Serum hormone concentrations in transgender people

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SERUM HORMONE CONCENTRATIONS IN TRANSGENDER INDIVIDUALS RECEIVING GENDER AFFIRMING HORMONE THERAPY: A LONGITUDINAL RETROSPECTIVE COHORT STUDY




Objective:
To examine the association of various gender affirmation hormone therapy (GAHT) regimens with blood hormone concentrations in transgender individuals.

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

Results: Overall 196 subjects (134 trans women, 62 trans men) with a total of 941 clinical visits were included in this study. Trans men receiving transdermal testosterone had a significantly lower median value of total serum testosterone when compared to those who were receiving injectable preparations (326.0 vs. 524.5 ng/dL respectively, p=0.018). Serum total estradiol concentrations of trans women were higher in those receiving intramuscular estrogen compared to those receiving oral and transdermal estrogen (366.0 vs. 102.0 vs. 70.8 pg/mL respectively, p<0.001). A dose-dependent response in hormone levels was observed for oral estradiol (p<0.001) and injectable testosterone (p=0.018), but not for intramuscular estradiol and not for transdermal formulations. Older age and history of gonadectomy in both trans men and women were associated with significantly higher concentrations of serum gender-affirmed hormone.

Conclusion: In trans men, all routes and formulations of testosterone appear to be equally effective in achieving concentrations in the male range. Intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol whereas transdermal estradiol resulted in the lowest concentration. The dose was directly related to hormone levels for oral estradiol and injectable testosterone.






Introduction

Many transgender and gender non-binary people (TGGNB) people receive gender-affirming hormone therapy (GAHT) to align their gender identity with their secondary sex characteristics [1]. Other ways that TGNB people affirm their gender identity include 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 2-3 years, GAHT typically results in physical changes expected for the affirmed gender. In transfeminine individuals, GAHT produces an increased volume of breast tissue, redistribution of subcutaneous fat, and changes in 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 TGNB people may have potential adverse effects, such as polycythemia secondary to testosterone administration, and venous thromboembolism due to estrogen use [9, 12]. The Endocrine Society guidelines suggest monitoring and adjusting hormone medications to maintain 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 dose of the 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 had data on the details of the hormone regimen and hormone concentrations.






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

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Figure 2 Total daily dose of oral estradiol and the corresponding serum estradiol concentration in trans women taking gender-affirming hormone therapy Serum estradiol concentrations demonstrated a dose-dependent increase with an increasing total daily dose of oral estradiol (p < 0.001, Kruskal-Wallis). A total daily dose of between 4 and 5 mg daily resulted in a median estradiol concentration of 93.5 pg/mL (IQR 58.6 – 146.8), which is near the minimum recommended therapeutic range for trans women.
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Table 2. Sex Steroid Hormone Concentrations in trans men and women according to demographic characteristics.
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Table 3 Serum concentrations of total testosterone in trans men by route of administration and dose*
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Table 4 Serum concentrations of total estradiol in trans women by route of administration and dose*
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