What are the common treatments for a female patient of reproductive age with Polycystic Ovary Syndrome (PCOS) and no significant medical history?

Management of Polycystic Ovary Syndrome (PCOS)

Lifestyle modification combining diet, exercise, and behavioral strategies is the foundational first-line treatment for all women with PCOS, regardless of body weight, because insulin resistance affects both lean and overweight patients and drives the pathophysiology of PCOS. 1

First-Line Treatment: Lifestyle Intervention

Dietary Management

• Implement an energy deficit of 500-750 kcal/day (targeting 1,200-1,500 kcal/day total) for women with overweight or obesity 1
• No specific diet type is superior—any balanced approach creating an energy deficit is acceptable, prioritizing patient preferences and cultural needs 1, 2
• Focus on low glycemic index foods, high-fiber diets, omega-3 fatty acids, Mediterranean diet patterns, or anti-inflammatory diets to improve insulin sensitivity 1
• Avoid restrictive or nutritionally unbalanced diets 1
• Critical pitfall: Do not dismiss dietary intervention in lean PCOS patients—insulin resistance requires management regardless of BMI 1

Physical Activity Prescription

• Prescribe at least 150 minutes/week of moderate-intensity exercise OR 75 minutes/week of vigorous-intensity activity 1
• Include muscle-strengthening activities on 2 non-consecutive days/week 1
• Perform activity in at least 10-minute bouts, aiming for 30 minutes daily on most days 1
• For weight loss: increase to at least 250 minutes/week of moderate-intensity OR 150 minutes/week of vigorous-intensity activity 1
• Both aerobic and resistance exercises show benefits in PCOS 1, 3
• Minimize sedentary, screen, and sitting time throughout the day 1

Behavioral Strategies

• Implement SMART goal setting (specific, measurable, achievable, realistic, timely) with self-monitoring using fitness tracking devices 1
• Include goal-setting, stimulus control, problem-solving, assertiveness training, slower eating, reinforcing changes, and relapse prevention 1
• Consider comprehensive behavioral or cognitive behavioral interventions to increase adherence 1
• Address psychological factors including anxiety, depression, body image concerns, and eating disorders—these dramatically reduce treatment adherence 1
• Target achievable weight loss of 5-10% in those with excess weight, which yields significant clinical improvements 1, 3

Medical Management for Women NOT Attempting to Conceive

Hormonal Therapy

• Combined oral contraceptive pills (COCPs) are first-line hormonal therapy for menstrual cycle regulation, endometrial protection, and management of hyperandrogenism 4, 1
• COCPs suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne 4, 1
• Typical regimen: drospirenone 3 mg/ethinyl estradiol 20 μg in a 24-active/4-inert pill regimen 4
• Alternative: medroxyprogesterone acetate (depot or intermittent oral) suppresses androgens and gonadotropins, though optimal dosing for endometrial protection is not established 4

Insulin-Sensitizing Agents

• Metformin 1.5-2 g daily (divided into twice-daily dosing) is first-line for metabolic management 2
• Start at 500 mg daily and titrate up to 1,000-2,000 mg daily in divided doses to minimize gastrointestinal side effects 1, 2
• Metformin improves glucose tolerance, reduces diabetes risk, decreases LDL cholesterol and triglycerides, and may reduce cardiovascular disease risk 4, 2
• Metformin tends to decrease weight, unlike thiazolidinediones which cause weight gain 4, 2
• Critical pitfall: Do not continue metformin into pregnancy without careful consideration of emerging evidence showing potential adverse offspring metabolic outcomes 2

Anti-Obesity Pharmacological Agents

• GLP-1 receptor agonists (liraglutide 1.8-3 mg daily, semaglutide 1-2 mg weekly, or exenatide 5-10 μg twice daily or 2 mg weekly) are second-line for women with obesity or inadequate response to metformin 4, 1, 2
• GLP-1 agonists promote weight loss, improve metabolic parameters, and reduce androgens 4, 2
• Orlistat 120 mg three times daily plus lifestyle intervention can be considered as adjunctive therapy for weight loss 4, 1
• Always combine pharmacological agents with lifestyle interventions 4

Antiandrogen Therapy

• Combined medical interventions (antiandrogen plus ovarian suppression agent) are most effective for severe hirsutism 4, 1
• Add antiandrogens to estrogen-progestin therapy for women with severe hirsutism 5

