Association of the length of oestrogen exposure with risk of incident stroke in postmenopausal women: Insights from a 20-year prospective study

Background: To examine the relationship between the length of oestrogen exposure and risk of incident stroke. Also, the additive value of each model was compared for assessing oestrogen exposure and stroke risk in postmenopausal women. Study design and setting: Prospective study of 5632 post-menopausal women without a prior history of stroke from 1996 through 2016 in Australian Longitudinal Study on Women's Health. Data on surrogate measures of oestrogen exposure were used to derive five indices of oestrogen exposure including reproductive lifespan (RLS) (age at menopause-age at menarche), endogenous oestrogen and total oestrogen exposure (which included menopausal hormone therapy (MHT use)). The relationships between the length of oestrogen exposure (quartiles) and incident stroke events were examined using multivariable adjusted Cox proportional hazard regression and their predictive accuracy were compared using area under the Receiver Operating Characteristic Curve. Results: The mean (SD) for RLS was 37.9(4.3) years. A shorter RLS (≤34 years) was associated with a higher risk of incident stroke after adjustment (HR: 1.85, 95%CI: 1.08, 3.15), compared with 38–40 years. There was 7% decrease in risk of stroke per 1-year increase in RLS (HR: 0.93, 95%CI: 0.89, 0.97). Even though the combination of endogenous oestrogen and exogenous hormones aimed to provide more accurate length of oestrogen exposure, the results showed that each model had similar goodness of fit and did not improve the model of just using RLS as a predictor of incident stroke. Conclusions: A shorter RLS (≤34 years) was associated with higher risk of incident stroke compared to medium RLS. Endogenous oestrogen and of total oestrogen exposure (which included MHT use) did not improve the model of just using RLS as a predictor of incident stroke.