The association between age at menarche and infertility: a systematic review and meta-analysis of observational studies.

Abstract

Objective: Both early and late age at menarche have been associated with various health issues and may influence the risk of infertility. This present study investigated the relationship between age at menarche and infertility risk.

Methods: This study follows PRISMA guidelines. Databases including PubMed, Scopus, Web of Science, Embase, and Cochrane were searched in December 2024. Odds ratios with 95% confidence intervals were estimated using a random-effects model. Heterogeneity was assessed with the I² index and chi-square, and publication bias was evaluated using Egger's test and a funnel plot. Sensitivity analysis and meta-regression examined study impact and variable influence on heterogeneity.

Results: Out of 7,267 articles screened, 18 primary studies were included, yielding 21 pieces of evidence. The odds ratio (OR) for infertility in the late menarche group compared to the normal menarche group was 1.44 (95% CI: 0.98-2.10), while the OR for the early menarche group versus the normal menarche group was 0.98 (95% CI: 0.68-1.42). Additionally, the OR for infertility in the early menarche group compared to the late menarche group was 0.77 (95% CI: 0.55-1.06). For primary infertility, the OR for the late menarche group relative to the normal menarche group was 1.98 (95% CI: 1.02-3.85), whereas the OR for the early menarche group compared to the late menarche group was 0.59 (95% CI: 0.36-0.97).

Conclusion: Although the overall meta-analysis lacked statistical significance, subgroup analysis revealed a notable association between late menarche and primary infertility. Women with late menarche had higher odds of infertility, supporting a dose-responsive relationship. The observed 44% increase in infertility odds highlights late menarche as a potential risk factor, warranting further investigation into its implications for reproductive health.