Long-term efficacy of metformin in overweight-obese PCOS: longitudinal follow-up of retrospective cohort

OBJECTIVE: Long-term efficacy of metformin in polycystic ovarian syndrome (PCOS) apart from in those with impaired glucose tolerance or diabetes remains unproven. We aimed to evaluate the impact of metformin in overweight-obese patients with PCOS and normal baseline glycemic homeostasis. METHODS: A 10-year longitudinal follow-up of a retrospective cohort comprising 159 patients with PCOS defined by Rotterdam criteria, BMI ≥25 kg/m(2) and normal initial glucose homeostasis (age 28.4 ± 6.4 years, BMI 34.9 ± 6.6 kg/m(2)) that had been receiving metformin 1000 mg BID. Collection data contained 6085 time-points including anthropometric, hormonal and metabolic parameters. RESULTS: After the first year body mass (BM) decreased for 3.9 ± 6.8 kg (P < 0.001) and remained stable during the following 3 years. Menstrual frequency (MF) increased to 3.0 ± 3.9 bleeds/year (P < 0.001) after first year to over 11 bleeds/year in the following years. The total testosterone and androstenedione decreased to 15.4 ± 47.9% and 11.3 ± 46.4% within first year, with further decrease in total testosterone and androstenedione to 37.8 ± 61.8 and 24.8 ± 40.5% at the fifth year of the follow-up. The total conversion rate to prediabetes and diabetes was extremely low throughout observation period. Less than 25% of patients continued with metformin for more than 5 years with further dropout to only 6% on metformin therapy at the tenth year of follow-up. CONCLUSIONS: Long-term metformin treatment of overweight-obese women with PCOS and normal baseline glycemic homeostasis resulted in reduction and stabilization of BM, improvements of MF and androgen profile and low conversion rate to diabetes.