Reproductive lifespan and incident stroke risk among post-menopausal women: Is it time for sex-specific risk prediction tools?

Cardiovascular disease (CVD) remains the leading cause of death among women, and post-menopausal women suffer from higher mortality attributable to cardiovascular events compared with men of similar age [ [1] Maffei S. Guiducci L. Cugusi L. et al. Women-specific predictors of cardiovascular disease risk - new paradigms. Int. J. Cardiol. 2019; 286: 190-197 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ]. Women-specific risk factors of preventable CVD, including age of menarche and menopause, have been a focus of recent investigations in attempts to minimize this gap. Early-onset menopause is now recognized as a CVD risk-enhancing factor in recent guidelines [ [2] Cho L. Davis M. Elgendy I. et al. Summary of updated recommendations for primary prevention of cardiovascular disease in women: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2020; 75: 2602-2618 Crossref PubMed Scopus (39) Google Scholar ]. Owing to the protective effect of endogenous estrogen, several studies have examined the association between the reproductive lifespan (i.e., defined as the difference between age of menopause and age of menarche) and cardiovascular events. These studies have demonstrated that a shorter reproductive lifespan is associated with higher risk of cardiovascular events including ischemic stroke [ 3 Alonso de Leciñana M. Egido J.A. Fernández C. et al. Risk of ischemic stroke and lifetime estrogen exposure. Neurology. 2007; 68: 33-38 Crossref PubMed Scopus (69) Google Scholar , 4 Mansoor H. Elgendy I.Y. Segal R. Hartzema A. Duration of reproductive years and the risk of cardiovascular and cerebrovascular events in older women: Insights from the National Health and Nutrition Examination Survey. J. Women's Health (Larchmt). 2017; 26: 1047-1052 Crossref PubMed Scopus (18) Google Scholar , 5 Ley S.H. Li Y. Tobias D.K. et al. Duration of reproductive life span, age at menarche, and age at menopause are associated with risk of cardiovascular disease in women. J. Am. Heart Assoc. 2017; 6e006713https://doi.org/10.1161/JAHA.117.006713 Crossref PubMed Scopus (68) Google Scholar ]. However, these studies did not take into consideration other factors that influence endogenous estrogen production such as pregnancy and breast feeding as well as exogenous hormonal sources as oral contraceptive pills (OCP) and menopausal hormone therapy (MHT).