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

Medications for Polycystic Ovary Syndrome (PCOS)

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

Treatment Algorithm Based on Reproductive Goals

For Women NOT Seeking Pregnancy

COCs should be prescribed as primary therapy to suppress ovarian androgen secretion, increase sex hormone binding globulin, regulate menstrual cycles, and reduce endometrial cancer risk. 1, 2

Specific COC Recommendations:

• COCs containing norgestimate (e.g., Sprintec) are preferred due to their favorable side effect profile 1
• Alternative formulations include ethinyl estradiol 30 mcg with drospirenone 3 mg, which effectively treats hyperandrogenism 3
• Start within first 5 days of menstrual bleeding (no backup contraception needed), or anytime if pregnancy excluded (use backup contraception for 7 days) 1
• Standard regimen: 21-24 hormone pills followed by 4-7 placebo pills 1

Important caveat: COCs increase venous thromboembolism risk three to fourfold above baseline (from 1 per 10,000 to 3-4 per 10,000 woman-years). 1, 4 Screen for risk factors including age, smoking, obesity, glucose intolerance, hypertension, dyslipidemia, thrombophilia, and family history of VTE before prescribing. 5

When COCs Are Contraindicated or Not Tolerated:

Use cyclic progestins for endometrial protection:

• Medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days per month is the only progestin with robust evidence for inducing secretory endometrium 1
• Alternative: Oral micronized progesterone 200 mg daily for 12-14 days per month (superior safety profile with lower cardiovascular and thrombotic risk) 1
• Alternative: Dydrogesterone 10 mg daily for 12-14 days per month 1
• Cycle monthly (every 28 days) to maintain endometrial protection 1

For Women Seeking Pregnancy

Clomiphene citrate is first-line ovulation induction therapy, with 80% of PCOS patients ovulating and 50% of those conceiving. 1, 2

Critical warning: Visual symptoms (blurring, scotomata, diminished acuity) can occur with clomiphene and require immediate discontinuation and ophthalmologic evaluation. 6 Ovarian hyperstimulation syndrome (OHSS) may progress rapidly to a serious medical disorder with gross ovarian enlargement, ascites, dyspnea, oliguria, and potentially death from hypovolemic shock or thromboembolism. 6

For clomiphene non-responders: Low-dose gonadotropin therapy is preferred over high-dose therapy. 1, 2

Management of Hirsutism and Hyperandrogenism

Combine antiandrogens with COCs for optimal hirsutism control (more effective than either alone). 1, 2

Antiandrogen Options:

• Spironolactone (most commonly used) 2, 7
• Flutamide 1, 2
• Finasteride 1, 2

Specific combination regimen: Ethinyl estradiol/drospirenone plus spironolactone 100 mg/day significantly improves hirsutism scores and testosterone levels. 7 However, this combination increases hsCRP and homocysteine levels (inflammatory markers), though without adverse effects on glucose tolerance or lipid profile. 7

Topical option: Eflornithine hydrochloride cream is FDA-approved for hirsutism, though additional benefits in PCOS are unknown. 2

Metabolic Management

All women with PCOS require metabolic screening:

• Fasting glucose and 2-hour glucose tolerance test for type 2 diabetes 1, 2
• Fasting lipid profile for dyslipidemia 1, 2

Metformin Use:

Metformin improves insulin sensitivity, reduces insulin and androgen levels, and promotes weight loss. 1, 2 In South Asian populations with high insulin resistance prevalence, metformin regularizes menstrual cycles in 72% of patients and effectively treats hyperandrogenism. 8

• Metformin maintains or improves glucose tolerance over time 1
• Tends to decrease weight (unlike thiazolidinediones which increase weight) 1

Emerging therapies: GLP-1 receptor agonists (liraglutide, semaglutide) show promise for weight management, with semaglutide appearing most potent. 2

Lifestyle Modifications

Weight loss of just 5% of initial body weight improves metabolic and reproductive abnormalities. 1, 2 Regular exercise benefits PCOS even without weight loss. 1