That is according to a new study led by researchers from Brigham and Women’s Hospital, Harvard Medical School in Boston. They asked the question: Can testosterone replacement therapy (TRT) correct anemia or prevent the development of anemia in middle-aged and older men with hypogonadism?
Their randomized clinical trial of 5,204 men with hypogonadism found that a greater proportion of testosterone-treated men corrected their anemia than placebo-treated men. In men without anemia at baseline, TRT also was associated with a lower incidence of anemia than placebo.
The study in the Journal of the American Medical Association Network Open pointed out that testosterone deficiency causes mild anemia. That led to the effort to assess the effectiveness of TRT in correcting anemia in men with hypogonadism and anemia, as well as reducing the risk of developing anemia in those without anemia.
The randomized, placebo-controlled trial included men with hypogonadism at 316 U.S. sites, with participants enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism.
To be eligible, participants had to be aged 45 to 80 years, with two testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March 2023 and August 2023.
The researchers randomized participants with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration.
The focus was on the proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. The incidence of anemia among men who were not anemic was a second endpoint.
Of the 5,204 men included, 815 had anemia (mean [SD] age, 64.8 [7.7] years; 247 were black [30.3%], 544 white [66.7%], 24 other [2.9%]); and 4,379 were without anemia (mean [SD] age, 63.0 [7.9] years; 629 were black [14.4%], 3603 white [82.3%], 147 other [3.4%]).
“Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs. 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs. 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs. 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs. 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs. 38 of 97 [39.2%]) (P = .002),” according to the authors. “Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level.”
Background information in the articles noted that anemia is prevalent in middle-aged and older adults and is associated with impaired quality of life, fatigue, mobility limitation, falls, and increased risk of mortality. Yet there is currently no approved therapy for unexplained anemia that occurs during aging.
“Testosterone deficiency causes mild normocytic anemia, and nearly 15% of older men with hypogonadism experience anemia,” the authors advised. “Testosterone treatment increases hemoglobin. Secondary analyses of a substudy of the Testosterone Trials (129 participants) reported that testosterone replacement therapy (TRT) increases hemoglobin in older men with hypogonadism and was associated with correction of anemia. However, a large, randomized efficacy trial of TRT in men with hypogonadism and anemia, and with anemia as its primary outcome, has not been conducted. Furthermore, it is unknown whether TRT can prevent the development of anemia in men with hypogonadism,” they added.
The study team wrote that “the magnitude of increase in hemoglobin in testosterone-treated men with anemia was not dissimilar from that reported with other erythropoiesis-stimulating agents and inhibitors of hypoxia-inducible factor prolyl hydroxylase that are approved for the treatment of anemia.” The team further states that TRT “was also associated with a greater proportion of men improving their hemoglobin by more than 1 g/dL, a level that has been used to evaluate meaningful treatment response in patients with anemia.”
The researchers posited that testosterone likely increases hemoglobin and red cell number by multiple mechanisms, including stimulating erythropoietin transcription, increasing iron availability for erythropoiesis by suppressing hepcidin transcription, increasing the numbers of common myeloid progenitors and improving red cell survival. “Testosterone corrects anemia of inflammation by improving iron availability and by promoting maturation of erythroid precursors,” they concluded.
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