What are the primary medication options for a female patient with Polycystic Ovary Syndrome (PCOS)?

Medications for PCOS

Combined oral contraceptive pills (OCPs) are the optimal first-line medication for most women with PCOS, addressing menstrual irregularity, hyperandrogenism (hirsutism/acne), and endometrial protection simultaneously. 1

Treatment Algorithm Based on Primary Goals

For Women NOT Seeking Pregnancy

Menstrual Regulation and Endometrial Protection:

• Combined OCPs serve as first-line therapy, suppressing ovarian androgen secretion, increasing sex hormone-binding globulin, regulating menstrual cycles, and preventing endometrial hyperplasia 1
• Progestin-only therapy (medroxyprogesterone acetate) is an alternative if OCPs are contraindicated, suppressing circulating androgens and pituitary gonadotropins 1

Hyperandrogenism (Hirsutism/Acne):

• Combined OCPs plus spironolactone (100 mg/day) provides superior reduction in hirsutism compared to metformin alone, with mean differences of 4.6 points in hirsutism score and significant reductions in total testosterone, free testosterone, and androstenedione 2
• OCPs alone reduce hirsutism and acne through androgen level reduction 1
• Critical pitfall: Never use spironolactone as monotherapy in patients who may become pregnant due to teratogenic risk 1

Metabolic Management:

• All patients require metabolic screening regardless of weight, including fasting glucose followed by 2-hour glucose tolerance test and fasting lipid profile 1
• Metformin (500-2000 mg daily) should be added when insulin resistance or glucose intolerance is documented, lifestyle modifications alone are insufficient, or patient has obesity or elevated cardiovascular risk factors 1, 3
• Metformin has the strongest evidence base among insulin sensitizers for metabolic outcomes 4, 5

For Women Seeking Pregnancy

Ovulation Induction:

• Clomiphene citrate remains first-line for ovulation induction per ACOG guidelines, with 80% ovulation rate and 50% conception rate among ovulators 4, 3
• Letrozole is also a first-line option for infertility 3
• If clomiphene fails, gonadotropin therapy (preferably low-dose step-up protocol) or laparoscopic ovarian diathermy are alternatives 6

Adjunctive Insulin Sensitizers:

• Metformin can be added to clomiphene, alone or in combination, as first-line agents for ovulation induction 5
• Metformin appears safe during pregnancy and may reduce miscarriage risk in PCOS 1
• Myoinositol 2000 mg twice daily (4000 mg total) plus folic acid 200 mcg twice daily for 2-3 months minimum can be considered as an insulin-sensitizing agent, though evidence is weaker than for metformin 4
• Do not use myoinositol as monotherapy in place of clomiphene when rapid pregnancy is desired 4
• Critical pitfall: Do not use thiazolidinediones in pregnancy; their effects on early pregnancy are poorly documented compared to metformin 1

Essential Foundation: Lifestyle Modification

Weight Loss and Exercise:

• Target 5-10% weight loss through 500-750 kcal/day energy deficit, which improves both metabolic and reproductive abnormalities 1, 4
• Implement at least 150 minutes/week of moderate-intensity exercise, which benefits PCOS symptoms even without weight loss 1
• Weight loss of as little as 5% can improve menstrual disturbances, infertility, and insulin resistance 7, 3
• Critical pitfall: Do not delay lifestyle intervention—it must be the foundation, not an afterthought 1

Comparative Effectiveness Evidence

The most recent high-quality randomized trial comparing COC plus spironolactone versus metformin demonstrated that COC plus spironolactone was significantly more effective for hirsutism, androgen excess, and menstrual dysfunction, with similar cardiometabolic safety profiles and no differences in frequencies of abnormal glucose tolerance, dyslipidemia, or hypertension 2. This supports the guideline recommendation for OCPs as first-line therapy for non-pregnant women.

Important Caveats

• Do not assume normal weight excludes metabolic dysfunction in PCOS; all patients require metabolic surveillance 1
• Hormonal contraceptives are contraindicated in pregnancy, so clear contraception counseling is essential when prescribing to women of reproductive age 5
• Treatment must be individualized based on whether pregnancy is desired, as this fundamentally changes the medication algorithm 3