Endocrine Abstracts

Background and Aim: We previously demonstrated that low-dose estradiol (E2) administered sublingually alone for 6 months in treatment-naïve trans women (TW), suppressed testosterone to the same degree, but generated higher serum E2 levels as the same oral dose combined with cyproterone acetate. We now sought to assess the possible differential impact of these approaches on anthropometric and body composition measurements, sex-dependent indicators with proven metabolic prognostic value.

Methods: 22 treatment-naïve TW, 23.2±1.1 y, opted non-randomly, in a 1:1, ratio to receive sublingual E2 (2 mg divided into 4 daily doses), or oral 2 mg E2+10 mg cyproterone acetate for 6 months (6M). Anthropometric, hormonal, and body composition by DXA (Lunar Prodigy-GE) measurements were obtained at baseline, and after 6M of GAHT.

Results: Anthropometric, body composition measurements, and testosterone at baseline and 6M did not differ between the groups. In a first step, all subjects were analyzed together for assessment of the general impact of GAHT. By paired comparisons, neither weight nor BMI had changed at 6M. Hip circumference remained unchanged, however, waist circumference decreased by 2.7±1.19 cm (P=0.047), resulting in a significant reduction in waist-to-hip-ratio (P=0.018). The total regional fat percentage increased from 23.4±2.3% to 27.8±1.8% (P<0.001). This increase was significant for all fat depots (gynecoid, arms, legs, trunk) except for the android area. Total body fat mass increased by 2.6 kg, from 18.4±2.4 to 21.0±2.4 kg (P=0.008). In contrast, subjects lost lean mass in all compartments. The whole body lean mass loss was 3.4±0.3 kg (a 21.6% decrease, P<0.001), leading to a decrease in the lean/fat mass ratio from 4.7 to 2.9, (P=0.0002). Analyzed separately, some changes appeared to be influenced by the treatment route, particularly the increases in fat depots that were significantly milder in the sublingual group. The lean body mass decrease, however, was similar with both treatments. After age-adjustment, none of the variables at 6M correlated with hormone levels. However, decreases in total body, legs, and arms lean mass were inversely correlated with testosterone at 6M (r=-0.41, P=0.045; r=-0.476, P=0.033; and r=-0.563, P=0.01, respectively).

Conclusions: A relatively short GAHT period with a low dose of E2 generated significant body feminization in TW. Subjects in the sublingual group were surprisingly spared from body fat accumulation. The reason for this differential effect of sublingual E2 is still unknown. Sublingual E2 could offer some protection from fat accumulation but not from lean body mass loss in TW.