Context: The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied.
Objective: The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed.
Design: Prospective cohort.
Setting: A reproductive endocrinology clinic in a university-affiliated medical center.
Patients: One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled.
Intervention: Metformin was given daily for 24 months.
Main outcome measures: The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline.
Results: Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77).
Conclusions: Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.
Trial registration: ClinicalTrials.gov NCT00172523.