Higher Levels of Endogenous Estradiol are Associated with Frailty in Postmenopausal Women from the Toledo Study for Healthy Aging

Background: Adverse effects of higher endogenous estradiol (E2) levels on various clinical outcomes and on determinants of the frailty syndrome have recently been reported. However, there are no data about the potential relationship between E2 and frailty. We aimed to study the association between E2 levels and frailty among older postmenopausal women not taking hormonal therapy. Methods: We used data from the Toledo Study for Healthy Aging, a Spanish population-based cohort study. Frailty was defined according to Fried's approach. Multivariate odds ratios (OR) and 95% confidence intervals (CI) associated with E2 levels were estimated using polytomous logistic regression. Results: E2 levels decreased significantly with age and educational level, whereas they increased with body mass index, high-sensitivity C-reactive protein (hs-CRP), and impairment in Katz activities of daily living. Higher E2 levels were associated with the prevalence of frailty among women younger than 79 yr, but not in the oldest group (p interaction = 0.047). After adjustment, OR of frailty associated with a 1 SD increase of E2 was 1.51 (95% CI, 1.04-2.20; P = 0.03). We identified an interaction between E2 and hs-CRP on the prevalence of frailty (P value = 0.042). Women with both higher E2 and hs-CRP (defined as values into the upper tertile) had an age-adjusted OR of 4.2 (95% CI, 1.7-10.5; P = 0.002), compared with women with low levels of both E2 and hs-CRP. Conclusion: Higher E2 levels were associated with frailty in postmenopausal women. The synergism between higher E2 and hs-CRP levels suggests the existence of physiopathological mechanisms connecting inflammation and estrogen to frailty. (J Clin Endocrinol Metab 97: 2898-2906, 2012)