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

Medication Treatment for Polycystic Ovary Syndrome (PCOS)

Combined oral contraceptives (COCs) are the first-line medication treatment for long-term management of PCOS in women who are not attempting to conceive, while clomiphene citrate is the first-line treatment for women with PCOS who wish to conceive. 1, 2

Treatment Based on Reproductive Goals

For Women Not Seeking Pregnancy:

• Combined oral contraceptives (COCs) are first-line therapy for regulating menstrual cycles, providing endometrial protection, and suppressing ovarian androgen secretion 1, 3
• COCs increase circulating sex hormone binding globulin and reduce the risk of endometrial cancer in women with PCOS 1
• Medroxyprogesterone acetate can be used to suppress circulating androgen levels and pituitary gonadotropin levels 1

For Women Seeking Pregnancy:

• Treatment begins with weight control and regular exercise program before medication 4
• Clomiphene citrate is the first-line ovulation induction treatment with approximately 80% of PCOS patients ovulating and half of these conceiving 4, 2
• Low-dose gonadotropin therapy is preferred over high-dose therapy for women who don't respond to clomiphene 4
• Metformin may be used to improve insulin sensitivity and ovulation rates, particularly when combined with other fertility treatments 5, 6

Management of Hirsutism and Hyperandrogenism

• A combined approach with antiandrogens and COCs is more effective for hirsutism than either treatment alone 1, 3
• Commonly used antiandrogens include spironolactone, flutamide, and finasteride 1
• Topical eflornithine hydrochloride cream is FDA-labeled for hirsutism treatment, though additional benefits in PCOS are unknown 4
• Mechanical hair removal (plucking, shaving, waxing), electrolysis, and laser treatments can be used alongside medical management 4

Management of Metabolic Aspects

• All women with PCOS should be screened for type 2 diabetes with fasting glucose and 2-hour glucose tolerance test 1, 3
• Regular screening for dyslipidemia with fasting lipid profile is recommended 1, 3
• Metformin improves insulin sensitivity, reducing insulin levels and subsequently decreasing ovarian androgen production 7, 5
• Weight loss (even 5% of initial weight) improves metabolic and reproductive abnormalities in PCOS 1, 7
• Regular exercise is beneficial for women with PCOS, even without weight loss 1

Emerging Treatments

• GLP-1 receptor agonists (liraglutide, semaglutide) show promise for weight management in PCOS, with liraglutide demonstrating superiority to placebo for anthropometric outcomes 4
• Semaglutide appears to be the most potent GLP-1 receptor agonist but has limited studies in PCOS 4
• Exenatide twice daily did not show significant benefits over metformin and was associated with more adverse events 4

Important Clinical Considerations

• Clomiphene citrate should not be used in patients with ovarian cysts (except those with PCOS), abnormal vaginal bleeding, or liver dysfunction 2
• Long-term cyclic therapy with clomiphene is not recommended beyond a total of about six cycles 2
• Metformin is not FDA-approved specifically for PCOS treatment but is widely used off-label 5
• Metformin may reduce early pregnancy loss and preterm birth when continued during pregnancy, though evidence is mixed 5, 6
• Combination of metformin with clomiphene citrate is more effective than either alone for clomiphene-resistant PCOS 6

Treatment Algorithm Based on Primary Symptom

1. Irregular menstrual cycles: COCs for women not seeking pregnancy; clomiphene citrate for women seeking pregnancy 1, 2
2. Hirsutism/acne: COCs plus antiandrogens (spironolactone most common) 1
3. Metabolic concerns: Metformin plus lifestyle modifications 7, 5
4. Infertility: Clomiphene citrate first-line; add metformin for clomiphene resistance; low-dose gonadotropins if still no response 4, 2, 6