Written by Keen Meds · Reviewed by Licensed Clinical Providers · March 1, 2026
Key Insight: The TRAVERSE anemia sub-study (JAMA 2023) found testosterone corrected unexplained anemia in 54.4% of treated men vs. 26.3% of placebo-treated men — more than double the spontaneous correction rate — demonstrating TRT as an effective treatment for anemia of aging in hypogonadal men.
Fatigue is one of the most common symptoms that leads men to investigate testosterone levels. What many do not know is that fatigue and low energy can have two separate contributors that often coexist: low testosterone itself, and anemia, which is a reduction in the red blood cells that carry oxygen through the body. In hypogonadal men, both problems frequently exist at the same time, for a related biological reason.
The TRAVERSE anemia sub-study, published in JAMA in 2023, provided the most rigorous clinical evidence to date that testosterone therapy corrects unexplained anemia in hypogonadal men at rates substantially higher than placebo. Understanding this finding, its implications, and its counterpart, the risk of hematocrit rising too high, helps men and their clinical providers approach testosterone therapy with a complete picture of what to expect.
About the Study: Design and Why It Was Done
The TRAVERSE anemia sub-study was led by Karol Pencina and colleagues and published in JAMA in 2023, concurrent with the main TRAVERSE cardiovascular trial.
To understand why this investigation was warranted, a brief look at testosterone's role in blood production is necessary. Testosterone stimulates erythropoiesis, the process by which the body produces red blood cells, through several mechanisms. The most established pathway is direct stimulation of erythropoietin production in the kidneys. Erythropoietin is the signaling hormone that tells the bone marrow to produce more red blood cells. Testosterone also has direct effects on bone marrow stem cells and suppresses hepcidin, a hormone that otherwise restricts iron availability for red blood cell production.
This biology explains why testosterone levels and red blood cell production are linked. Men with very high testosterone, including those who use anabolic steroids, can develop polycythemia, an excess of red blood cells. Men with very low testosterone may develop anemia, particularly the type often labeled "anemia of aging," in which no specific nutritional, bleeding, or disease cause is identified.
The sub-study enrolled men from the TRAVERSE population who had documented unexplained anemia at baseline, defined as hemoglobin below 12.5 g/dL in the absence of an identified cause such as iron deficiency, vitamin B12 deficiency, bleeding, or a known chronic disease that causes anemia. These were men whose anemia had no clear explanation under standard workup.
What the Study Found
The primary finding: 54.4% of men in the testosterone-treated group had their anemia corrected by the end of follow-up, compared to 26.3% of men in the placebo group. The difference was highly statistically significant.
This means testosterone therapy more than doubled the rate of anemia correction compared to placebo. The spontaneous correction rate in the placebo group, at 26.3%, likely reflects a combination of natural fluctuation, improved nutrition, or non-study treatments. The additional correction seen in the testosterone group, above that background rate, is attributable to the direct effect of testosterone on erythropoiesis.
The effect was observed in men with both mild and moderate anemia at baseline. Men with more severe anemia showed similar directional benefit, though absolute hemoglobin gains were tracked across the distribution.
Importantly, the study also tracked the opposite problem: hematocrit rising too high. Hematocrit is the proportion of blood volume composed of red blood cells, and testosterone therapy can elevate it in a meaningful minority of men. The study found that polycythemia, defined as hematocrit above 54%, occurred more frequently in the testosterone-treated group. This finding reinforced what clinical practice already required: routine hematocrit monitoring during testosterone therapy.
What the Critics Said: Limitations and Context
The anemia sub-study has been well-received, as it addresses a clinically significant gap in the literature: the identification and treatment of hormonally driven anemia in older men.
One important contextual note is the definition of "unexplained anemia" used in the study. Standard clinical workup for anemia includes checking iron stores, B12, folate, renal function, and thyroid function, among other tests. Men who entered this sub-study had no identified cause on that workup. In real-world practice, a proportion of men with previously labeled "anemia of aging" may in fact have nutritional or disease causes that a more thorough workup would uncover. The sub-study's findings apply most directly to men whose anemia genuinely has no identifiable cause after a complete evaluation.