Medical Management for Women ATTEMPTING to Conceive

Ovulation Induction

• Clomiphene citrate is first-line pharmacological treatment for ovulation induction 4, 1, 6, 7
• Approximately 80% of women with PCOS ovulate with clomiphene, and 50% of those conceive 4, 1, 6
• Start clomiphene on or about day 5 of the cycle with properly timed coitus 6
• Long-term cyclic therapy should not exceed 6 total cycles (including 3 ovulatory cycles) 6
• Critical pitfall: Metformin is NOT first-line for fertility—clomiphene is significantly more effective 2

Second-Line Fertility Treatment

• If clomiphene fails, use low-dose gonadotropin therapy (induces high rate of monofollicular development with lower risk of ovarian hyperstimulation) 4, 1
• Metformin 1 g twice daily for 12 weeks or until pregnancy can be used in the pregestational stage to improve fertility outcomes 4, 1
• Letrozole is an alternative first-line option for ovulation induction 7

Monitoring During Fertility Treatment

• Perform pelvic examination prior to first and each subsequent course of clomiphene 6
• Monitor for ovarian hyperstimulation syndrome (OHSS)—early warning signs include abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain 6
• Use lowest effective dose to minimize risk of abnormal ovarian enlargement 6
• Women with PCOS are unusually sensitive to gonadotropins and may have exaggerated response to usual clomiphene doses—start with lowest recommended dose and shortest duration 6

Metabolic and Cardiovascular Risk Management

Screening and Monitoring

• Screen for diabetes risk with fasting glucose, 2-hour oral glucose tolerance test, and HbA1c 7, 8
• Assess cardiovascular risk factors: blood pressure, weight, smoking status, lipid profile 4, 1
• Screen for hepatic steatosis (nonalcoholic fatty liver disease) 9, 8
• Screen for sleep apnea, which occurs more commonly in women with PCOS 9
• Monitor weight and waist circumference regularly, using ethnic-specific cutoffs for Asian, Hispanic, and South Asian populations 1

Long-Term Health Considerations

• Women with PCOS are at increased risk for type 2 diabetes (4 times higher than general population), metabolic syndrome (2 times higher), cardiovascular disease, endometrial cancer, and mood disorders 7, 8
• Interventions improving insulin sensitivity (weight loss, metformin, thiazolidinediones) may positively impact diabetes and cardiovascular disease risk 4

Psychological and Quality of Life Management

Mental Health Screening and Support

• Screen for depression, anxiety, eating disorders (binge eating disorder, night eating syndrome), and body image concerns 1, 9, 8
• Refer patients with moderately severe depression to psychiatry or behavioral health for evaluation and potential pharmacotherapy 1
• Psychological factors require active management to optimize treatment engagement and adherence 1
• Ensure health professional interactions are respectful, patient-centered, and avoid weight-related stigma 1

Special Population Considerations

Adolescents

• Delay evaluation for PCOS until 2 years after menarche 7
• Require all three Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, polycystic ovaries) before diagnosis in adolescents 7
• Prevention of weight gain and monitoring should begin from adolescence 1
• Adolescents should aim for at least 60 minutes of moderate to vigorous intensity physical activity daily, including muscle and bone strengthening activities at least 3 times weekly 1

Ethnic Populations

• Use ethnic-specific BMI and waist circumference thresholds for Asian, Hispanic, and South Asian populations (lower thresholds required) 1
• Ethnic groups at high cardiometabolic risk require greater consideration for lifestyle intervention 1

Treatment Algorithm Summary

1. All patients: Lifestyle modification (diet + exercise + behavioral strategies) targeting 5-10% weight loss if overweight 1, 3

2. Not attempting pregnancy:

   • COCPs for menstrual regulation and hyperandrogenism 4, 1
   • Add metformin 1.5-2 g daily for metabolic management 2
   • Consider GLP-1 agonist if obesity or inadequate response to metformin 2
   • Add antiandrogen for severe hirsutism 4, 5

3. Attempting pregnancy:

   • Weight loss and lifestyle modification first 4, 1
   • Clomiphene citrate as first-line ovulation induction 4, 1, 6
   • Low-dose gonadotropins if clomiphene fails 4, 1
   • Consider metformin as adjunct in pregestational stage 4, 1

4. All patients: Screen and manage metabolic complications, cardiovascular risk factors, and psychological comorbidities 1, 9, 7, 8