What are the diagnosis and treatment guidelines for a patient with Polycystic Ovary Syndrome (PCOS)?

Diagnosis and Treatment Guidelines for PCOS

Diagnostic Criteria and Workup

Diagnose PCOS using the Rotterdam criteria, requiring at least 2 of 3 findings: hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology on ultrasound, after excluding other causes of androgen excess. 1

Laboratory Testing

• Measure total or free testosterone using mass spectrometry as first-line testing (92% specificity vs 78% for direct immunoassays) 1
• Check 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1
• Measure TSH to exclude thyroid disease causing menstrual irregularity 1
• Perform 2-hour oral glucose tolerance test with 75-gram glucose load to detect type 2 diabetes and glucose intolerance, as insulin resistance occurs independent of body weight 1
• Obtain fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides 2, 3
• Calculate BMI and waist-hip ratio using ethnic-specific cutoffs (lower thresholds for Asian, Hispanic, and South Asian populations) 4, 3

Imaging

• Perform transvaginal ultrasound using transducers with ≥8 MHz frequency, with diagnostic threshold of ≥25 follicles in at least one ovary or ovarian volume >10 mL 1

First-Line Treatment: Multicomponent Lifestyle Intervention

All women with PCOS, regardless of body weight, should receive multicomponent lifestyle intervention as first-line management, combining dietary modification, structured physical activity, and behavioral strategies, because insulin resistance affects all PCOS patients independent of BMI. 4, 1

Dietary Management

• Target energy deficit of 500-750 kcal/day (1,200-1,500 kcal/day total) for weight loss in overweight/obese patients 4
• Focus on low glycemic index foods, high-fiber diets, omega-3 fatty acids, and anti-inflammatory dietary patterns 4
• Reduce soft drinks, fruit juices, and sugar-sweetened beverages 1
• Aim for 5-10% weight loss, which yields significant clinical improvements in metabolic parameters, ovulation rates, and pregnancy outcomes 4, 1

Physical Activity Prescription

• Prescribe at least 150 minutes/week of moderate-intensity exercise or 75 minutes/week of vigorous-intensity activity 4, 1
• Include muscle-strengthening activities on 2 non-consecutive days per week 4, 1
• For overweight patients, increase to at least 250 minutes/week of moderate-intensity or 150 minutes/week of vigorous-intensity activity 4
• Perform activity in at least 10-minute bouts, aiming for 10,000 steps daily including 30 minutes of structured activity 4
• Minimize sedentary, screen, and sitting time 4

Behavioral Strategies

• Implement SMART (specific, measurable, achievable, realistic, timely) goal setting with self-monitoring using fitness tracking devices 4
• Include goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 4
• Address psychological factors including anxiety, depression, body image concerns, and disordered eating 4, 3
• Start with realistic 10-minute activity bouts, progressively increasing by 5% weekly 4

Medical Management for Women NOT Attempting to Conceive

Combined oral contraceptive pills are first-line hormonal therapy for women with PCOS not attempting to conceive, as they suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne. 2, 4

Hormonal Contraception

• Use drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen, taken daily 4
• OCPs reduce risk of endometrial cancer, though the extent of this effect in PCOS is unknown 2
• Be aware that OCP use is associated with significant increases in circulating triglyceride and HDL cholesterol levels 2
• Document individual risk factors before prescribing (age, smoking, obesity, glucose intolerance, hypertension, dyslipidemia, thrombophilia, personal/family history of venous thromboembolism) 5

Alternative Progestin Therapy

• Medroxyprogesterone acetate (depot or intermittent oral) suppresses circulating androgen and pituitary gonadotropin levels 2
• The optimal progestin, duration, and frequency to prevent endometrial cancer in PCOS is not known 2

Insulin-Sensitizing Agents

• Prescribe metformin 500-2000 mg daily for patients with insulin resistance or glucose intolerance, starting at 500 mg daily and titrating to 1000-2000 mg daily in divided doses 4, 1
• Metformin improves glucose tolerance over time and may have positive impact on risk factors for diabetes and cardiovascular disease 2
• Consider GLP-1 receptor agonists (liraglutide, semaglutide, exenatide) in combination with lifestyle interventions for weight loss and metabolic control, particularly if lifestyle plus metformin prove insufficient after 3-6 months 4, 1

