What is the first line of treatment for Polycystic Ovary Syndrome (PCOS)?

First-Line Treatment for Polycystic Ovary Syndrome (PCOS)

Metformin should be initiated as the first-line medication for PCOS with metabolic features, at a dose of 500mg daily with meals, increasing gradually to 1000-1500mg daily in divided doses, while lifestyle modifications including 250 minutes/week of moderate-intensity physical activity and dietary changes should always form the foundation of treatment. 1

Treatment Algorithm for PCOS

Step 1: Initial Assessment and Lifestyle Modifications

• Implement lifestyle modifications as the foundation of all PCOS treatment:
  • 250 minutes/week of moderate-intensity physical activity
  • Energy deficit of 500-750 kcal/day
  • Low glycemic index diet rich in fiber and omega-3 fatty acids 1

Step 2: Pharmacological Treatment Based on Primary Symptoms

For Metabolic Features (insulin resistance, weight concerns):

• Metformin starting at 500mg daily with meals, gradually increasing to 1000-1500mg daily in divided doses 1
• Consider GLP-1 receptor agonists (liraglutide, semaglutide) for patients with significant weight concerns, as they may be more effective for weight loss than metformin 1

For Menstrual Irregularities/Hyperandrogenism:

• Combined oral contraceptives (COCs) are first-line therapy for:
  • Menstrual regulation
  • Reducing hyperandrogenism
  • Endometrial protection 1, 2
• Important caveat: COCs increase venous thromboembolism risk three to fourfold (up to 4 per 10,000 woman-years) 1, 2

For Hirsutism:

• Spironolactone 100 mg daily (visible improvement typically takes 6 months) 1

For Fertility Concerns:

• Clomiphene citrate is first-line for ovulation induction, starting on day 5 of the cycle (80% ovulation rate, 50% conception rate) 1, 3
• Letrozole is an effective alternative for ovulation induction 3

Special Considerations

Risk Assessment Before Starting COCs

• Evaluate for:
  • Age
  • Smoking status
  • Obesity
  • Glucose intolerance or diabetes
  • Hypertension
  • Dyslipidemia
  • Thrombophilia
  • Family history of venous thromboembolism 2, 4

Endometrial Protection

• For women not using COCs, oral micronized progesterone (200-300 mg daily for 12-14 days monthly) provides protection against endometrial hyperplasia 1

Monitoring and Follow-up

• Regular follow-up every 6 months to monitor:
  • Blood pressure
  • Lipid levels
  • Menstrual cyclicity
  • Weight changes
  • Metabolic parameters 1

Common Pitfalls to Avoid

1. Delaying treatment of metabolic features: Insulin resistance should be addressed early to prevent progression to diabetes and cardiovascular disease 1, 5

2. Prescribing COCs without risk assessment: Always evaluate thrombosis risk factors before starting hormonal contraceptives 2, 4

3. Overlooking endometrial protection: Women with irregular cycles need protection against endometrial hyperplasia 1

4. Focusing on single symptoms: PCOS requires comprehensive management of all presenting features 5

5. Missing red flags: Persistent abnormal uterine bleeding despite treatment, significant virilization, rapid symptom development, or worsening insulin resistance despite treatment require prompt evaluation 1

The American College of Obstetricians and Gynecologists emphasizes that treatment should address the patient's specific symptoms, including menstrual irregularities, hyperandrogenism, endometrial protection, and fertility concerns 1. While treatment can be tailored to the patient's predominant symptoms, metformin and lifestyle modifications form the cornerstone of first-line therapy for most patients with PCOS, particularly those with metabolic features.