Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome

OBJECTIVE: We hypothesized that body mass index (BMI) and DNA variants would predict age at menarche in polycystic ovarian syndrome (PCOS). SUBJECTS: Subjects aged 18-45 years with PCOS defined by the National Institutes of Health criteria (n=522) and controls with regular menstrual cycles and no hyperandrogenism (n=472) were studied. METHODS: Age at menarche was compared between PCOS cases and controls and examined as a function of multiple parameters. RESULTS: There was a strong inverse relationship between BMI and age at menarche in PCOS (r=-0.32, p=5 x lO(-11)). The chromosome 6 rs7759938-T variant was associated with earlier age at menarche in women with PCOS (12.60 +/- 0.09 vs. 13.41 +/- 0.23 years; genotype TT vs. CC; p = 0.006). Age at menarche was predicted by PCOS status (beta = 0.512, p < 0.001), reported weight group at 10-14 years (beta = -0.432, p < 0.001), current BMI (beta = -0.0202, p = 0.01), and genotype (beta = 0.169, p = 0.02). CONCLUSIONS: Age at menarche in women with PCOS is influenced by BMI and genetic variants near LIN28B.