What are the treatment options for Polycystic Ovary Syndrome (PCOS)?

PCOS Treatment

Lifestyle modification with diet and exercise is the first-line treatment for all women with PCOS regardless of body weight, targeting a 5-10% weight loss through a 500-750 kcal/day deficit, combined with at least 150 minutes weekly of moderate-intensity exercise. 1, 2

Treatment Algorithm by Clinical Goal

For Women NOT Attempting Pregnancy

Step 1: Lifestyle Intervention (All Patients)

• Implement a balanced diet with 30% energy deficit or 500-750 kcal/day reduction (targeting 1,200-1,500 kcal/day based on individual needs) 3
• Prescribe at least 150 minutes/week of moderate-intensity physical activity OR 75 minutes/week of vigorous-intensity activity 3
• Include resistance training on 2 non-consecutive days weekly 3
• Both aerobic and resistance exercise improve insulin sensitivity independent of weight loss 3, 4
• Even 5% weight loss significantly improves metabolic and reproductive outcomes 2, 5

Step 2: Hormonal Management

• Combined oral contraceptives are the preferred treatment for menstrual regulation and androgen suppression in women not seeking pregnancy 1
• OCPs suppress ovarian androgen secretion and increase sex hormone-binding globulin 1
• OCPs reduce endometrial cancer risk, though the magnitude of benefit in PCOS is unknown 1
• Alternative: Medroxyprogesterone acetate (depot or intermittent oral) suppresses androgens and gonadotropins, though optimal dosing for endometrial protection is unclear 1

Step 3: Metabolic Management

• Metformin is recommended to improve insulin sensitivity and has favorable effects on weight (tends to decrease weight) 1
• Metformin improves or maintains glucose tolerance over time 1, 5
• Thiazolidinediones (pioglitazone, rosiglitazone) are alternatives but tend to increase weight 1
• Neither metformin nor thiazolidinediones are FDA-approved for PCOS treatment 1

Step 4: Screening and Monitoring

• Screen all PCOS patients for dyslipidemia with fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) 1
• Calculate BMI and waist-hip ratio using ethnic-specific cutoffs 1, 3
• Monitor for cardiovascular risk factors, as OCPs may increase triglycerides and HDL but do not increase cardiovascular events compared to general population 1

For Women Attempting Pregnancy

Step 1: Lifestyle Optimization (Mandatory First Step)

• Weight loss and exercise must be implemented before pharmacologic therapy 1, 5
• Target 5% weight loss, which significantly improves ovulation and pregnancy rates 5
• This is non-negotiable foundational therapy 5

Step 2: First-Line Ovulation Induction

• Clomiphene citrate is the FDA-approved and guideline-recommended first-line agent 1, 6
• Achieves 80% ovulation rate, with 50% of ovulators conceiving 1, 5
• Start on day 5 of cycle, limit to 6 total cycles (including 3 ovulatory cycles) 6
• Recent evidence suggests letrozole may be more effective than clomiphene, though clomiphene remains the guideline-recommended agent 7

Step 3: Adjunctive Insulin Sensitizers

• Metformin improves ovulation frequency and appears safe in pregnancy, though early pregnancy effects are not fully established 1, 2, 5
• Metformin reduces insulin levels, subsequently decreasing ovarian androgen production 5
• Can be used alongside clomiphene 1

Step 4: Second-Line Ovulation Induction

• If clomiphene fails, use low-dose gonadotropin therapy (not high-dose) 1
• Low-dose regimens induce monofollicular development with lower ovarian hyperstimulation risk 1

Step 5: Preconception and Pregnancy Management

• Provide preconception counseling about increased pregnancy risks 5
• Screen metabolic parameters before conception: fasting glucose, 2-hour glucose tolerance test, lipid profile 5
• Once pregnant, monitor blood pressure, kidney function, and proteinuria closely 5
• Prescribe low-dose aspirin from week 12 to week 36 to reduce preeclampsia risk 5

Critical Considerations Across All Body Types

Insulin Resistance Affects ALL PCOS Patients

• Insulin resistance is present regardless of BMI in both lean and overweight women with PCOS 3
• Hyperinsulinemia contributes to hyperandrogenism through effects on pituitary, liver, and ovaries in all women regardless of weight 3
• Do not skip lifestyle intervention in normal-weight PCOS patients—insulin resistance requires management independent of BMI 3

Behavioral and Psychological Support

• Implement SMART goal setting (specific, measurable, achievable, realistic, timely) and self-monitoring 3
• Address anxiety, depression, body image concerns, and disordered eating to optimize adherence 3, 8
• Consider comprehensive cognitive behavioral interventions to increase engagement 3
• Ensure respectful, patient-centered interactions avoiding weight-related stigma 3

Common Pitfalls to Avoid

Ovarian Hyperstimulation Syndrome (OHSS)

• PCOS patients are unusually sensitive to gonadotropins and may have exaggerated response to clomiphene 6
• Start with lowest recommended clomiphene dose and shortest duration for first course 6
• Early warning signs: abdominal pain/distention, nausea, vomiting, diarrhea, weight gain 6
• If ovarian enlargement occurs, do not give additional clomiphene until ovaries return to pretreatment size 6

Visual Disturbances with Clomiphene

• Discontinue clomiphene immediately if visual symptoms develop (blurring, scotomata, phosphenes) 6
• Perform complete ophthalmologic evaluation promptly 6

Endometrial Cancer Risk

• PCOS increases endometrial cancer risk due to unopposed estrogen from chronic anovulation 1
• Perform endometrial biopsy before clomiphene therapy in older patients 6
• OCPs or cyclic progestins provide endometrial protection 1

Unproven Therapies

• Do not recommend herbal supplements (including evening primrose oil) as primary therapy—no evidence supports their use 3
• Patients should not delay evidence-based treatment while pursuing unproven complementary therapies 3