What is the role of metformin (biguanide) in the treatment of Polycystic Ovary Syndrome (PCOS)?

Role of Metformin in Polycystic Ovary Syndrome (PCOS)

Metformin is recommended for PCOS patients who have cardiometabolic features such as abdominal obesity and insulin resistance, as it improves insulin sensitivity, menstrual regularity, and androgen levels, particularly in those with obesity or insulin resistance. 1, 2

Indications for Metformin in PCOS

Metformin should be used in PCOS patients with:

• Insulin resistance or impaired glucose tolerance
• Metabolic syndrome features (abdominal obesity, dyslipidemia, hypertension)
• Menstrual irregularities (when combined with other treatments)
• Anovulation in women attempting to conceive (as an adjunct therapy)

Mechanism of Action

Metformin works in PCOS by:

• Decreasing hepatic glucose output
• Enhancing insulin sensitivity in liver and muscle tissue
• Reducing compensatory hyperinsulinemia
• Indirectly lowering circulating androgen levels
• Improving glucose tolerance

Clinical Benefits

Metabolic Benefits

• Improves insulin sensitivity and reduces insulin resistance 3
• Maintains or improves glucose tolerance over time 1
• May have positive impacts on cardiovascular risk factors 1
• Decreases LDL cholesterol and triglyceride levels 4

Reproductive Benefits

• Improves frequency of ovulation 1, 2
• Restores menstrual cyclicity, particularly in insulin-resistant women 5
• Reduces androgen levels (testosterone, free androgen index) 4
• May enhance fertility when combined with other treatments 3

Limitations of Metformin

Metformin is not effective as:

• First-line therapy for weight loss
• Primary treatment for hirsutism or acne
• First-line therapy for ovulation induction in women seeking pregnancy (clomiphene citrate is preferred) 1

Dosing and Administration

• Weight-based dosing: 1000-1700 mg daily 4
• Start at lower doses and titrate up to minimize gastrointestinal side effects
• Continue long-term for sustained benefits

Monitoring and Follow-up

• Assess menstrual cyclicity every 1-3 months
• Monitor metabolic parameters (fasting glucose, lipid panel) annually
• Evaluate ovulatory function in women attempting conception
• Screen for contraindications: renal dysfunction, hepatic disease, hypoxemic conditions

Special Considerations

Pregnancy

• May reduce early pregnancy loss and preterm birth 3
• Should not be used during pregnancy without specific indications
• Requires preconception counseling as it may increase fertility and pregnancy risk 1

Contraindications

• Impaired renal function
• Known hepatic disease
• Hypoxemic conditions
• Severe infections
• Alcohol abuse
• Should be temporarily discontinued during acute illness with dehydration 1

Treatment Algorithm

1. First-line approach: Lifestyle modifications (weight loss and exercise)
2. For insulin resistance/metabolic features: Add metformin
3. For menstrual irregularities:
   • If contraception needed: Combined oral contraceptives
   • If insulin resistance present: Add metformin
4. For fertility:
   • First-line: Clomiphene citrate
   • If insulin resistance present: Consider adding metformin
   • If clomiphene fails: Low-dose gonadotropins

Common Pitfalls

• Using metformin as primary therapy for hirsutism (combination therapy with antiandrogens and ovarian suppression is more effective)
• Expecting immediate results (metabolic improvements may begin within 4 weeks, but reproductive benefits may take 3-6 months)
• Failing to discontinue during acute illness with dehydration (risk of lactic acidosis)
• Not providing contraception counseling (metformin may restore ovulation and increase pregnancy risk)

Metformin remains a valuable tool in PCOS management, particularly for women with insulin resistance, but should be used as part of a comprehensive treatment plan tailored to address the specific manifestations of PCOS in each patient.