SUN-504 Effectiveness of Different Estradiol Regimens in Transgender Females (TREAT STUDY): A Randomized Controlled Trial

Abstract S. Cortez: None. T.J. Baranski: None. G. Nicol: None. Background: Current gender-affirming hormone therapy (GAHT) guidelines for transgender women are based on treatments used in postmenopausal women and clinical experience from experts in the field. A major goal of GAHT for transfeminine individuals is to use estradiol therapy to suppress endogenous production of testosterone. However, the effects of different estradiol dosing regimens and route of administration on testosterone suppression are unknown. This study is the first randomized trial comparing different GAHT regimens for optimal estradiol route and dosing.Methods : The primary objective of this open-label, randomized pilot trial was to evaluate 1 month and 6 months total testosterone suppression in treatment-naive transgender women randomized to GAHT with pulsed (once- or twice-daily sublingual 17-beta estradiol) or continuous (transdermal 17-beta estradiol) GAHT. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Transgender women 18 to 45 years of age were eligible to enroll unless they had a history of coagulopathy, cigarette smoking, liver disease, dyslipidemia requiring treatment, or use of GnRH agonist. Results: From a baseline total testosterone level of 495 ng/dL, the transdermal group had the largest reduction, 435.5 ng/dL (SD: 182 ng/dL), followed by a reduction of 220.4 ng/dL (SD: 214.7 ng/dL) for the once-daily 17 beta estradiol and 190 ng/dL (SD: 118.3 ng/dL) in the twice-daily 17 beta estradiol treatment groups, respectively. Significance between-group differences were noted between the transdermal and twice daily (mean difference -250.6 ng/dL [95% CI, -54.2 to -447.1] P<0.009), and transdermal patch and once daily sublingual preparations (-225.3 ng/dL [95% CI, -28.8 to -421.7], P<0.02). Following 6 months of GAHT no between-group differences were detected. The estrone levels in the transdermal arm are significantly different from the other treatment arms at 1 and 6 months. There were not significant in between- group differences in estradiol levels at 1 and 6 months. At 6 months, the average 17 beta estradiol dose for the once daily, twice daily, and the transdermal were, 6.2 mg/day (range: 2 to 10 mg/day), 6.2 mg/day divided BID (range: 4 to 12 mg/day), and 0.17 mg/day (range: 0.1- 0.3 mg/day) respectively. Conclusion: Transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cis-female testosterone levels within 2 months on one or two 0.1 mg/24hrs estradiol patches changed twice weekly. Given no difference between once or twice daily sublingual estradiol, pulsed 17-beta estradiol likely provides no additional benefit for testosterone suppression compared to oral estradiol. Sunday, June 2, 2024