Early menarche, nulliparity and the risk for premature and early natural menopause.
Level 3 - non-randomized controlled study
Pooled individual-participant analysis of observational studies
PubMed 28119483 · doi:10.1093/humrep/dew350
What was done
A pooled analysis of 51,450 postmenopausal women from nine observational studies across the UK, Scandinavia, Australia, and Japan (InterLACE consortium). The authors evaluated associations of age at menarche (categorized as ≤11, 12, 13, 14, and ≥15 years) and parity (0, 1, and ≥2 children) with age at natural final menstrual period (FMP), categorized as premature (<40 years), early (40–44 years), 45–49, 50–51, 52–53, and ≥54 years. Relative risk ratios (RRR) and 95% confidence intervals were estimated using multivariate multinomial logistic regression models adjusted for within-study correlation.
What was found
Median age at natural FMP was 50 years (IQR 48–53 years), with 2% of women experiencing premature menopause and 7.6% early menopause. Early menarche (≤11 vs. 12–13 years) was associated with higher risk of premature menopause (RRR 1.80, 95% CI 1.53–2.12) and early menopause (RRR 1.31, 95% CI 1.19–1.44). Nulliparity was associated with increased risk of premature menopause (RRR 2.26, 95% CI 1.84–2.77) and early menopause (RRR 1.32, 95% CI 1.09–1.59). Women with both early menarche (≤11 years) and nulliparity had an over 5-fold increased risk of premature menopause (RRR 5.64, 95% CI 4.04–7.87) and a 2-fold increased risk of early menopause (RRR 2.16, 95% CI 1.48–3.15) compared with women with menarche at ≥12 years and ≥2 children.
Why it matters
This large pooled study demonstrates that early menarche and nulliparity independently and synergistically increase the risk of premature and early natural menopause. These reproductive markers could help identify women who may benefit from earlier monitoring and preventive strategies for chronic disease risks associated with early estrogen deficiency.
Limits
Most contributing studies (except birth cohorts) relied on retrospective self-reporting of age at menarche, creating potential recall bias. As an observational analysis, residual confounding cannot be ruled out, and the abstract does not specify the full set of covariates adjusted for in the multivariable models.
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