Testosterone replacement therapy (TRT) may improve anemia and bone density among older hypogonadal men, new studies suggest.
Cindy N. Roy, PhD, of Johns Hopkins University in Baltimore, and colleagues conducted a double-blind study of 788 men aged 65 years and older who had average testosterone levels less than 275 ng/dL. Of these, 126 had anemia (hemoglobin levels of 12.7 g/dL or less), 62 of whom had no known cause. Investigators randomly assigned men to receive testosterone gel or placebo for 12 months. The main outcome measure was the proportion of men with unexplained anemia whose hemoglobin levels increased by at least 1.0 g/dL in response to testosterone compared with placebo.
Among men with unexplained anemia, a significantly greater percentage of those on TRT compared with placebo had a 1.0 g/dL or greater increase in hemoglobin at month 12 (54% vs 15%) and correction of anemia at month 12 (58.3% vs 22.2%), the investigators reported online ahead of print in JAMA Internal Medicine. In addition, TRT resulted in a significantly greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by at least 1.0 g/dL compared with placebo (52% vs 19%).
In adjusted analyses, TRT for 12 months among men with anemia of unknown cause was associated with significant 31.5-fold greater odds of 1.0 g/dL increase in hemoglobin and 17-fold greater odds of anemia correction compared with placebo. TRT for 12 months among men with anemia of known cause was associated with a significant 8.2-fold greater odds of a 1.0 g/dL or greater increase in hemoglobin level.
“Among older men with low testosterone, testosterone treatment significantly increased hemoglobin levels in those with unexplained anemia and those with anemia associated with known causes,” Dr Roy and her colleagues concluded. “These increases may be of clinical significance, as suggested by the magnitude of the increases and the correction of anemia in the majority of men. … These results also suggest that measurement of serum testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of hypogonadism.”
In a separate study published online ahead of print in JAMA Internal Medicine, researchers led by Peter J. Snyder, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, found that older men on TRT for 1 year experienced increased volumetric bone mineral density (vBMD) and estimated bone strength compare with men who received placebo. The beneficial effect was greater in trabecular than peripheral bone and in the spine compared with the hip.
The study included 211 men aged 65 years and older (mean 72.3 years, 86% white) with 2 testosterone measurements averaging less than 275 ng/L. The investigators randomly assigned patients to receive testosterone gel or placebo gel for 1 year. Compared with placebo, TRT was associated with significantly greater increases in mean spine trabecular vBMD (7.5% vs 0.8%), spine peripheral vBMD, and hip trabecular and peripheral vBMD. Testosterone treatment significantly increased estimated strength of spine trabecular bone compared with placebo (10.8% vs 2.4%).
Study strengths included unequivocally low testosterone levels of study participants, the double-blind study design, and excellent participant retention, according to the researchers. In a discussion of study limitations, they noted that because all patients had low serum testosterone levels, the results apply only to this population. Also, most men did not have osteoporosis by baseline T-scores, so “the results cannot be extrapolated to men who have osteoporosis but not low testosterone.”
Commenting on the study by Dr Roy and colleagues, Eric Orwoll, MD, of Oregon Health & Sciences University in Portland, said in an accompanying editorial, “These results provide very strong evidence that testosterone therapy in older men with low testosterone levels yields a positive skeletal effect.”
Dr Orwoll pointed out that the study was not designed to address whether TRT decreases fracture risk. “This is an essential question that has important clinical implications.”
1. Roy CN, Snyder PJ, Stephens-Shields AJ, et al. Association of testosterone levels with anemia in older men. A controlled trial. JAMA Intern Med 2017 published online ahead of print. doi:10.1001/jamainternmed.2016.9540
2. Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone. A controlled clinical trial. JAMA Intern Med 2017; published online ahead of print. doi:10.1001/jamainternmed.2016.9539
3. Orwoll E. Further elucidation of the potential benefits of testosterone therapy in older men. JAMA Intern Med 2017; published online ahead of print. doi:10.1001/jamainternmed.2016.9576