Serum Hormone Concentrations in Transgender Individuals Receiving GAHT



To examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals.

Methods: This retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.

Results: Overall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones.

Conclusion: In transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was a positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.


Many transgender and gender nonbinary (TGGNB) people receive gender-affirming hormone therapy (GAHT) to align their gender identity with their secondary sexual characteristics.1 Other way in which TGGNB people affirm their gender identity includes social transitioning, voice therapy, and gender affirmation surgery.2 The goal of GAHT is to closely mirror the sex steroid concentrations found within the reference range of the affirmed gender.3 Over a period of 2 to 3 years, GAHT typically results in physical changes expected for the affirmed gender. In transfeminine individuals, GAHT leads to an increased volume of breast tissue, redistribution of subcutaneous fat, and changes in the skin and hair. In transmasculine individuals, GAHT causes deepening of the voice, an increase in muscle mass, redistribution of subcutaneous fat, and increased facial and body hair.4-6

Although GAHT is considered safe under medical supervision,7-11 evidence indicates that TGGNB people may experience potential adverse effects, such as polycythemia secondary to testosterone administration and venous thromboembolism (VTE) owing to estrogen use.9,12 The Endocrine Society’s guidelines suggest monitoring and adjusting hormone medications to maintain the hormone levels within the desired sex-specific physiologic range of the affirmed gender to minimize these risks.1,2 However, published data on hormone dosing and corresponding blood concentrations are limited in the literature.7,13,14 It is important for clinicians to have a better understanding of the impact of the the dose of hormone preparation, route of administration, and frequency of dosing on blood hormone levels to ensure the safety of GAHT regimens.11,15

The purpose of this study was to examine the effect of various GAHT regimens on blood hormone concentrations in transfeminine and transmasculine individuals receiving care at a single center. We included all subjects who were receiving GAHT over a 15-year period and collected data on the details of their hormone regimen and hormone concentrations.

*All routes of testosterone are equally effective in raising serum hormone concentrations to the male reference range; however, injectable testosterone appeared to be more likely to raise the median testosterone concentrations to the range of 400 to 700 ng/ dL, as recommended by the Endocrine Society. Intramuscular testosterone was the most popular route among transgender men in our clinic. Testosterone doses of 100 to 200 mg every 1 or 2 weeks resulted in target concentrations. Transdermal preparations resulted in lower serum testosterone concentrations, which were not in the recommended range.

In conclusion, several routes and formulations of sex steroid hormones used in the United States produced target hormone concentrations in our patient population. In transgender men, all the routes and formulations of testosterone appeared to be equally effective in achieving target hormone concentrations. In the transgender women, there was a dose-dependent increase in the serum estradiol concentration with increasing oral doses of estradiol, with a dose of 5 mg daily appearing to be effective in achieving adequate estradiol concentrations. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration of estradiol. The transgender women undergoing bilateral orchiectomy had higher serum estradiol concentrations, which confirms the expectation that the estradiol dose can be lowered after gonadectomy.


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Table 2 Sex Steroid Hormone Concentrations in Transgender Men and Women According to Demographic Characteristics
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Table 3 Serum Concentrations of Total Testosterone in Transgender Men by Route of Administration and Dose
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Table 4 Serum Concentrations of Total Estradiol in Transgender Women by Route of Administration and DoseScreenshot (3268).png


Fig. 2. The total daily dose of oral estradiol and the corresponding serum estradiol concentration in transgender women taking gender-affirming hormone therapy. The serum estradiol concentrations demonstrated a dose-dependent increase with an increasing total daily dose of oral estradiol (P < .001, Kruskal-Wallis). A total daily dose of between 4 and 5 mg resulted in a median estradiol concentration of 93.5 pg/mL (interquartile range: 58.6-146.8), which is near the minimum recommended therapeutic range for transgender women
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