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

Treatment of Polycystic Ovary Syndrome (PCOS)

Weight loss of just 5% of initial body weight through lifestyle modification is the mandatory first-line treatment for all women with PCOS, regardless of reproductive goals, as it improves metabolic, reproductive, and hormonal outcomes. 1, 2

Foundational Lifestyle Intervention (Required for All Patients)

All patients with PCOS must begin with structured lifestyle modification before or concurrent with any pharmacological therapy. 1, 2

• Target an energy deficit of 500-750 kcal/day, with total intake of 1,200-1,500 kcal/day adjusted for individual energy requirements. 2
• Any balanced dietary approach creating an energy deficit is acceptable—no specific diet type (low-carb, Mediterranean, etc.) has proven superior in PCOS. 1, 2
• Prescribe at least 150 minutes/week of moderate-intensity exercise or 75 minutes/week of vigorous activity, plus muscle-strengthening activities on 2 non-consecutive days/week for weight maintenance. 2
• For active weight loss, increase to at least 250 minutes/week of moderate-intensity activity or 150 minutes/week of vigorous activity. 2
• Exercise provides metabolic benefits even without weight loss. 1, 2
• Incorporate behavioral strategies including goal-setting, self-monitoring, stimulus control, problem-solving, and relapse prevention. 2

Treatment Algorithm Based on Reproductive Goals

For Women NOT Attempting to Conceive

Combined oral contraceptive pills (OCPs) are the first-line pharmacological treatment. 1, 2, 3

• OCPs suppress ovarian androgen secretion, increase sex hormone-binding globulin, regulate menstrual cycles, prevent endometrial hyperplasia, and reduce hirsutism and acne. 1, 2, 3
• Any combined OCP formulation is effective, though cyproterone acetate 2 mg/ethinylestradiol 35 μg or drospirenone 3 mg/ethinylestradiol 20 μg have been specifically studied. 3
• OCPs increase circulating triglycerides and HDL cholesterol, but no evidence suggests increased cardiovascular events in PCOS compared to the general population. 1

Add metformin 500-2000 mg daily when:

• Insulin resistance or glucose intolerance is documented. 2
• Lifestyle modifications alone are insufficient for metabolic control. 2
• Patient has obesity or elevated cardiovascular risk factors. 2
• Metformin improves glucose tolerance and may positively impact risk factors for diabetes and cardiovascular disease. 1

For hirsutism specifically, combine OCP with spironolactone 50-200 mg daily:

• This combination provides superior results compared to monotherapy. 1, 3
• Spironolactone decreases testosterone production, competitively inhibits androgen receptor binding, and may inhibit 5α-reductase. 3
• Critical warning: Spironolactone is pregnancy category C and must be combined with reliable contraception due to risk of feminization of male fetuses. 3
• Monitor potassium in older patients, those with hypertension, diabetes, chronic kidney disease, or those taking ACE inhibitors, ARBs, or NSAIDs. 3
• Add topical eflornithine hydrochloride cream as adjunctive therapy—this is the only FDA-approved topical treatment for hirsutism. 1, 3
• Combine medical therapy with mechanical hair removal (plucking, shaving, waxing, electrolysis, or laser vaporization) for optimal results. 1, 3
• Expect 6-12 months for visible improvement due to hair growth cycles; treatment is palliative, not curative. 1, 3

For Women Attempting to Conceive

Treatment sequence: 1, 2

1. First-line: Clomiphene citrate (after weight control and exercise program)

   • Clomiphene citrate is recommended based on good and consistent scientific evidence for its effectiveness. 1, 4
   • Approximately 80% of women with PCOS ovulate on clomiphene, and half of those conceive. 1
   • Start on or about day 5 of the cycle. 4
   • Do not exceed recommended dosage and duration; limit to about six total cycles (including three ovulatory cycles). 1, 4

2. Second-line: Low-dose gonadotropin therapy (if clomiphene fails)

   • Use low-dose rather than high-dose gonadotropin therapy to induce high rates of monofollicular development with lower risk of ovarian hyperstimulation. 1

3. Adjunctive therapy: Metformin

   • Metformin improves ovulation frequency and appears safe during pregnancy. 1, 5
   • May reduce miscarriage risk in PCOS. 5
   • Do not use thiazolidinediones in pregnancy—their effects on early pregnancy are poorly documented. 1, 5

4. Surgical option: Laparoscopic ovarian drilling

   • The benefit and role remain undetermined according to ACOG. 1

Mandatory Metabolic Screening (All Patients, Regardless of Weight)

Screen all PCOS patients for metabolic abnormalities at diagnosis and at least annually: 2, 5

• Fasting glucose followed by 2-hour glucose tolerance test for type 2 diabetes screening. 2, 5
• Fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides). 2, 5
• Calculate BMI and waist-hip ratio. 2, 5
• Use ethnic-specific BMI and waist circumference categories for Asian, Hispanic, and South Asian populations who are at higher cardiometabolic risk. 2

Screen for mental health conditions:

• Women with PCOS have higher rates of depression, anxiety, and eating disorders. 2

Emerging Therapies

GLP-1 receptor agonists (liraglutide, semaglutide, exenatide) show promise for weight reduction and metabolic improvement when combined with lifestyle interventions. 2

• These agents appear superior to placebo for anthropometric outcomes. 2
• Consider for patients with obesity or elevated cardiovascular risk factors when lifestyle and metformin are insufficient. 2

Bariatric surgery is emerging as a potential adjunct therapy for PCOS patients with clinically severe obesity. 1

• Improvements in hirsutism, menstrual regularity, and fertility have been reported. 1
• Evidence quality is limited with high risk of bias, especially regarding reproductive outcomes including pregnancy. 1

Critical Pitfalls to Avoid

• Do not delay lifestyle intervention—it must be the foundation, not an afterthought. 2, 5
• Do not assume normal weight excludes metabolic dysfunction—screen all PCOS patients regardless of BMI. 2, 5
• Do not use spironolactone as monotherapy in patients attempting to conceive—use clomiphene citrate instead. 5, 3
• Do not use antiandrogens without concurrent contraception in women of reproductive potential. 3
• Do not exceed recommended clomiphene dosage and duration—limit to six total cycles. 1, 5, 4
• Do not expect rapid results with hirsutism treatment—set realistic expectations about the 6-12 month timeline. 3
• Do not use high-protein diets—concerns exist about adverse effects on renal function and lipids. 1