SAT409 Sublingual Estradiol Only, Compared To Combined Oral Estradiol And Cyproterone Acetate,Offers No Apparent Advantage For Gender Affirming Hormone Therapy (GHAT), In Treatment Naïve Transwomen: Results Of A Prospective Pilot Study
Authors: Yaish Iris , Gindis Guy , Greenman Yona , Shefer Gabi , Buch Assaf , Arbiv Mira , Moshe Yaffa , Sofer Yael , Tordjman Karen Michele 
Published: October 2023

Abstract
Disclosure: I. Yaish: None. G. Gindis: None. Y. Greenman: None. G. Shefer: None. A. Buch: None. M. Arbiv: None. Y. Moshe: None. Y. Sofer: None. K.M. Tordjman: None.
Background: The standard approach for Gender-Affirming Hormone Therapy (GAHT) oftransgender women (TW) in Israel is oral estradiol (OE) combined with the potent antiandrogencyproterone acetate (CA). Recently, many of our non-binary patients haverequested sublingual estradiol (SLE) without CA, under the unproven belief it preserveserectile function, and does not induce depression. Preliminary data in a few subjects, whoself-practiced this approach, suggested it also maintained higher testosterone levels.Hypothesis: By not suppressing testosterone (T) as profoundly, SLE should be lessdetrimental to sexual function, and might be superior to OE for improving dysphoria.Study design: A 6 months controlled, unblinded and non-randomized, prospective study oftreatment-naïve TW seeking GAHT.Patients and Methods: 22 healthy, treatment-naive TW. The SLE arm consisted of 0.5 mg ofestradiol 4 times a day, while the OE consisted of oral 2 mg estradiol together with 10 mg CAonce daily. Subjects underwent exhaustive chemical, hematologic and hormonal laboratoryassessments, body composition assessment at baseline and after 6 months. Furthermore,they completed validated dysphoria, sexual desire and function questionnaires. Results: At baseline, the only difference between the groups was age. Subjects who choseSLE, were older 26.3±5.8, vs. 20.1±2.3 yr for OE (P=0.006). Baseline testosterone 19.5±6.8nmol/L; estradiol 113.3±32.7 pmol/L; LH 4.3±1.4 IU/L; FSH 4.5±3.4 IU/L; and prolactin226±150 mIU/L were identical between the groups.By paired comparisons, GAHT generated significant, and expected changes at 6 months inboth groups: creatinine, hemoglobin, hematocrit, total and LDL cholesterol, testosterone,gonadotropins all decreased, while estradiol and prolactin rose. BMI remained unchanged,but there was a significant increase in fat mass, and decrease in lean body mass in bothgroups. At 6 months, the only differences between the treatment groups were a higherestradiol, and LH in the SLE group: 204.6±63.3 vs. 109.7±53 pmol/L, P=0.02; and 3.5±1.2 vs.1.6±1.3 IU/L, P=0.007, respectively.Median estradiol, 90 minutes after 0.5 mg SLE was 1721 [IQR 1000-2432] pmol/L. Remarkably dysphoria did not improve in either group during the study period. Sexual desireand function decreased significantly with both treatments, and were not spared by the SLEprotocol.Conclusions: GAHT with SLE over 6 months offers no clear advantage over the standard OEapproach that includes CA, neither in hormonal, biochemical and body compositionvariables, while it generates recurring supraphysiological estradiol concentrations during theday, the safety of which, particularly with respect to thrombogenicity, remains to bedetermined.
Presentation: Saturday, June 17, 2023