February 22, 2017
3 min read

Testosterone treatment improves bone density, strength in older men

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One year of testosterone treatment significantly increased volumetric bone mineral density and estimated bone strength in men aged 65 years and older, according to data published in JAMA Internal Medicine.

“As men age, they experience decreases in serum testosterone concentration,” Peter J. Snyder, MD, from the Perelman School of Medicine at the University of Pennsylvania. “They also experience decreases in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and estimated strength and an increase in fractures.”

“Prior studies of the effect of testosterone treatment on bone in older men, however, have not been conclusive,” they added.

Snyder and colleagues conducted a multicenter, placebo-controlled, double-blind trial to determine if testosterone treatment increases vBMD and bone strength in older men with low testosterone. They enrolled 211 men aged 65 years or older (mean age, 72.3 years; 86% white; mean BMI, 31.2 kg/m2) who participated in the Testosterone Trials between December 2011 and June 2014 and had two testosterone levels averaging less than 275 ng/L.

The researchers allocated participants by minimization to receive testosterone or placebo gel for 1 year, adjusting testosterone gel to maintain levels that correlate to the normal range for young men. They used quantitative CT to determine spine and hip vBMD at baseline and 12 months and dual energy X-ray absorptiometry was used to determine areal BMD at baseline and 12 months. In addition, they used a finite element analysis of quantitative CT data to estimate bone strength.

Compared with participants in the placebo group, those in the testosterone group showed significantly greater increases in mean spine trabecular vBMD (7.5% [95% CI, 4.8-10.3] vs. 0.8% [95% CI, –1.9-3.4]; treatment effect, 6.8% [95% CI, 4.8-8.7]; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD. These participants also displayed significantly greater increases in mean estimated strength of spine trabecular bone (10.8% [95% CI, 7.4-14.3] vs. 2.4%; [95% CI, –1 to 5.7]; treatment effect, 8.5% [95% CI, 6.-10.9]; P < .001), spine peripheral bone, and hip trabecular and peripheral bone. The researchers noted that the increases in estimated strength were larger in trabecular than peripheral bone and larger in the spine than hip. Spine areal BMD increased as a result of testosterone treatment, but in a lesser magnitude than vBMD.

“The clinical significance of the effect of testosterone treatment on vBMD and estimated bone strength in these men will depend on whether testosterone treatment also reduces fracture risk,” Snyder and colleagues concluded. “Some evidence suggests that it might. Bone strength, as estimated by FEA of QCT data, does correlate well with physical strength of human vertebrae and is associated with prevalent bone fractures and incident spine and hip fractures. Only a larger and longer trial, however, will determine whether testosterone treatment does reduce fracture risk in older men with low testosterone levels.”

This study is part of the Testosterone Trials, an effort by the NIH to study testosterone treatment effects in 790 men aged 65 and older.

“A number of older men have testosterone levels below those found in healthy younger men,” Richard J. Hodes, MD, director of the National Institute on Aging, said in a press release. “In most cases, these low levels are not due to diseases known to affect testosterone levels. Many of these men also have problems that could be related to low testosterone, including impaired cognition, anemia, cardiovascular disease, diminished sexual function, decreased mobility and fatigue. The T Trials were designed to determine if testosterone treatment might help alleviate these symptoms and conditions while monitoring for adverse effects.”

The trials revealed that 1 year of testosterone therapy in older men improved hemoglobin levels in addition to bone strength, may increase cardiovascular risk and had no effect on cognition, according to the NIH.

“The results on diverse outcomes indicate the potential trade-offs between benefits and risks of testosterone treatment in older men,” Evan Hadley, MD, director of NIA’s Division of Geriatrics and Clinical Gerontology, said in the release. “However, clarifying the effects of testosterone on many major clinical outcomes such as cardiovascular events, fractures, and disability will require longer, larger scale trials. The results also illustrate that decisions about testosterone treatment need to be individualized, taking into account each patient’s balance of risks for the various conditions that testosterone treatment could affect.” – by Alaina Tedesco

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Disclosure: Snyder reports receiving grants from the National Institute on Aging, National Institutes of Health and grants and nonfinancial support from AbbVie during the conduct of the study, as well as personal fees from Watson Laboratories, outside the submitted work. Please see full study for all other authors’ relevant financial disclosures. The Testosterone Trials were primarily funded by the National Institute on Aging.