, according to a new analysis published online in JAMA Network Open.
The analysis comes from a randomized, placebo-controlled trial that included 5,204 men with hypogonadism at 316 U.S. sites. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study. That study looked at whether TRT had an effect on major cardiovascular events and results were published earlier this year in the New England Journal of Medicine.
Hypogonadism increases with age
Hypogonadism includes specific symptoms in addition to a low testosterone level and has a lower prevalence (about 6%-12% vs. about 25% with low testosterone alone) in men 40-70 years old in the Massachusetts Male Aging Study (MMAS). But it is still common and increases with age, note authors of the current study, led by Karol M. Pencina, PhD, with the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital and Harvard Medical School, Boston.
Symptoms of hypogonadism include lower libido, erectile dysfunction, fatigue, reduced muscle mass, poor concentration, and disturbed sleep.
No approved treatment
Currently, there is no approved treatment for unexplained anemia during aging and nearly 15% of older men with hypogonadism experience anemia, the authors explain.
The proportion of participants whose anemia was corrected was significantly higher in the TRT group than the placebo group at 6 months (143 of 349 [41.0%] vs. 122 of 360 [27.5%]), 12 months (45.0% vs. 33.9%), 24 months (42.8% vs. 30.9%), 36 months (43.5% vs. 33.2%), and 48 months (44.6% vs. 39.2%); omnibus test P = .002.
A second aim in the study was to determine the effect of TRT on the development of anemia in participants who did not have anemia at enrollment.
In that group, a significantly smaller proportion of participants in the treatment group developed anemia, compared with the placebo group at 6 months (143 of 1,997 [7.2%] vs. 203 of 1,958 [10.4%]), 12 months (7.1% vs. 9.0%), 24 months (10.0% vs. 12.3%), 36 months (10.0% vs. 12.9%), and 48 months (9.0% vs 10.2%); omnibus test P = .02.
The men in the study had an average age of 64.8; 66.7% were White; 30.3% were Black; 2% were other.
Clinical implications
Shabbir M. H. Alibhai, MD, MSc, with the Institute of Health Policy, Management, and Evaluation, Institute of Medical Sciences, department of medicine, University of Toronto, writes in an invited commentary that this is one of the largest trials of TRT and was well-designed and executed. He points out that it had a long follow-up (mean duration on TRT was more than 20 months).
Given the results, he says, “TRT appears to be generally safe in middle-aged and older men with symptomatic hypogonadism, corrected mild anemia in 10%-15% of recipients, and prevented anemia in 2%-3%, with small improvements in energy but no effect on self-reported cognitive function.”
He said that without further details on long-term benefit, “I would not offer TRT primarily to treat asymptomatic normocytic anemia in men with low testosterone levels. It is reasonable to offer TRT to men with symptomatic hypogonadism regardless of hemoglobin level.”
He advises counseling patients that they could see small increases in hemoglobin levels with TRT, with a small boost in energy if they had anemia, but the effect on cognition, well-being, or function is unclear.
He further advised, “Hemoglobin levels should be monitored in men starting TRT (to detect the development of polycythemia), and prostate-specific antigen levels should be normal prior to start of treatment. Of course, a basic workup for causes of anemia, guided by history and basic parameters such as the mean corpuscular volume and blood film, should be performed in all men with anemia regardless of levels.”
The study was funded by a consortium of testosterone manufacturers led by AbbVie. Coauthors Dr. Artz, Dr. Chan, and Dr. Diegel report receiving consulting fees, grants, or employment from several pharmaceutical companies including AbbVie. Dr. Alibhai reports no relevant financial relationships.