Age at menarche and risks of all-cause and cardiovascular death: a systematic review and meta-analysis

Abstract

We conducted a systematic review and meta-analysis to investigate the associations between menarcheal age and all-cause and cardiovascular death. Medline, Embase, Scopus, and Web of Knowledge were searched for articles published prior to March 2013 reporting on the associations between menarcheal age and death from all causes or from cardiovascular disease (total cardiovascular disease, ischemic heart disease (IHD), and stroke) in adult women. Nine articles were eligible for inclusion; these reported 5 estimates each for death from all causes and total cardiovascular death, 6 estimates for IHD, and 7 estimates for death from stroke. Our meta-analysis showed that each 1-year increase in age at menarche was associated with a 3% lower relative risk of death from all causes (pooled hazard ratio = 0.97, 95% confidence interval: 0.96, 0.98) with low heterogeneity (I(2) = 32.2%). Meta-analysis of 2 cohorts showed a higher risk of death from all causes for women who experienced early menarche (at <12 years of age) versus "not early" menarche (at ≥ 12 years of age) (pooled hazard ratio = 1.23, 95% confidence interval: 1.10, 1.38; I(2) = 0%). An inverse association between age at menarche and death from IHD was observed only among nonsmoking populations or populations with low prevalence of smoking. We found no evidence of association between age at menarche and death from all cardiovascular diseases or stroke. Early menarche was consistently associated with higher risk of death from all causes. Further studies are needed to clarify the role of menarcheal age on cardiovascular outcomes and to investigate the potential modifying role of smoking.

Keywords: cardiovascular disease; death rate; menarche; mortality; puberty.

Figure 1.

Flow diagram showing the search strategy used in the current review.

Figure 2.

Forest plot displaying a random-effects meta-analysis of the adjusted hazard ratios (HRs) for death from all causes associated with a 1-category (usually corresponding to a 1-year) increase in menarcheal age. Boxes represent the hazard ratios for each individual study with the size of the box reflecting the weight assigned to the study. Dotted vertical line represents the combined estimate. The width of the diamond illustrates the 95% confidence intervals (CIs) around the combined estimate.

Figure 3.

Forest plot displaying a random-effects meta-analysis of the adjusted hazard ratios (HRs) of death from all causes for the comparison between women with early menarche (at <12 years of age) and “not early” menarche (at ≥12 years of age). Boxes represent the hazard ratios for each individual study with the size of the box reflecting the weight assigned to the study. Dotted vertical line represents the combined estimate. The width of the diamond illustrates the 95% confidence intervals (CIs) around the combined estimate.

Figure 4.

Forest plot displaying a random-effects meta-analysis of the adjusted hazard ratios (HRs) of death from all causes comparing women in the earliest versus the median menarcheal age group. Boxes represent the hazard ratios for each individual study with the size of the box reflecting the weight assigned to the study. Dotted vertical line represents the combined estimate. The width of the diamond illustrates the 95% confidence intervals (CIs) around the combined estimate.

Figure 5.

Adjusted hazard ratios (HRs) (on a log scale) of death from all causes across categories of age at menarche in completed whole years from studies by A) Jacobsen et al. (14), B) Lakshman et al. (19), C) Tamakoshi et al. (15), and D) Jacobsen et al. (18). Triangles depict reference categories. Bars, 95% confidence intervals.

Figure 6.

Forest plot of the adjusted hazard ratio (HR) for ischemic heart disease, stroke, and total cardiovascular disease (CVD) death comparing women in the earliest versus the median menarcheal age group. Weights are from a random-effects model. Boxes represent the hazard ratios for each individual study with the size of the box reflecting the weight assigned to the study. Dotted vertical line represents the combined estimate. The width of the large diamonds illustrates the 95% confidence intervals (CIs) around the combined estimate.