Antiandrogen Therapy for Hirsutism

• Use spironolactone (50-200 mg daily) or finasteride for persistent bothersome hirsutism, combined with mechanical hair removal methods 3
• Topical eflornithine hydrochloride cream is FDA-approved for hirsutism and can be used adjunctively 3
• Combined medical interventions (antiandrogen plus ovarian suppression agent) may be most effective for hirsutism 2

Medical Management for Women ATTEMPTING to Conceive

Clomiphene citrate is first-line pharmacological treatment for ovulation induction in women with PCOS attempting to conceive, with approximately 80% of patients ovulating and 50% conceiving. 2, 1, 6

Ovulation Induction Protocol

• Start with weight control and regular exercise program before medication 2
• Use clomiphene citrate as first-line therapy due to its effectiveness, safety, and ease of administration 2, 1
• Start patients with polycystic ovary syndrome on the lowest recommended dose and shortest treatment duration for the first course, as they may have exaggerated response to usual doses 6
• If clomiphene treatment fails, use low-dose (rather than high-dose) gonadotropin therapy, which induces high rate of monofollicular development with lower risk of ovarian hyperstimulation 2
• Consider metformin 1 g twice daily for 12 weeks or until pregnancy in the pregestational stage 4

Critical Warnings for Clomiphene Use

• Monitor for visual symptoms (blurring, scotomata, phosphenes)—discontinue immediately and perform complete ophthalmological evaluation if any visual symptoms occur 6
• Watch for early warning signs of ovarian hyperstimulation syndrome (OHSS): abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain 6
• If ovarian enlargement occurs, do not give additional clomiphene until ovaries return to pretreatment size, and reduce dosage or duration of next course 6
• Perform abdominal and pelvic examination very cautiously due to fragility of enlarged ovaries in severe cases 6

Long-Term Monitoring and Follow-Up

Metabolic Surveillance

• Screen for type 2 diabetes using fasting glucose followed by 2-hour glucose level after 75-gram oral glucose load, repeating annually or every 1-2 years based on BMI and family history 3
• Monitor fasting lipid profile regularly 3
• Calculate BMI and waist-hip ratio at each visit 3
• Obese women require regular glucose tolerance testing due to potential for rapid progression from normal to impaired glucose tolerance and diabetes 7

Monitoring Schedule

• Fortnightly review for first 3 months with structured dietary and physical activity plans 4
• Regular review for first 12 months to ensure adherence and adjust interventions 4
• Regular monitoring of weight and waist circumference during weight loss and maintenance 4

Special Population Considerations

• Begin prevention of weight gain and monitoring from adolescence, as weight gain escalates from this period 4
• Use ethnic-specific BMI and waist circumference categories for Asian, Hispanic, and South Asian populations, who require lower thresholds and greater consideration for lifestyle intervention 4, 3
• Ensure health professional interactions are respectful and patient-centered, avoiding weight-related stigma which negatively impacts treatment engagement 4

Management in Menopause

Metabolic Risk Management

• Continue multicomponent lifestyle intervention targeting at least 150 minutes/week of moderate-intensity physical activity 3
• Prescribe metformin (500-2000 mg daily) for documented insulin resistance, glucose intolerance, or established type 2 diabetes to reduce cardiovascular and metabolic risk 3
• Consider newer anti-obesity agents (GLP-1 receptor agonists) for weight management when lifestyle interventions alone are insufficient 3

Hormone Replacement Therapy

• Standard menopausal HRT guidelines apply—transdermal 17-β estradiol is preferred over oral formulations to minimize thrombotic risk 3
• Consider HRT for vasomotor symptoms and bone protection, continuing until at least average age of natural menopause 3

Continued Hyperandrogenic Symptom Management

• Continue antiandrogen therapy with spironolactone (50-200 mg daily) or finasteride for persistent hirsutism 3
• Screen for depression, anxiety, and body image concerns, as PCOS has significant negative impact on psychological wellbeing that persists into menopause 3