MON-192 - Effect of Gender Affirming Therapy on Androgen and Estrogen Receptor Expression in Mononuclear Cells

Background: Testosterone therapy in transgender men (TM) and estrogen therapy in transgender women (TW) respectively are the mainstays of gender affirming hormone therapy (GAHT). However, the effects of GAHT on androgen receptor (AR), Estrogen receptor (ERα) and aromatase enzyme expression have not been described. A change in AR or ERα expression may possibly augment, or serve as a detriment, to the desired effects from GAHT.

Methods: We recruited 14 TW and 9 TM to provide fasting blood samples for the study. Twelve cisgender females (F) and 21 cisgender males (M) were recruited to serve as controls. All study volunteers were 18-50 years of age. Transgender volunteers had been on GAHT continuously for at least 3 months. Cisgender volunteers were not taking any hormone preparations and were not known to have hypogonadism. Serum testosterone and estradiol were measured by liquid chromatography tandem mass spectrometry. Mononuclear cells (MNC) were separated, and expression of AR, ERα and aromatase was measured by real-time reverse transcription–polymerase chain reaction. Results are presented as mean ± standard deviation and comparisons among groups were made by t-test and one-way ANOVA. Gene expression values were normalized to the expression of a group of housekeeping genes including GAPDH and PPIA.

Results: The mean age of volunteers in F, M, TW and TM groups were 31±9, 33±12, 33±9 and 24±7 years respectively. Eight TM volunteers used intramuscular testosterone while one used testosterone gel. Eight TW volunteers used intramuscular estradiol, 6 used oral estradiol while one used transdermal patch. Eight TW volunteers were also taking spironolactone while three were on progesterone. Volunteers in TM and TW groups had used GAHT for 18±22 and 23±17 months respectively. The mean serum testosterone concentrations in F, M, TW and TM groups were 26±18, 484±281, 140±202 and 627±181 ng/dL respectively. The serum testosterone concentrations of TM group were similar to M (p=0.14 by t-test) but higher than TW (p < 0.001 by t-test). The mean serum estradiol concentrations in F, M, TW and TM groups were 142±140, 25±14, 209±324 and 39±19 pg/mL respectively. Serum estradiol concentrations in TW group were similar to F groups (p=0.09 by t-test) and TM groups (p=0.19 by t-test). The expression of AR in F, M, TW and TM groups was 1.2±0.9, 0.9±0.5, 1.0±0.9 and 1.0±0.6 respectively (p= 0.74 by ANOVA). The expression of ERα in F, M, TW and TM groups was 1.2±0.5, 1.1±0.5, 1.4±0.9 and 0.8±0.3 respectively (p= 0.23 by ANOVA). Aromatase expression in F, M, TW and TM groups was 1.4±1.2, 1.2±0.5, 2.5±2.9 and 1.2±0.8 respectively (p= 0.12 by ANOVA).

Conclusion: The expression of AR, ERα and aromatase in peripheral MNC was not affected by GAHT. This does not rule out tissue specific changes in the expression of sex steroid receptors, especially in hormone sensitive tissues such as skeletal muscle for AR and adipose tissue for ERα.

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