Relationship between age at menarche and risk of glucose metabolism disorder: a systematic review and dose-response meta-analysis

Abstract Objective: Studies investigating the impact of age at menarche on glucose metabolism disorder have reached inconsistent conclusions, and a quantitative comprehensive assessment of the dose-response association between age at menarche and glucose metabolism disorder has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of glucose metabolism disorder by age at menarche. Methods: MEDLINE via PubMed and EMBASE databases were searched up to March 13, 2019. Restricted cubic splines were used to model the dose-response association. Results: Twenty-five publications (including 34 studies) were included in the meta-analysis. The summary risk ratios (RRs) and 95% confidence limit (CL) per 1-year increase in age at menarche were 0.98 (95% CL 0.98, 0.99) for type 2 diabetes mellitus (T2DM), 0.97 (95% CL 0.96, 0.99) for impaired fasting glucose (IFG), and 0.98 (95% CL 0.97, 0.99) for gestational diabetes mellitus (GDM). We identified linear negative correlations between age at menarche and T2DM ( P nonlinearity = 0.052) and IFG ( P nonlinearity = 0.145), a nonlinear dose-response between age at menarche and GDM ( P nonlinearity = 0.038). Conclusions: Older age at menarche (range 8-18 years old) is associated with reduced risk of glucose metabolism disorder. The strongest reduction in risk of GDM is observed at menarche age of 14.5 years.