What medications are used to treat Polycystic Ovary Syndrome (PCOS)?

PCOS Medication Treatment

Combined oral contraceptives (COCs) are the first-line medication for women with PCOS who are not attempting to conceive, while clomiphene citrate is the first-line treatment for those seeking fertility. 1, 2

Treatment Algorithm Based on Reproductive Goals

For Women NOT Attempting to Conceive

Start with lifestyle modification targeting 5% weight loss through diet and exercise, then add COCs as primary pharmacologic therapy. 1, 2

Primary Medication: Combined Oral Contraceptives

• COCs suppress ovarian androgen secretion, increase sex hormone binding globulin, and reduce endometrial cancer risk 3, 1
• Formulations containing norgestimate (like Sprintec) are preferred due to favorable side effect profiles 1
• Start within first 5 days of menstrual bleeding (no backup contraception needed), or anytime if pregnancy excluded (use backup contraception for 7 days) 1
• COCs increase venous thromboembolism risk 3-4 fold above baseline (from 1 per 10,000 to 3-4 per 10,000 woman-years) 1

Alternative: Progestin-Only Regimens (when COCs contraindicated)

• Medroxyprogesterone acetate 10 mg daily for 12-14 days per month is the only progestin with robust evidence for inducing secretory endometrium and providing endometrial protection 1
• Oral micronized progesterone 200 mg daily for 12-14 days per month offers superior cardiovascular and thrombotic safety profile 1
• Monthly cycling (every 28 days) is essential to maintain endometrial protection 1

Metabolic Management

• Metformin 1-1.5g daily (typically divided twice daily) improves insulin sensitivity, reduces testosterone levels, and tends to decrease weight 2
• Consider metformin particularly in women with abdominal obesity and insulin resistance 2
• Metformin improves or maintains glucose tolerance over time 3
• GLP-1 receptor agonists (semaglutide, liraglutide, exenatide) improve metabolic parameters and promote weight loss 2

Hirsutism Management

• Combine an antiandrogen (spironolactone, flutamide, or finasteride) with COCs for optimal hirsutism control 3, 1
• Topical eflornithine hydrochloride cream is the only FDA-approved medication specifically for hirsutism 3
• Mechanical hair removal (electrolysis, laser) typically requires concomitant medical management 3

For Women Attempting to Conceive

Begin with weight loss (5-10% of body weight) and exercise, then proceed directly to clomiphene citrate as first-line ovulation induction. 2, 4

First-Line Ovulation Induction

• Clomiphene citrate is the first-line treatment with good and consistent evidence: 80% of PCOS patients ovulate, and 50% of those who ovulate conceive 3, 2, 5
• Start at 50 mg daily for 5 days, escalate to 100 mg then 150 mg in subsequent cycles if ovulation does not occur 4
• Begin on or about day 5 of the cycle 5
• Limit to approximately 6 total cycles (including 3 ovulatory cycles) 5
• Letrozole demonstrates superior live birth rates and pregnancy rates compared to clomiphene 4

Second-Line Options (if clomiphene fails)

• Low-dose gonadotropin therapy is preferred over high-dose protocols due to higher monofollicular development rates and lower ovarian hyperstimulation risk 3, 4

Adjunctive Metabolic Treatment

• Metformin improves ovulation frequency and should be used as adjunct to lifestyle modification and ovulation induction agents, not as primary fertility treatment 4
• Metformin appears safe in pregnancy and may reduce miscarriage rates 4
• Weight loss of even 5% improves ovulation and pregnancy rates 3, 4
• Exercise (at least 250 minutes/week of moderate-intensity) benefits PCOS even without weight loss 4

Essential Metabolic Screening

All women with PCOS require screening for type 2 diabetes (fasting glucose and 2-hour glucose tolerance test) and dyslipidemia (fasting lipid profile), regardless of weight or symptoms. 1, 4

Critical Pitfalls to Avoid

• Never use spironolactone in women attempting pregnancy - it is contraindicated in pregnancy 4
• Do not exceed clomiphene dosage/duration recommendations as this worsens endometrial receptivity 4
• Do not use metformin as primary fertility treatment - clomiphene is significantly more effective for ovulation induction 2
• Thiazolidinediones tend to increase weight (unlike metformin which decreases weight), making them less favorable for most PCOS patients 3, 2
• No insulin-sensitizing agents are FDA-approved specifically for PCOS treatment 3