End of Frailty and Shrinking with Aging

Frailty is defined as a state where older individuals are particularly susceptible to external stressors. The phenotype of frailty is mainly comprised of five domains: weakness (grip strength), shrinking/sarcopenia (weight loss), slowness (walking speed), low activity level, and exhaustion. The increased prevalence of frailty and the age-related decline in physical function parallel the androgen decline seen in older men. Thus it has been suggested that there may be an association between frailty and low sex hormone levels in older men. This article aims to describe the cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone, and sex hormone-binding globulin (SHBG) with frailty in community-dwelling older men using data from the Osteoporotic Fractures in Men (MrOS) study.
The MrOS study initially recruited 5995 community-dwelling men aged 65 years and older from six U.S. clinical centers for a baseline visit between March 2000 and April 2002. A random sample of 1602 was selected for assessment of sex hormone levels in 2007-2008 using previously stored serum from the baseline exam in 2000-2002. At baseline, 682 (46.4%) men were robust, 675 (46.0%) were classified as frail. Men in the lowest quartiles of bioavailable testosterone tended to be older and to have higher BMI and greater body fat than those with higher levels of bioavailable testosterone. They were also less likely to be married, have at least a college education, and report excellent or a good health status. These men were also more likely to have lower physical activity, to walk more slowly, to report more medical conditions, and to have lower grip strength and leg power than men with higher bioavailable testosterone levels.
To sum it all up, lower bioavailable testosterone levels were associated with an increased likelihood of worse frailty status in cross sectional analyses, independent of potentially confounding factors. This article provides further evidence that frailty is an outcome that should be considered in clinical trials of testosterone supplementation or other agents that alter sex hormone pathways. However, interventions that do not alter the non-SHBG-bound fraction of testosterone or its bioavailability may not have an impact on frailty status.
Peggy M. Cawthon, 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 for the Osteoporotic Fractures in Men (MrOS) Research Group1
Sex Hormones and Frailty in Older Men: The Osteoporotic Fractures in Men (MrOS) Study
The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 3806-3815 – Copyright © 2009 by The Endocrine Society