The spontaneous correction rate of 26.3% in the placebo group also reminds clinicians that anemia in older men is not always stable or permanently unexplained. Some cases resolve on their own. This background rate is accounted for statistically in the comparison, but it is worth noting when counseling individual patients.
The polycythemia finding is not a limitation of the study but rather an important clinical monitoring signal. The study confirmed what clinicians already knew to monitor: as testosterone raises red blood cell production, it can overshoot in some men, and hematocrit must be checked at defined intervals.
What This Means for You Today
For hypogonadal men who have been told they have unexplained anemia or anemia of aging, the TRAVERSE sub-study findings are directly relevant. Testosterone deficiency may be an unrecognized contributing cause, and treatment of the testosterone deficiency may resolve the anemia alongside the other symptoms of low testosterone.
This dual-benefit profile, addressing both testosterone deficiency symptoms and anemia simultaneously, is clinically meaningful. Anemia causes fatigue, reduced physical capacity, cognitive slowing, and reduced quality of life on its own. Correcting it through testosterone treatment rather than through separate interventions is an efficiency that supports treatment in this population.
The monitoring requirement is equally important to understand. Every man on testosterone therapy should have hematocrit checked at approximately three months after starting treatment or after any dose adjustment, and at least annually thereafter. The threshold for clinical action is hematocrit at or above 54%. When hematocrit reaches this level, standard clinical options include dose reduction, temporary treatment pause, or, in some cases, therapeutic phlebotomy, which is simply donating blood to reduce red blood cell volume.
Men who are high-risk for hematocrit elevation include those with baseline hematocrit in the high-normal range (already above 48%), prior history of clotting events, sleep apnea (which independently raises hematocrit), or those living at high altitude, where the body naturally increases red blood cell production in response to lower oxygen availability.
Frequently Asked Questions
Can testosterone therapy treat anemia?
The TRAVERSE anemia sub-study found that testosterone therapy corrected unexplained anemia in 54.4% of treated men compared to 26.3% of placebo-treated men. This suggests TRT can be an effective treatment for anemia of aging in hypogonadal men whose anemia has no other identified cause. However, anemia should always be fully evaluated first to identify any treatable underlying cause before attributing it to testosterone deficiency.
What is polycythemia and why does it matter with testosterone therapy?
Polycythemia is an elevation of red blood cell mass, reflected as an elevated hematocrit. In the context of testosterone therapy, polycythemia typically means hematocrit rising above 54%. At elevated levels, blood viscosity increases, which can raise the risk of clotting. This is why hematocrit monitoring is a mandatory component of care for men on testosterone therapy. The condition is manageable through dose adjustment or, if needed, therapeutic phlebotomy.
How often should hematocrit be checked on testosterone therapy?
Standard clinical practice calls for hematocrit measurement at approximately three months after starting testosterone or after any dose change, and then at least annually once a stable level is established. If hematocrit rises significantly between scheduled checks, more frequent monitoring is appropriate. Men with risk factors for polycythemia may be monitored more frequently.
If I have anemia, should I start testosterone therapy to treat it?
Testosterone therapy is not a first-line treatment for anemia in the general population. For men who have both confirmed hypogonadism and unexplained anemia, treating the testosterone deficiency may address both problems. But the appropriate starting point is a full evaluation of the anemia's cause, confirmation of low testosterone, and an individualized clinical discussion. Testosterone therapy requires a valid clinical indication beyond anemia alone in most cases.
What the Research Means for Your Treatment Options
The connection between low testosterone and anemia of aging is mechanistically well-established and now supported by rigorous randomized clinical trial evidence. For hypogonadal men with unexplained anemia, addressing testosterone deficiency may provide a dual clinical benefit. Appropriate monitoring for hematocrit ensures that the same mechanism driving benefit is kept within safe parameters throughout treatment.
Keen Meds connects you with licensed clinical providers for a telehealth evaluation and lab review. If your testosterone is clinically low, you may qualify for Testosterone Spray Rx, a needle-free transdermal testosterone program.
