Abstract
Background: Despite previous studies exploring female reproductive factors, early menarche and its impact on stroke risk remains under-reported. This systematic review seeks to further explore this correlation. Methods: PubMed, SCOPUS and EMBASE databases were systematically reviewed for studies reporting long-term incidence and odds of stroke in patients who had menarche at an early age vs. menarche at a normal age. Random effects models were used for the meta-analysis and subgroup analysis. I2 statistics were used to identify substantial (>75%) heterogeneity. A sensitivity analysis was performed using the leave-one-out method. Results: Ten prospective studies with a total of 1,971,454 patients were included and the odds of stroke were evaluated for patients with early menarche vs controls. Overall unadjusted odds for stroke with early menarche was 1.14 (95%CI 1.08 -1.20, p<0.01, I2=0%). (Fig.1b) Adjusted odds ratio; [aOR 1.22 (95% CI 1.08 - 1.39), I2=86.85%, p<0.01]. (Fig. 1a) Leave-one-out sensitivity analysis confirmed equivalent results. (Fig.1c) On subgroup analysis, studies from the USA with early menarche had the highest stroke risk of countries reported (1.48, 95%CI 1.04-2.09) followed by China (1.26, 95% CI 1.09-1.45) and the UK (1.08, 95%CI 0.96-1.21). There was stronger stroke association with mean/median age cohort ≥ 60 yrs (1.43, 95% CI 1.08 - 1.89) vs <60 yrs (1.18, 95% CI 1.03 - 1.36). Conclusions: This meta-analysis revealed that early menarche is associated with a higher risk of stroke with the strongest association in women from the USA.
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