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      Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis

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          Abstract

          <div class="section"> <a class="named-anchor" id="s1"> <!-- named anchor --> </a> <h5 class="section-title" id="d7214577e187">Background</h5> <p id="d7214577e189">Despite the high prevalence of frailty among patients receiving hemodialysis, few preventable or treatable contributing causes have been identified. Hypogonadism is also common in this population and low serum testosterone concentrations share several clinical phenotypes with frailty. We hypothesized that low serum testosterone concentrations would be associated with frailty and several of its individual components. </p> </div><div class="section"> <a class="named-anchor" id="s2"> <!-- named anchor --> </a> <h5 class="section-title" id="d7214577e192">Methods</h5> <p id="d7214577e194">We used data from 440 men from A Cohort Study To Investigate the Value of Exercise in ESRD/Analysis Designed to Investigate the Paradox of Obesity and Survival in ESRD, a longitudinal study that recruited participants from 14 dialysis centers in Atlanta, GA and the San Francisco, CA Bay Area from 2009 to 2011. We assessed frailty using the Fried Frailty Phenotype. We examined the association between free testosterone (as a continuous and dichotomous variable) and frailty, individual frailty components, sarcopenia, lower extremity function and muscle mass estimation by creatinine and body impedance spectroscopy over 12 months using generalized estimating equations. </p> </div><div class="section"> <a class="named-anchor" id="s3"> <!-- named anchor --> </a> <h5 class="section-title" id="d7214577e197">Results</h5> <p id="d7214577e199">The mean age was 56.1 ± 14.2 years and 27% were white. A 50% lower concentration of free testosterone was associated with 1.40-fold higher odds of being frail [95% confidence interval (CI) 1.05–1.53] and 1.40-fold higher odds of becoming frail over 12 months (95% CI 1.07–1.73). This association was mainly due to an association with two components of frailty: grip strength and gait speed. In addition, 50% lower free testosterone concentration was associated with a 1.55-fold higher odds of having sarcopenia (95% CI 1.09–2.02) and 1.72-fold higher odds for developing sarcopenia (95% CI 1.13–2.33) as well as with lower muscle mass and a decrease in muscle mass over 12 months as estimated by serum creatinine and by bioelectrical impedance spectroscopy. </p> </div><div class="section"> <a class="named-anchor" id="s4"> <!-- named anchor --> </a> <h5 class="section-title" id="d7214577e202">Conclusion</h5> <p id="d7214577e204">Serum free testosterone concentration was associated with frailty, physical function, sarcopenia and muscle mass as well as with changes in these outcomes over 12 months. Testosterone replacement may be a feasible therapeutic target toward prevention of frailty, although clinical trials are needed to test this possibility. </p> </div>

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          Most cited references21

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          Adverse events associated with testosterone administration.

          Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.) 2010 Massachusetts Medical Society
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            Effects of Testosterone Treatment in Older Men.

            Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.
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              Significance of frailty among dialysis patients.

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                Author and article information

                Journal
                Nephrology Dialysis Transplantation
                Oxford University Press (OUP)
                0931-0509
                1460-2385
                May 2019
                May 01 2019
                August 01 2018
                May 2019
                May 01 2019
                August 01 2018
                : 34
                : 5
                : 802-810
                Affiliations
                [1 ]Department of Medicine, Division of Endocrinology, University of California, San Francisco, San Francisco, CA, USA
                [2 ]Department of Medicine, Division of Nephrology, University of California, Davis, Davis, CA, USA
                [3 ]Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
                [4 ]Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA
                [5 ]Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, CA, USA
                [6 ]San Francisco VA Medical Center, Department of Medicine, Division of Nephrology, San Francisco, CA, USA
                Article
                10.1093/ndt/gfy252
                6503299
                30085235
                ebae539e-7764-4449-b837-e4b9daba7b2f
                © 2018

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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