Blood thickening tied to gender-affirming testosterone is rare

People who take testosterone as gender-affirming care face a risk that the hormone will thicken their blood, leading to a side effect that requires bloodletting treatment. But now, the largest study of its kind in the U.S. suggests that this effect is actually far less common than previously thought.

In revealing that the side effect is rare, the study assuages one of the few medical concerns that come with gender-affirming testosterone, co-senior study author Dr. Daniel Slack, a second-year endocrinology fellow at Mount Sinai Hospital in New York, told Live Science.

The sex hormone testosterone is prescribed to treat cisgender men who don't produce enough of it and as part of masculinizing hormone therapy for transgender and gender-diverse people. This therapy drives the development of male secondary sex characteristics — for example, by deepening the voice, increasing body hair and redistributing fat — while suppressing female characteristics, such as menses (periods).

However, testosterone can also increase the concentration of red blood cells in the blood, causing a condition known as erythrocytosis, which thickens the blood and slows blood flow, potentially leading to life-threatening blood clots.

The new study included more than 6,600 transmasculine individuals receiving testosterone in the U.S. — the largest North American cohort reported to date — and revealed that less than 1% developed a concentration of red blood cells that would warrant medical intervention, such as bloodletting, and for hormone therapy to be stopped.

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The authors hope that the findings, published Monday (Nov. 27) in The Journal of Clinical Endocrinology and Metabolism, will reassure patients and help clinicians feel more comfortable prescribing testosterone.

"The one outstanding concern that folks do tend to have with testosterone is the risk of erythrocytosis," Slack said. "And we've shown that, even that risk — the one thing that people still worry about — is exceedingly low in users of masculinizing gender-affirming hormone therapy."

Testosterone is thought to increase the concentration of red blood cells in the blood by stimulating a red-blood-cell-producing hormone called erythropoietin. It may also increase the availability of another red blood cell ingredient: iron. Most clinicians are aware that erythrocytosis is a potential side effect of testosterone gender-affirming hormone therapy. But prior to the new study, it wasn't clear how common it was.

The study authors analyzed the levels of testosterone and concentration of red blood cells in the blood of 6,670 transmasculine individuals. The latter measure is referred to as "hematocrit," or the percentage by volume of a person's blood that's made up of red blood cells. All of the participants had been receiving testosterone as part of gender-affirming hormone therapy for at least three months before the study.

Higher levels of testosterone were associated with higher hematocrit levels. However, in most cases, the size of this change was "small" and "unlikely to be clinically meaningful," lead study author Nithya Krishnamurthy, a second-year medical student at the Icahn School of Medicine at Mount Sinai, told Live Science.

Normally, the safe hematocrit range for male adults is around 40% to 54%, with anything higher needing treatment. The participants who took testosterone via muscular injection had slightly higher average hematocrit levels than those who received it using a patch or gel — a difference of 44.96% compared with 43.41%. The difference possibly stems from the amount of testosterone the body is exposed to, they wrote in the paper, given that injectable, long-lasting testosterone results in higher, sustained levels of the hormone than gels applied daily. 

Overall, regardless of how testosterone was administered, only 8.4% of participants had hematocrit levels that exceeded 50%, and less than 1% had levels greater than 54%, the threshold for treatment. This amounted to 560 and 60 people out of 6,670, respectively.

Future research should assess the influence of other factors that can lead to secondary erythrocytosis, a scenario in which the condition develops as a result of other disorders, Krishnamurthy said. These other factors include being overweight, smoking tobacco or abusing alcohol, she said, so the team wants to understand how these factors might interact with testosterone therapy, especially over time.

In the meantime, they believe their current findings will help give patients and providers peace of mind.

"The low prevalence of this clinically meaningful change in hematocrit level should provide some reassurance for clinicians, patients and their families about initiating gender-affirming hormone therapy and help to facilitate discussions of informed consent between providers and their patients," Krishnamurthy said.

This article is for informational purposes only and is not meant to offer medical advice.

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