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=5x10(-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