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. 2009 Oct;94(10):3806-15.
doi: 10.1210/jc.2009-0417. Epub 2009 Sep 8.

Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study

Peggy M Cawthon  1 , Kristine E Ensrud, Gail A Laughlin, Jane A Cauley, Thuy-Tien L Dam, Elizabeth Barrett-Connor, Howard A Fink, Andrew R Hoffman, Edith Lau, Nancy E Lane, Marcia L Stefanick, Steven R Cummings, Eric S Orwoll; Osteoporotic Fractures in Men (MrOS) Research Group
Collaborators, Affiliations

Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study

Peggy M Cawthon et al. J Clin Endocrinol Metab. 2009 Oct.

Abstract

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.

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Figures

Figure 1
Figure 1
Participants selected for cross-sectional and longitudinal analyses.
Figure 2
Figure 2
Restricted cubic spline plot of ORs for greater frailty status at baseline by level of bioavailable testosterone. Dotted vertical lines represent the quartile cut-points for bioavailable testosterone: Q1, ≤165.4 ng/dl; Q2, 165.4 to <201.5 ng/dl; Q3, 201.5 to <241.9 ng/dl; and Q4, ≥241.9 ng/dl. Gray dotted lines represent the 95% CI for the OR.
Figure 3
Figure 3
Predicted probability of frailty status at follow-up, by quartile of bioavailable testosterone and frailty status at baseline for a 73.4-yr-old man. Cut-points for quartiles of bioavailable testosterone: Q1, ≤165.4 ng/dl; Q2, 165.4 to <201.5 ng/dl; Q3, 201.5 to <241.9 ng/dl; and Q4, ≥241.9 ng/dl. Probabilities derived from a partial proportional odds model, with age and bioavailable testosterone meeting the proportionality assumption, and frailty status at baseline not meeting the proportional odds assumption. The age assumed for the model (73.4 yr) is the mean age of the population at baseline.
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References

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