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Low Serum Testosterone and Estradiol Predict Mortality in Elderly Men

The Wallenberg Laboratory for Cardiovascular Research (A.T.), Institute of Medicine, Sahlgrenska Academy, and Center for Bone Research at the Sahlgrenska Academy (L.V., D.M., C.O.), Departments of Internal Medicine and Geriatrics, University of Gothenburg, S-413 45 Gothenburg, Sweden; Laboratory of Molecular Endocrinology and Oncology (F.L.), Laval University Hospital Research Center and Laval University, Québec, Canada G5Y 0H1; Clinical and Molecular Osteoporosis Research Unit (M.K.K.), Department of Clinical Sciences, Lund University, S-221 00 Lund, Sweden; Department of Orthopaedics (M.K.K.), Malmö University Hospital, SE-205 02 Malmö, Sweden; and Department of Medical Sciences (O.L.), University of Uppsala, SE-751 05 Uppsala, Sweden

Address all correspondence and requests for reprints to: Åsa Tivesten, Wallenberg Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: asa.tivesten{at}medic.gu.se.

Context: Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging, but previous studies report conflicting evidence about testosterone levels and male mortality. No large prospective cohort study has determined a possible association between serum estradiol and mortality in men.

Objective: The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality in elderly men.

Design, Setting, and Participants: We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospective population-based MrOS Sweden cohort (n = 3014; mean age, 75 yr; range, 69–80 yr).

Main Outcome Measure: All-cause mortality by serum testosterone and estradiol levels.

Results: During a mean follow-up period of 4.5 yr, 383 deaths occurred. In multivariate hazards regression models, low levels (within quartile 1 vs. quartiles 2–4) of both testosterone [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.29–2.12] and estradiol (HR, 1.54; 95% CI, 1.22–1.95) associated with mortality. A model including both hormones showed that both low testosterone (HR, 1.46; 95% CI, 1.11–1.92) and estradiol (HR, 1.33; 95% CI, 1.02–1.73) predicted mortality. Risk of death nearly doubled (HR, 1.96; 95% CI, 1.46–2.62) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2–4 of both hormones.

Conclusions: Elderly men with low serum testosterone and estradiol have increased risk of mortality, and subjects with low values of both testosterone and estradiol have the highest risk of mortality.