load - PCOS patients have significantly increased diabetes risk 2
• Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) - PCOS patients frequently have elevated LDL, elevated triglycerides, and decreased HDL 2
• BMI and waist-hip ratio calculation at initial evaluation 2

Additional Testing for Specific Red Flags

• Urgent total testosterone and DHEA-S if marked virilization or rapid symptom onset (suggests androgen-secreting tumor) 2
• Cushing's screening if buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathies are present 2

Diagnostic Criteria

Diagnosis requires at least 2 of 3 features: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and/or polycystic ovarian morphology, after excluding mimicking conditions. 3, 4 Note that ultrasound is not recommended as first-line investigation in women <17 years of age due to high prevalence of multicystic ovaries in normal adolescents. 3

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Treatment Algorithm

First-Line: Lifestyle Intervention (ALL Patients)

Multicomponent lifestyle intervention including diet, exercise, and behavioral strategies is the first-line treatment for all PCOS patients, regardless of body weight. 1

• Dietary approach: Energy deficit of 500-750 kcal/day, tailored to patient's food preferences and cultural needs, avoiding restrictive or nutritionally unbalanced diets 1
• Physical activity targets: 150 minutes/week of moderate-intensity activity OR 75 minutes/week of vigorous-intensity activity, plus muscle-strengthening activities on 2 non-consecutive days/week 1
• Weight loss goal: 5-10% weight reduction improves reproductive and metabolic consequences 5

Medical Management Based on Primary Concern

For Menstrual Regulation and Hyperandrogenism (Not Attempting Conception)

Combined oral contraceptive pills (COCPs) are the most common long-term management option and first-line pharmacotherapy for women with PCOS who are not attempting to conceive. 1, 2 COCPs effectively lower androgens by suppressing ovarian androgen production and increasing sex hormone-binding globulin. 3

• Anti-androgens can be added for persistent hirsutism/acne through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) 3

For Metabolic Management

Insulin-sensitizing agents, particularly metformin, may be used to improve insulin sensitivity, decrease circulating androgens, and improve glucose tolerance and metabolic outcomes. 1, 2

• Metformin is recommended as an adjunct to lifestyle management for treatment of weight, hormonal and metabolic outcomes, with focus on prevention of weight gain 6
• In lean adolescents, 850 mg daily may be effective; in overweight/obese patients, dose escalation to 1.5-2.5 g daily is likely required 3

For Fertility Concerns

Insulin-sensitizing agents (metformin) improve ovulation frequency based on good and consistent scientific evidence. 2 Clomiphene citrate and aromatase inhibitors are additional options for ovulation induction. 7

For Weight Loss (Adjunct to Lifestyle)

Published data on anti-obesity agents in PCOS are very limited, but GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) and orlistat represent potential future therapies given their effects on weight loss and insulin resistance. 6 However, these are not currently approved specifically for PCOS and should be considered investigational.

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Ongoing Monitoring

• Regular assessment of weight, waist circumference, blood pressure, HbA1c, and lipid status during weight loss and maintenance 1
• Screen for psychological factors including anxiety, depression, body image concerns, and disordered eating 1
• Address dyslipidemia with weight loss and lifestyle modification before drug therapy 2

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Special Considerations

High-Risk Ethnic Groups

Asian, Hispanic, and South Asian populations require lower BMI and waist circumference thresholds for intervention and greater consideration for lifestyle intervention due to high cardiometabolic risk. 1

Adolescents

Diagnosis in adolescents is particularly challenging. 3 In adolescent girls, diagnostic features are menstrual irregularity (persistent oligomenorrhea 2-3 years beyond menarche), clinical hyperandrogenism, and/or hyperandrogenemia—pelvic ultrasound findings are not needed. 8 Adolescents with clinical signs of androgen excess and oligomenorrhea/amenorrhea can be regarded as "at risk for PCOS" even before definitive diagnosis. 8

Common Pitfall

Cycle length >35 days suggests chronic anovulation, but cycle length of 32-35 days or slightly irregular cycles (32-36 days) also needs assessment for ovulatory dysfunction, as ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer. 3