Low Bioavailable Testosterone Linked to Frailty in Older Men

Megan Brooks

October 30, 2009

October 30, 2009 — Low levels of bioavailable testosterone are independently associated with a greater level of frailty in elderly men, according to results of a study appearing in the October issue of the Journal of Clinical Endocrinology and Metabolism.

However, as first author Dr. Peggy M. Cawthon noted in an email to Reuters Health, the causal association between low bioavailable testosterone and frailty "has yet to be proven in a randomized clinical trial. Thus, we suggest that the next step is to include assessment of frailty status in clinical trials of testosterone supplementation."

Dr. Cawthon from California Pacific Medical Center, San Francisco and colleagues note in their report that as men age, the prevalence of frailty in men increases and the levels of androgens fall. Yet, "little is known about the relation between these factors.”

To investigate, they assessed cross-sectional and longitudinal associations between frailty and sex hormones (estradiol, bioavailable estradiol, testosterone, bioavailable testosterone, and sex hormone binding globulin) in 1469 men who were at least 65 years old at baseline. The men were participants in the multicenter US observational Osteoporotic Fractures in Men (MrOS) study.

Frailty was assessed in all 1469 men at baseline and in 1245 men 4.1 years later using a standard scale. "For frailty assessment, we measured five areas: weakness (lowest 20% in grip strength), slowness (slow 20% in walking speed), activity level (lowest 20% by questionnaire), shrinking/sarcopenia (worst lean body mass for height and percent fat), and exhaustion (questionnaire)," Dr. Cawthon explained.

Men with three or more of these five factors were considered frail; those who met the criteria in one or two of these factors were considered intermediate, and men who did not meet the criteria for any of the factors were considered robust.

At baseline, 682 men (46.4%) were classified as robust, 675 (46.0%) as intermediate and 112 (7.6%) as frail.

Roughly 11% of men in the lowest quartile of bioavailable testosterone (<165 ng/dL) were frail at the baseline exam, compared with 5.4% in the highest quartile (241.9 ng/dL or greater).

In multivariate cross-sectional analyses, men in the lowest quartile of bioavailable testosterone had a 1.39-fold increased likelihood of greater frailty status compared to men in the highest quartile, the report indicates.

"This association persisted even after we took into account a variety of factors, including age and co-existing medical conditions," Dr. Cawthon said.

"There was also the suggestion of an association between bioavailable testosterone levels and frailty status measured about 4 years later,” she said, “suggesting that the association between bioavailable testosterone and frailty persisted over time."

More specifically, at the second assessment, 437 men (35.1%) were classified as robust, 517 (41.5%) were intermediate, 131 (10.5%) were frail, and 160 (12.9%) had died.

In age-adjusted longitudinal analyses, men in the lowest versus the highest quartile of bioavailable testosterone had a 1.51-fold increased likelihood of greater frailty status 4.1 years after baseline. However, this association was largely attenuated (OR, 1.32) on multivariate analysis.

The researchers did not see an association between frailty and any of the other hormones that they measured.

The mechanisms by which bioavailable testosterone may influence frailty status are not well known, Dr. Cawthon and colleagues note in their report. Declining levels of testosterone, they say, may contribute to muscle shrinking and weakness as well as a proinflammatory state, which has been linked to poor physical performance and frailty.

"Further research into the biological underpinnings of the bioavailable testosterone and frailty relationship is needed," the study team concludes.

J Clin Endocrinol Metab. 2009;94:3806-3815. Abstract

Reuters Health Information 2009. © 2009 Reuters Ltd.

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