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

PCOS Workup and Treatment

Diagnose PCOS using the Rotterdam criteria—requiring at least two of three findings: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and polycystic ovarian morphology on ultrasound—after excluding other causes of androgen excess. 1

Diagnostic Workup

Clinical Assessment

• Measure total or free testosterone using mass spectrometry (LC-MS/MS) as first-line testing, which demonstrates 92% specificity compared to 78% for direct immunoassays 1
• Check 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1
• Measure TSH to exclude thyroid disease causing menstrual irregularity 1
• Check prolactin levels to exclude hyperprolactinemia 1
• Calculate BMI and waist-to-hip ratio to assess central obesity 1
• Examine for acanthosis nigricans on neck, axillae, under breasts, and vulva—this indicates underlying insulin resistance 1

Imaging

• Perform transvaginal ultrasound (if sexually active and acceptable to patient) using transducers with ≥8 MHz frequency 2, 1
• Diagnostic threshold: ≥25 follicles (2-9 mm diameter) in at least one ovary OR ovarian volume >10 mL 2
• Do not use ultrasound for diagnosis in adolescents with gynecological age <8 years post-menarche due to physiologically normal multifollicular ovaries 1
• Use transabdominal ultrasound for non-sexually active patients, focusing on ovarian volume ≥10 mL 1
• Consider MRI without IV contrast only in obese patients where ultrasound is inadequate 2

Metabolic Screening (All PCOS Patients Regardless of BMI)

• Perform 2-hour oral glucose tolerance test with 75-gram glucose load to detect type 2 diabetes and glucose intolerance—insulin resistance occurs independent of body weight 3, 1
• Obtain fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) as insulin resistance drives atherogenic dyslipidemia with elevated triglycerides, increased small dense LDL, and decreased HDL 3

Treatment Algorithm

Step 1: Lifestyle Modification (Foundation for ALL Patients)

Initiate multicomponent lifestyle intervention before or concurrent with any pharmacologic therapy—this is the foundation of the treatment hierarchy regardless of pregnancy goals. 3

• Target 5% weight loss, which improves metabolic parameters, ovulation rates, and pregnancy outcomes 2, 3
• Prescribe ≥250 minutes per week of moderate-intensity activity or 150 minutes per week of vigorous activity, plus muscle-strengthening exercises on 2 non-consecutive days 4
• Reduce soft drinks, fruit juices, and sugar-sweetened beverages 4
• Incorporate behavioral strategies: goal-setting, self-monitoring, stimulus control, problem-solving, assertiveness training, slower eating, reinforcement of changes, and relapse prevention 4

Step 2A: For Women NOT Seeking Pregnancy

Use combination oral contraceptive pills as first-line treatment to regulate menstrual cycles, provide endometrial protection, and suppress ovarian androgen secretion. 2

• OCPs may increase triglycerides and HDL cholesterol but do not increase cardiovascular events compared to the general population 2, 3
• Add metformin as the preferred insulin-sensitizing agent when pharmacologic intervention is warranted 3
• Metformin decreases circulating androgens through improved insulin sensitivity 2, 3
• Metformin improves glucose tolerance over time and tends to decrease weight (unlike thiazolidinediones which increase weight) 2, 3
• For hirsutism: combine antiandrogen (spironolactone) with oral contraceptives as most effective approach 2

Step 2B: For Women Seeking Pregnancy

Begin with weight control and regular exercise, then use clomiphene citrate as first-line ovulation induction—approximately 80% ovulate and 50% conceive. 2, 5

• Start clomiphene at 50 mg daily for 5 days, beginning on day 5 of the cycle 5
• Time coitus 5-10 days after completing clomiphene course when ovulation most often occurs 5
• Increase to 100 mg daily for 5 days only if ovulation does not occur after first course 5
• Do not exceed 100 mg/day for 5 days—increasing dosage or duration beyond this is not recommended 5
• Discontinue after 3 ovulatory cycles without pregnancy or after 6 total cycles 5
• If clomiphene fails, use low-dose gonadotropin therapy to minimize ovarian hyperstimulation risk 2

Step 3: Advanced Metabolic Management

Consider GLP-1 receptor agonists (semaglutide, liraglutide) if lifestyle modifications plus metformin prove insufficient after 3-6 months, particularly for patients with BMI ≥27 with comorbidities or ≥30 without comorbidities. 4

Critical Pitfalls to Avoid

• Do not overlook acanthosis nigricans—while typically indicating insulin resistance, it may rarely indicate associated insulinoma or gastric adenocarcinoma 3
• Do not use thiazolidinediones as first-line agents—they increase weight and have less favorable risk-benefit profiles compared to metformin 2, 3
• Do not skip metabolic screening in lean women—insulin resistance occurs independent of BMI and affects both lean and overweight women 3
• Do not use ultrasound alone for diagnosis—PCOS requires clinical criteria (hyperandrogenism and/or ovulatory dysfunction) in addition to imaging findings 1
• Do not use ovarian morphology for diagnosis in adolescents <8 years post-menarche 1