Age at menarche and the future risk of gestational diabetes: a systematic review and dose response meta-analysis

Published studies show an inconsistent association between age at menarche and the subsequent risk of developing gestational diabetes mellitus when pregnant. This systematic review and meta-analysis was performed to clarify any trends in this association in published observational population studies. We searched online databases for relevant studies, entered into them up until June 21st 2017. Five eligible studies were found and a pooled random effects dose response meta-analysis of results from these was conducted. This included coverage of 58,133 pregnancies, from which 3,035 women developed gestational diabetes. There was evidence of a non-linear association between age at menarche and gestational diabetes (overall p=1.4x10(-8); p for non-linearity=2.4x10(-4)), along with evidence of relatively low heterogeneity (I-2=25.5%). The largest predicted risk of gestational diabetes was associated with having a low age at menarche; the mean (95% confidence interval) risk relative to that associated with menarche at age 13years being: 9years 2.0 (1.6, 2.4), 10years 1.6 (1.4, 1.9), 11years 1.3 (1.2, 1.4), 12years 1.1 (1.1, 1.1), 13years was the reference, 14years 1.0 (1.0, 1.0), 15years 1.1 (0.9, 1.2), 16years 1.1 (0.9, 1.4). There was evidence of potential publication bias, such that the maximal true relative risk of gestational diabetes, associated with an age at menarche of 9 years, may be closer to 1.6 than 2. Nevertheless, the curvilinear relationship between age at menarche and the future risk of gestational diabetes in pregnancy appears robust.