Testosterone Supplementation May Increase Lean Body Mass in Older Men

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Testosterone Supplementation May Increase Lean Body Mass in Older Men CME

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD
Disclosures
Release Date: January 2, 2008; Valid for credit through January 2, 2009
Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians


January 2, 2008 — Testosterone supplementation for 6 months did not affect functional status or cognition in older men with low-normal testosterone levels, but it increased lean body mass and had mixed metabolic effects, according to the results of a double-blind, randomized controlled trial reported in the January 2 issue of the Journal of the American Medical Association.

"Serum testosterone levels decline significantly with aging," write Marielle H. Emmelot-Vonk, MD, from the University Medical Center Utrecht in the Netherlands, and colleagues. "Decline in testosterone is associated with many symptoms and signs of aging such as a decrease in muscle mass and muscle strength, cognitive decline, a decrease in bone mass, and an increase in (abdominal) fat mass. . . . Testosterone supplementation to older men might beneficially affect the aging processes."

From January 2004 to April 2005, a total of 237 healthy men, aged 60 to 80 years with a testosterone level lower than 13.7 nmol/L, were randomized to receive 80 mg of testosterone undecenoate or matching placebo twice daily for 6 months.

Primary endpoints were functional mobility, measured with the Stanford Health Assessment Questionnaire, timed get-up-and-go test, isometric handgrip strength, and isometric leg extensor strength; cognitive function on 8 different cognitive tests; bone mineral density (BMD) of the hip and lumbar spine on dual-energy x-ray absorptiometry scanning; body composition assessed with total body dual-energy x-ray absorptiometry and abdominal ultrasonographic examination of fat mass; metabolic risk factors including fasting plasma lipids, glucose, and insulin levels; and quality of life on the 36-Item Short-Form Health Survey and the Questions on Life Satisfaction Modules.

Safety was monitored with serum prostate-specific antigen level; ultrasonographic prostate volume; International Prostate Symptom score; and serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, hemoglobin, and hematocrit.

Among 207 men who completed the study, lean body mass increased and fat mass decreased in the testosterone vs the placebo group. However, these improvements were not reflected in increased functional mobility or muscle strength, nor were there any changes in cognitive function and BMD.

Although insulin sensitivity improved, high-density lipoprotein (HDL) cholesterol levels decreased in the testosterone group. At the end of the study, metabolic syndrome was present in 47.8% in the testosterone vs 35.5% in the placebo group (P = .07). Most quality-of-life measures were similar in both groups, except for 1 hormone-related quality-of-life measure that improved in the testosterone group. There were no apparent adverse effects on prostate safety associated with testosterone.

"Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects," the study authors write.

Limitations of the study include inability to measure a post dose testosterone level; increase in testosterone in the placebo group attributed to regression to the mean; lack of availability of patches and gels, which provide more steady testosterone levels, in the Netherlands when this study was designed; and some missing data.

"This study is, as far as we know, the largest study of testosterone supplementation with the most end points and a randomized, double-blind design," the authors conclude. "The findings in this study do not support a net benefit on several indicators of health and functional and cognitive performance with 6 months of modest testosterone supplementation in healthy men with circulating testosterone levels in the lower range."

The Netherlands Organization for Health Research and Development supported this study. Organon NV (Oss, the Netherlands) provided the study medication. Three of the study authors have obtained funding. The remaining study authors have disclosed no relevant financial relationships.

JAMA. 2008;299:39-52.
Clinical Context

Testosterone levels gradually decrease among most men as they grow older, and this decrease has been associated with distinct clinical events. Reduced testosterone levels are linked with lower muscle mass and muscle strength, and lower testosterone values have also been associated with an increased risk of falling. In addition, lower testosterone levels may reduce bone mass and accelerate cognitive decline. Finally, reduced testosterone levels are associated with an increase in fat mass, particularly in the abdomen.

Despite these negative outcomes associated with lower serum levels of testosterone, the efficacy of exogenous testosterone therapy to improve these issues is not clear. The current study examines multiple outcomes of testosterone supplementation among older men.
Study Highlights

* Study subjects were men between the ages of 60 and 80 years and lived in the Netherlands. All participants had serum testosterone levels of less than the 50th percentile for their collective age (cutoff level < 13.7 nmol/L). Patients with a history of significant or uncontrolled chronic illness or prostate hyperplasia were excluded from study participation.

* Participants were randomized to receive 2 capsules of testosterone undecenoate 40 mg twice daily or matching placebo. Treatment period was 6 months.

* The main study outcomes were functional mobility, cognitive function, BMD of the hip and lumbar spine, body composition, metabolic risk factors, quality of life, and the safety of study treatment. Functional mobility was measured with subjective tools to assess daily function as well as objective strength measures. BMD and body composition were evaluated with dual-energy x-ray absorptiometry, and ultrasonographic examination was used in addition to assess fat mass. Safety focused on the well-being of multiple organs and included a rectal ultrasonographic examination to assess prostate volume.

* 237 men underwent randomization. The mean age was 67 years, and the mean concentration of serum testosterone at baseline was 10.7 nmol/L.

* 16 and 14 subjects withdrew from the testosterone and placebo groups, respectively, during the trial. Adherence to study therapy among other subjects was very good.

* Serum levels of total testosterone at 6 months were unchanged from baseline in the testosterone group but increased slightly in the placebo group. Sex hormone-binding globulin levels fell during treatment in the testosterone group only.

* Functional mobility and muscle strength were similar at 6 months in the testosterone and placebo groups, as were cognitive function and BMD.

* Total body fat mass decreased by 1 kg in the testosterone vs no change in the placebo group (P < .001). Total lean body mass was superior in the testosterone vs the placebo group.

* Both total and HDL cholesterol levels decreased with treatment in the testosterone group, although triglyceride and low-density lipoprotein cholesterol levels were not affected by study treatment.

* Testosterone therapy seemed to be protective against insulin resistance vs placebo, although the prevalence of the metabolic syndrome increased by a factor of 1.7 in the testosterone vs placebo group. This increase was mostly because of decreased HDL cholesterol levels associated with testosterone therapy and was nearly statistically significant.

* Quality-of-life scores were generally similar between the placebo and testosterone groups.

* Prostate volume, serum prostate-specific antigen levels, and lower urinary tract symptoms were similar between the testosterone and placebo groups.

* Testosterone increased hemoglobin levels and was also associated with higher serum creatinine values. Measures of liver function were similar between the testosterone and placebo groups.

* More than one half of participants reported adverse events. The frequency and type of adverse events were similar between the study groups.





Let wel aged 60 to 80 years with a testosterone level lower than 13.7 nmol/L Volgens mij ben ik die in de 30+ hoek nog niet tegengekomen

[philosopher]

Stond laatst ook al iets over in de krant. Tegen het verouderings proces, men werd er vitaler, gezonder en geestelijk gingen ze er op vooruit

[robintjuh]

ja had het ook al gelezen, leuk artikel 3XL!