Claire Gilbert ’26
Gender-affirming hormone therapy is an increasingly popular treatment. Its purpose is to administer sex hormones that induce physical and chemical changes consistent with a patient’s gender identity. This treatment addresses the significant gender dysphoria felt by transgender individuals and can help them physically present their desired gender. However, due to the lack of research on the long-term effects of different dosages of hormones, there is no definitive protocol for gender-affirming hormone therapy, and it has remained unclear how dosage may influence treatment.
A study in Japan performed by the Gender Center of Okayama University Hospital was published in April 2024, filling in the gaps in knowledge surrounding how dosage may influence the desired effects of gender-affirming hormone therapy. Specifically, the study investigated the long-term physical effects–both desired effects of the treatment and possible side effects–for transgender men. As found by the study, there were no long-term differences in physical or chemical changes between participants who received low or high doses of testosterone, nor were there any overall side effects. In other words, gender-affirming hormone therapy proved effective in producing the desired physical and chemical changes associated with masculinization, even at low doses.
The study utilized a retrospective analysis of 291 transgender men who had initiated their gender-affirming hormone therapy between the years of 2000 and 2021. The participants varied in their backgrounds–their ages and histories of health problems–but also in the level of dosage of testosterone they had received. Participants were therefore split into a “low dose” group (LD) if they received 62.5 mg or less of testosterone per week in their first year of gender-affirming hormone therapy, or into a “high dose” group (HD) if they received more than that amount. While most participants fell into the low-dose group (64.6%), some participants had sought higher dosages with the intention of receiving a stronger and faster masculinization.
To compare the efficacy of different doses of testosterone on promoting physical changes, measurements were taken of participants’ body mass index (BMI), lean body mass (LBM), and grip strength. BMI was used as a metric of overall growth, while LBM was a measure of the difference between total weight and body weight from fat, to determine the change of muscle mass specifically. Because many transgender patients seek the stereotyped “masculine” body shape, LBM is an important metric for patient satisfaction with their gender-affirming hormone therapy. Similarly, body fat percentage was measured to determine the opposite of LBM: how hormone therapy might change the distribution of fat in the body. Grip strength was also measured to determine whether the growth in muscle mass was correlated with an increase in muscle strength.
Figure 1: Changes in Body Mass Index, Body Fat Percentage, Lean Body Mass, and Mean Grip Strength across High Dosage and Low Dosage Groups
As found by the study, long-term low doses of testosterone were sufficient to induce masculine physical changes, but for faster results, higher doses of testosterone could be used. This change was most evident in LBM, which was higher in the high dosage group for the first 1-2 years, but which had no significant difference between the groups after that period. In other words, a higher dosage of testosterone could induce an earlier growth in muscle mass, but not significant differences in muscle mass over time. Across the other measurements, there was an increase in grip strength primarily within the first year of treatment, whereas BMI increased steadily over 10 years, with no differences in either measurement across dosage groups.
In addition to measuring physical changes, the study also noted chemical changes within the participants as a result of gender-affirming hormone therapy. The study measured hemoglobin (the protein that carries oxygen in red blood cells) and hematocrit (the percentage of volume of red blood cells), to understand the effects of hormone therapy on the body’s ability to transport oxygen through blood. Additionally, the study measured uric acid levels, because testosterone administration can sometimes lead to increased reabsorption of uric acid, and creatinine, which is an important marker of kidney function that also often changes during hormone therapy. The study also measured total testosterone levels as correlated to lower or higher dosages.
The chemical results found by the study showed that there were no levels of hemoglobin, hematocrit, uric acid, or creatinine beyond the normal range, although all four levels did increase within the first 12 months of treatment. Moreover, as anticipated, receiving a higher dosage of testosterone did correlate to higher testosterone levels in the body, but surprisingly, this difference was only observed within the first four years of treatment. In the long-term, there was no difference in testosterone levels between the low and high dosage groups. Key takeaways from these lab results are that there were no signs of long-term or dose-dependent side effects shown in abnormal lab results, and receiving higher doses of testosterone is only beneficial insofar as noticing results faster. Moreover, contrary to what was anticipated, the long-term effects are the same regardless of the dosage.
Overall, the study showed that long-term gender-affirming hormone therapy is both non-dangerous and beneficial in yielding the desired physical and chemical changes in transgender patients. However, there were significant limitations to this study, notably in the number of confounding variables due to the observational nature of the study. Because this was a retrospective analysis, rather than a controlled study, participants varied in factors which could influence the efficacy of treatment. These include age, history of surgical procedures (specifically hysterectomy and oophorectomy), adherence to the prescribed dosage, and even the route of testosterone administration. While the results are effective in demonstrating large-scale observations regarding overall safety and efficacy of hormone treatments, future controlled studies would be key to forming clear causal relationships between specific variables.
Claire Gilbert is a staff writer at The Princeton Medical Review. She can be reached at cg6209@princeton.edu.
References
1Tominaga Y, Kobayashi T, Matsumoto Y, et al. Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes. Andrology. 2024; 1-11. https://doi.org/10.1111/andr.13640
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