Endocrine Abstracts

Background: The standard approach for Gender-Affirming Hormone Therapy (GAHT) of transgender women (TW) in Israel is oral estradiol (OE) combined with the potent anti-androgen cyproterone acetate (CA). Recently, many of our non-binary patients have requested sublingual estradiol (SLE) without CA, under the unproven belief it preserves erectile function, and does not induce depression. Preliminary data in a few subjects, who self-practiced this approach, suggested it also maintained higher testosterone levels.

Hypothesis: By not suppressing testosterone (T) as profoundly, SLE should be less detrimental to sexual function, and might be superior to OE for improving dysphoria.

Study design: A 6 months controlled, unblinded and non-randomized, prospective study of treatment-naïve TW seeking GAHT.

Patients and Methods: 22 healthy, treatment-naive TW. The SLE arm consisted of 0.5 mg of estradiol 4 times a day, while the OE consisted of oral 2 mg estradiol together with 10 mg CA once daily. Subjects underwent exhaustive chemical, hematologic and hormonal laboratory assessments, and body composition analysis 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 chose SLE, were older 26.3±5.8, vs. 20.1±2.3 yr for OE (P=0.006). Baseline testosterone 19.5±6.8 nmol/l; estradiol 113.3±32.7 pmol/l; LH 4.3±1.4 IU/l; FSH 4.5±3.4 IU/l; and prolactin 226±150 mIU/l were identical between the groups. By paired comparisons, GAHT generated significant, and expected changes at 6 months in both 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 a decrease in lean body mass in both groups. At 6 months, the only differences between the treatment groups were higher estradiol, 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 desire and function decreased significantly with both treatments, and were not spared by the SLE protocol.

Conclusions: GAHT of TW with SLE over 6 months, offers no clear advantage over the standard OE approach that includes CA, neither in hormonal, biochemical and body composition variables, while it generates recurring supraphysiological estradiol concentrations throughout the day, the safety of which, particularly with respect to thrombogenicity, remains to be determined.