Endogenous oestradiol concentrations and cardiovascular outcomes in healthy older women: findings from the SHOW Study

OBJECTIVES: To determine the association between endogenous oestradiol concentrations and cardiovascular outcomes in healthy older women. METHODS: The Sex Hormones in Older Women Study was a prospective cohort sub-study of the Aspirin in Reducing Events in the Elderly trial. All participants were aged at least 70 years, with no previous major adverse cardiovascular events, and a life expectancy of at least 5 years. Women receiving sex steroids, anti-oestrogens, anti-androgens, or glucocorticoids were excluded. Oestradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Participants were categorised into three groups: oestradiol concentrations below the limit of detection (11 pmol/L), concentrations in tertiles 1-2, and in tertile 3. Associations were assessed using Cox proportional hazards regression adjusted for age, body mass index, smoking, alcohol consumption, diabetes, hypertension, dyslipidaemia, renal impairment, and treatment allocation. MAIN OUTCOME MEASURES: Major adverse cardiovascular events and all-cause mortality. RESULTS: Of the 5535 participants, 3661 (66.1%) had oestradiol concentrations below 11 pmol/L. Over median follow-ups of 4.5 and 4.6 years, respectively, 144 women experienced a first major adverse cardiovascular event, and 200 women died. With tertiles 1-2 as the reference, oestradiol concentrations below 11 pmol/L and in tertile 3 were not associated with the incidence of major adverse cardiovascular events (hazard ratio 1.11, 95% confidence interval 0.73-1.67, and 0.83, 95% confidence interval 0.43-1.60, respectively). Plasma oestradiol was not associated with all-cause mortality. CONCLUSION: Endogenous oestradiol concentrations were not independently associated with major adverse cardiovascular events or all-cause mortality in relatively healthy older women.