Effect of testosterone formulations on hematocrit in transgender individuals: A systematic review

Approximately, 11% of trans men experience erythrocytosis diagnosis due to testosterone administration during the first year of the gender-affirming hormone treatment (GAHT).

To identify and compare the effect of different testosterone formulations on hematocrit (Hct) and diagnose erythrocytosis in trans men.

This systematic review was based on PRISMA guidelines. We performed an electronic search of PubMed, Embase, and Web of Science in January 2024. The Newcastle-Ottawa scale was used to evaluate the quality of evidence in the observational studies.

Of the 152 records retrieved, 18 met the eligibility criteria. Studies observed an increase of up to 5% in Hct in trans men using injectable testosterone undecanoate (TU), and up to 6.9% in trans men using intermediate injectable testosterone esters (TE). Trans men using TE experience a larger increase in serum Hct levels compared to those receiving TU. Erythrocytosis prevalence varies according to the cutoff used (50%, 52%, and 54%). Erythrocytosis was also associated with tobacco use, age at initiation of hormone therapy, body mass index (BMI), and pulmonary conditions. Studies that evaluated the effect of testosterone formulation on erythrocytosis diagnosis present conflicting result. Trans men have a hazard ratio of 7.4 (95% CI: 4.1, 13.4) of developing erythrocytosis compared to cisgender men, using a 52% hematocrit cutoff.

All testosterone formulations result in an increase in Hct, irrespective of dose, formulation, and administration method. Smoking, higher age at initiation of the testosterone therapy, higher BMI, and a predisposing medical history are associated with this increase in Hct. The difference in effect of TE and TU on Hct is conflicting, although it is important to point out that these data come from observational studies, retrospective, and with a small-sample size.