How Gender-Affirming Treatment Affects Erythrocytosis


The use of testosterone as gender-affirming hormone therapy (GAHT) among transgender men is associated with a lower risk for erythrocytosis (abnormal blood cell elevation) than was previously reported, results from a large study show.

Some differences are observed in hematocrit across a range of testosterone levels and between administration routes; however, the magnitude of change is relatively small and unlikely to have clinical implications, the authors report.


  • In this cross-sectional analysis, the authors evaluated testosterone and hematocrit laboratory values among 6670 transgender male patients prescribed testosterone through Plume, a national provider of GAHT.

  • Administration routes were either intramuscular, subcutaneous, or transdermal.

  • Patients had been on testosterone for at least 3 months at the time of analysis, June 2023.

  • Hematocrit and testosterone laboratory values represented the latest available for patients, who have blood samples collected every 3 months, targeting midcycle levels for all patients using the injectable forms of testosterone.

  • Total testosterone was measured with liquid chromatography-mass spectrometry, and hematocrit was calculated as part of a complete blood count.

  • Patients had an average age of 27 years (range 18-65 years).


  • Of the patients, 560 (8.4%) had hematocrit levels above 50%; 182 (2.7%) had levels above 52% and 60 (0.6%) had levels above 54%, which is the level associated with an increased risk for cardiovascular mortality observed in the Framingham Heart Study.

  • Hematocrit levels varied significantly based on testosterone level thresholds, with higher hematocrit levels observed among patients with higher testosterone levels (P < .001).

  • Overall, 41.2% of the cohort had testosterone values ≥ 600 ng/dL, with normal male testosterone values in the range of 300-1000 ng/dL.

  • Mean hematocrit ranged from 41.84% for testosterone levels < 50 ng/dL, representing a typically female testosterone range, to 45.68% for testosterone levels of 900-949 ng/dL.

  • The use of intramuscular testosterone was associated with a higher mean hematocrit compared with the use of transdermal testosterone (44.96% vs 43.41%; P < .001).

  • Mean hematocrit was highest for those in the 51-65 age group, at 45.44% vs 45.20% for those in the age–31-50–years group and 44.56% for those in the age–18-30–years group.

  • The route of administration (P < .001) and testosterone level (P < .001) were each significantly associated with hematocrit when controlling for each other.


The authors note that it’s important that in all the analyses, the differences in hematocrit across the range of testosterone levels and between administration routes were small. Even at cohort extremes, the mean hematocrit remained in “safe range.”

Overall, “providers should feel more comfortable prescribing testosterone when it is indicated,” said senior author Joshua Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery and professor of medicine at the Icahn School of Medicine at Mount Sinai, in a press statement.


The study was published November 20 in The Journal of Clinical Endocrinology and Metabolism.


Due to the cross-sectional nature of the study, changes in testosterone and hematocrit over time with ongoing use of exogenous testosterone could not be examined, and “it is possible that hematocrit levels would have regressed to the mean if observed over time,” the authors note.

In addition, comparing injectable roots of administration to transdermal administration is confounded by the expected variability in testosterone levels.


The authors had no disclosures to report.

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