Use of testosterone does not lead to abnormal hematocrit levels

Receipt of testosterone as a part of gender-affirming hormone therapy (GAHT) did not lead to an increased prevalence of erythrocytosis or abnormal hematocrit levels, according to recent findings published in The Journal of Clinical Endocrinology & Metabolism.¹

Data showed increased levels of hematocrit with higher levels of testosterone (P < .001), which met statistical significance, though the absolute levels of hematocrit remained within the normal range.

The findings suggest that testosterone can safely be taken as a masculinizing treatment.

“A major concern of patients, providers, and parents is the safety of hormone therapy for transgender and gender-diverse people. The findings from this study represent very important reassurance regarding the safety of testosterone as masculinizing treatment. Providers should feel more comfortable prescribing testosterone when it is indicated. Patients and the families of patients should feel reassured regarding at least this one source of anxiety about treatment,” said senior author Joshua Safer, MD, FACP, FACE, in a news release on the findings.² Safer is the executive director of the Mount Sinai Center for transgender medicine and surgery and a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York, New York.

In total, the study assessed hematocrit levels among 6670 patients who were prescribed testosterone and had recent hematocrit and testosterone laboratory values available for analysis. Outcomes of interest included the prevalence of erythrocytosis and the mean hematocrit levels at predetermined testosterone thresholds and with varying administration methods.

Among all patients, the mean hematocrit level ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Significant variation in hematocrit levels were observed among patients in different testosterone thresholds.

Data showed increased levels of hematocrit with higher levels of testosterone (P < .001), which met statistical significance, though the absolute levels of hematocrit remained within the normal range. Overall, 560 (8.4%) of patients had a hematocrit level greater than 50%, 182 (2.7%) had a level greater than 52%, and 60 (0.9%) had a level greater than 54%, which is the level at which treatment for erythrocytosis is recommended, according to the news release.²

“Our study found that the numbers of patients on testosterone therapy with abnormal red blood cell elevations were lower than previously reported in smaller studies. It’s noteworthy that in the largest North American cohort reported to date, less than 1% of transmasculine individuals had a hematocrit level where medical interventions might be required. These results should help providers feel more comfortable prescribing testosterone as part of GAHT,” said lead author Nithya Krishnamurthy, a second-year medical student at Icahn Mount Sinai, in the news release.²

The investigators also found a statistically significant association between the magnitude of change in hematocrit level and route of administration (P < .001). Patients on intramuscular testosterone had a mean hematocrit level of 44.96%, compared with 43.41% among those on transdermal testosterone, though the difference is unlikely to be clinically meaningful, according to the authors.

Krishnamurthy concluded in the news release, “This work suggests a need to assess the influence of other factors that can lead to secondary erythrocytosis; such as being overweight, smoking tobacco, or using alcohol.”²

References

1. Krishnamurthy N, Slack DJ, Kyweluk M, et al. Erythrocytosis is rate with exogenous testosterone in gender-affirming hormone therapy. Published online and accessed November 27, 2023. J Clin Endocrinol Metab. doi:10.1210/clinem/dgad651

2. Mount Sinai researchers find testosterone hormone therapy for transmasculine individuals is safer than previously thought. News release. Mount Sinai Health System. November 20, 2023. Accessed November 27, 2023. https://www.newswise.com/articles/mount-sinai-researchers-find-testosterone-hormone-therapy-for-transmasculine-individuals-is-safer-than-previously-thought