Relationship Between Higher Estradiol Levels and 9‐Year Mortality in Older Women: The Invecchiare in Chianti Study

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Abstract
OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9‐year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).DESIGN: Population‐based study of persons living in the Chianti geographic area (Tuscany, Italy).SETTING: Community.PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C‐reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P=.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P<.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P<.001).Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P=.04) and not predictive of death for less than 5 years (P=.78).CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.