Long-term health outcomes of early menarche in women: an umbrella review.

Abstract

There is limited comprehensive evidence on the potential association between early menarche and subsequent health outcomes. To evaluate the existing evidence for the association of early menarche with later health outcomes and assesse the strength and validity of the evidence for these associations. Umbrella review. We searched PubMed, Web of Science, Embase, CINAHL, Cochrane Database of Systematic Reviews and Google Scholar, and manually screened retrieved references to find systematic reviews and meta-analyses from inception to July 2021. Early menarche was defined by taking into account ethnicity and birth year, and the outcomes were long-term consequences in adulthood. Thirteen reviews encompassing 283 original articles and over 6.8 million participants from 39 countries across 5 continents were included. In categorical outcomes, early menarche was associated with metabolic syndrome (n = 37543 pooled adjusted relative risk [aRR] 1.56, 95% confidence interval (CI) 1.33, 1.83; high certainty [Hi]), endometrial cancer (n = 874 188, aRR 1.40, 95% CI 1.17, 1.68; Hi), type 2 diabetes mellitus/impaired glucose tolerance (n = 1185444, aRR 1.30, 95% CI 1.19, 1.42; Hi), breast cancer (n = 103574, aRR 1.19, 95% CI 1.06, 1.33; Hi), death from all causes (n = 152747, aRR 1.11, 95% CI 1.03, 1.19; Hi), obesity (n = 54006, aRR 1.68, 95% CI 1.53, 1.84; moderate certainty [Mod]), gestational diabetes mellitus (n = 48535, aRR 1.32, 95% CI 1.09, 1.58; Mod), hypertension (n = 1682689, aRR 1.24, 95% CI 1.20, 1.29; Mod), endometriosis (n = 885390, aRR 1.22, 95% CI 1.09, 1.37; Mod), ovarian cancer (n = 1022451, aRR 1.17, 95% CI 1.04, 1.31; Mod) and asthma (n = 22859, aRR 1.31, 95% CI 1.09, 1.57; low certainty [Lo]). For continuous outcomes, early menarche was associated with increased body mass index (BMI) in adults ≥40 years of age (n = 121943, adjusted pooled standardized mean difference [aSMD] 0.30, 95% CI 0.28, 0.32; Mod), BMI in adults <40 years of age (n = 124728, aSMD 0.39, 95% CI 0.36, 0.43; Mod), serum fasting insulin level (n = 17020, aSMD 0.52, 95% CI 0.48, 0.57; Mod) and homeostatic model assessment of insulin resistance (n = 7925, aSMD 0.27, 95% CI 0.19, 0.35; Mod). We found varied levels of evidence for the association between early menarche and the development of subsequent health problems. Our results recommend that physicians should pay attention to these associations, as early menarche can be a potential indicator of metabolic disorders and female-specific cancer and cause death in women.