The following is a summary of “Changes in Serum Testosterone and Adrenal Androgen Levels in Transgender Women With and Without Gonadectomy,” published in the February 2023 issue of Endocrinology & Metabolism by Collet, et al.

The use of feminizing gender-affirming hormone therapy (GAHT) in transgender women is known to significantly reduce serum testosterone levels. However, it was uncertain whether testosterone levels continued to decline and if there were changes in adrenal androgen levels during and after GAHT and gonadectomy. The lack of information created difficulties in clinical decision-making for transgender women experiencing symptoms attributed to GAHT or gonadectomy.

To address these uncertainties, a study was conducted on 275 transgender women who underwent estradiol and cyproterone acetate (CPA) therapy, with follow-up visits after 3 months, 12 months, and 2 to 4 years. Of these, almost half underwent gonadectomy. The levels of total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (A4) were measured using liquid chromatography-tandem mass spectrometry.

The study found that following 3 months of GAHT, the mean TT, calculated free testosterone (cFT), and A4 levels decreased by 18.4 nmol/L (95% CI, −19.4 to −17.4, P < 0.001 [equivalent to a reduction of 97.1%]), 383 pmol/L (95% CI, −405 to −362, P < 0.001 [equivalent to a reduction of 98.3%]), and 1.2 nmol/L (95% CI, −1.4 to −1.0, P < 0.001 [equivalent to a reduction of 36.5%]), respectively. However, these levels remained stable after that. The levels of DHEA and DHEAS decreased by 7.4 nmol/L (95% CI, −9.7 to −5.1 [equivalent to a reduction of 28.0%]) and 1.8 µmol/L (95% CI, −2.2 to −1.4 [equivalent to a reduction of 20.1%]), respectively, after 1 year but remained stable after that. After gonadectomy, the cessation of CPA therapy did not result in any further changes in TT, cFT, DHEA, DHEAS, and A4 levels compared to those who did not undergo gonadectomy.

In conclusion, the study affirmed that while testosterone levels decline significantly in the initial stages of GAHT, they remain stable. Adrenal androgens decrease in the first year of CPA and estrogen supplementation and remain unchanged after gonadectomy. No androgen levels were changed after gonadectomy and cessation of CPA therapy. The implications of the findings on clinical symptoms required further investigation.

Reference: academic.oup.com/jcem/article/108/2/331/6750024