A-144 Assessment of hormone concentrations post-initiation of exogenous hormone therapies

Abstract

Exogenous hormones are administered to supplement or replace deficient natural hormones and are used in a variety of indications, including hormone replacement therapy, gender-affirming care, and infertility treatment, among others. Therapeutic hormones for gender affirmation are generally assessed based on an individual patient’s goals. Changes in estrogen, testosterone, and gonadotropin concentrations following the initiation of exogenous hormone therapies are incompletely understood, primarily due to a lack of standardized prospective studies. The purpose of this study was to evaluate the detailed, short-term hormonal changes among individuals assigned male at birth initiating feminizing hormonal therapies. This evaluation was conducted as a secondary analysis of a phase I open-label study that investigated the pharmacological interactions between the gonadotropin releasing hormone agonist leuprolide, estradiol and oral tenofovir disoproxil fumarate/emtricitabine (F/TDF), which is used for HIV pre-exposure prophylaxis. Thirteen HIV negative, hormone-naïve/abstinent participants were enrolled. Participants underwent the sequential addition or discontinuation of F/TDF and feminizing hormone therapy over 7 weeks in 6 periods: (1) baseline, (2) F/TDF (300 mg/200 mg po), (3) F/TDF + leuprolide (11.25 mg intramuscular), (4) F/TDF + low-dose estradiol (1 mg po), (5) F/TDF + high-dose (6 mg po) estradiol, and (6) high-dose estradiol without F/TDF. Doses were performed under direct observation. Serum samples were collected weekly, at the end of each study period, to measure hormone concentrations. Estradiol and testosterone (total and free) were measured via liquid chromatography-tandem mass spectrometry. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured using immunoassays. Significant differences in median hormone concentrations between the study periods were assessed using Friedman tests followed by post-hoc pairwise Wilcoxon comparisons. Hormone profiles at baseline and one week after exposure to F/TDF were consistent with those observed in males. Two weeks following leuprolide injection, significant decreases were observed in median levels of FSH (1.02 mIU/mL, p=0.001), LH (2.73 mIU/mL, p=0.011), estradiol (9 pg/mL, p<0.001), and total testosterone (151 ng/dL, p=0.001). After the addition of low-dose exogenous estradiol, further declines in median LH (1.23 mIU/mL, p=0.004) and total testosterone (60.5 ng/dL, p=0.001) were observed; there was an increase in median estradiol back to baseline concentrations (17 pg/mL, p=0.002). One week of a high-dose exogenous estradiol regimen resulted in a significant increase in median estradiol (92 pg/mL, p<0.001) and a further decrease in FSH (0.56 mIU/mL, p=0.003) with no significant differences in LH and total testosterone observed. At the end of the 7-week study, gonadal hormone concentrations were within the ranges for females, with total testosterone concentrations <50 ng/dL and estradiol concentrations between 100-200 pg/mL. Changes in hormone concentrations aligned with expectations from exogenous hormone therapy. FSH showed more significant reductions compared to LH. Further, the dosage of estradiol influenced gonadotropin levels differently, with a low dose significantly impacting LH and a high dose affecting FSH. Lastly, the combination of low-dose estradiol and leuprolide effectively suppressed testosterone but did not increase estradiol into the female benchmark range, but three weeks of high-dose estradiol achieved median concentrations observed in females.