Relationship between higher estradiol levels and 9-year mortality in older women

Marcello Maggio, Gian Paolo Ceda, Fulvio Lauretani, Stefania Bandinelli, Carmelinda Ruggiero, Jack M. Guralnik, E. Jeffrey Metter, Shari M. Ling, Giuseppe Paolisso, Giorgio Valenti, Anne R. Cappola, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1810-1815
Number of pages6
JournalJournal of the American Geriatrics Society
Issue number10
StatePublished - 2009
Externally publishedYes


  • Estradiol
  • Mortality
  • Older postmenopausal women

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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