When is metformin (biguanide) prescribed for patients with Polycystic Ovary Syndrome (PCOS)?

Metformin Prescription Guidelines for PCOS

Metformin should be prescribed for PCOS patients who have insulin resistance, cardiometabolic risk factors, or anovulation not responding to first-line treatments, but should not be used as primary therapy for weight loss or hirsutism. 1

Indications for Metformin in PCOS

Metformin is indicated in the following specific scenarios:

1. Patients with insulin resistance markers:

   • Presence of acanthosis nigricans
   • Obesity (especially abdominal)
   • Abnormal glucose tolerance test results
   • Elevated fasting insulin levels

2. Cardiometabolic risk management:

   • Prediabetes or impaired glucose tolerance
   • Dyslipidemia (especially elevated triglycerides)
   • Metabolic syndrome features

3. Reproductive health:

   • Anovulation not responding to first-line treatments
   • As an adjunct to clomiphene citrate for ovulation induction
   • Menstrual irregularity, particularly in women with insulin resistance

When NOT to Use Metformin as First-Line

Metformin should not be used as primary therapy for:

• Weight loss (limited efficacy as standalone treatment)
• Hirsutism or acne (insufficient evidence for clinical improvement)
• Ovulation induction (clomiphene citrate is first-line)

Dosing and Administration

• Starting dose: 500 mg once daily
• Titration: Increase gradually over 2-4 weeks to minimize gastrointestinal side effects
• Target dose: 1500-2000 mg daily (divided doses)
• Duration: Long-term therapy often required for sustained benefits

Monitoring Parameters

• Baseline and periodic assessment of:
  • Fasting glucose and insulin levels
  • Oral glucose tolerance test (if indicated)
  • Lipid profile
  • Liver and kidney function tests
  • Menstrual pattern
  • Androgen levels (total testosterone, SHBG)

Special Considerations

Adolescents with PCOS

Metformin may be particularly beneficial in adolescents with PCOS who have obesity and glucose intolerance 1. Early intervention may help prevent progression of metabolic complications.

Pregnancy Considerations

• Metformin should be discontinued during pregnancy unless specifically indicated for diabetes management
• Women on metformin should receive preconception counseling due to potential for improved fertility 1, 2
• Metformin may reduce early pregnancy loss and preterm birth in some women with PCOS 3

Clinical Pearls and Pitfalls

• Common side effects: Gastrointestinal disturbances (nausea, diarrhea) - can be minimized with gradual dose titration and taking with meals
• Contraindications: Renal dysfunction, hepatic disease, alcoholism, acute illness with dehydration
• Drug interactions: Temporarily discontinue with radiocontrast procedures
• Expectations management: Benefits may take 3-6 months to become apparent; not all patients will respond

Algorithm for Metformin Use in PCOS

1. First step: Confirm PCOS diagnosis using Rotterdam criteria
2. Second step: Assess for insulin resistance markers and cardiometabolic risk
3. Third step: Initiate lifestyle modifications (diet, exercise) for all patients
4. Fourth step: Consider metformin if:
   • Insulin resistance is documented
   • Cardiometabolic risk factors are present
   • Menstrual irregularity persists despite lifestyle changes
   • Clomiphene citrate alone fails to induce ovulation in women seeking pregnancy

Metformin's efficacy in PCOS is most pronounced in women with documented insulin resistance, and its effects include improved insulin sensitivity, reduced androgen levels, and better menstrual regularity 4. The medication typically shows metabolic improvements within 4 weeks of initiation, but reproductive benefits may take longer to manifest 4, 5.