Age at menarche not linked to increased risk of cardiometabolic diseases in adulthood

Evidence concerning the causal effect of age at menarche (AAM) on the risk of cardiometabolic diseases in adult life is lacking, a recent study has shown. The associations seen in epidemiological studies between AAM and cardiometabolic traits appear to be largely facilitated through excessive adiposity.

Genome-wide association study (GWAS) summary statistics from the Diabetes Genetics Replication and Meta-analysis consortium (n=159,208) for type 2 diabetes (T2D) and the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics consortium (n=184,305) for CAD were used to carry out a two-sample Mendelian randomization (MR) analysis.

The authors used 122 instrumental variables (IVs) extracted from a published GWAS meta-analysis incorporating 182,416 women to establish the causal effect of AAM on cardiometabolic diseases, with childhood and adult body mass index (BMI) as potential confounders. They also conducted sensitivity analyses to detect the pleiotropy of the IVs.

MR analyses revealed an association between later AAM and a reduced risk of CAD (odds ratio, 0.92, 95 percent confidence interval, 0.88–0.96; p=2.06 × 10^–4) in adults. AAM also correlated with lower blood levels of log fasting insulin, log homeostatic model assessment of insulin resistance (HOMA-IR), log HOMA of β-cell function (HOMA-B), triglycerides and diastolic blood pressure, but higher blood level of high-density lipoprotein.

However, these associations substantially decreased after excluding BMI-related variants. Furthermore, MR analyses offered little evidence on the causal effect between AAM and T2D.

“We propose adiposity might be a primary target in future intervention strategy,” the authors said.