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Sex Hormones and Frailty in Older Men: The Osteoporotic Fractures in Men (MrOS) Study

Research Institute (P.M.C., S.R.C.), California Pacific Medical Center, San Francisco, California 94107-1728; University of Minnesota and Minneapolis VA Medical Center (K.E.E.), Minneapolis, Minnesota 55417; Department of Family and Preventive Medicine (G.A.L., E.B.-C.), University of California at San Diego, La Jolla, California 92103; University of Pittsburgh (J.A.C.), Pittsburgh, Pennsylvania 15260; Department of Medicine (T.-T.L.D.), Columbia University, New York, New York 10027; University of Minnesota (H.A.F.), Geriatric Research Education and Clinical Center, VA Medical Center, and Center for Chronic Disease Outcomes Research, VA Medical Center, Minneapolis, Minnesota 55417; Veterans Affairs Palo Alto Health Care System and Stanford University Medical Center (A.R.H.), Palo Alto, California 94305; Center for Health and Medical Research (E.L.), Hong Kong, China; Department of Medicine (N.E.L.), University of California at Davis Medical School, Sacramento, California 95817; Stanford Prevention Research Center (M.L.S.), Stanford School of Medicine, Stanford, California 94305; and Bone and Mineral Unit (E.S.O.), Oregon Health and Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Peggy Mannen Cawthon, Associate Scientist, California Pacific Medical Center Research Institute, San Francisco Coordinating Center, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, California 94107-1728. E-mail: pcawthon{at}sfcc-cpmc.net.

Context: As men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors.

Objective: The aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status.

Design and Setting: The Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers.

Participants: A total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later.

Main Outcome Measure: Proportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods.

Results: In cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment.

Conclusions: Low levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.