Sex Steroids Regulate Liver Fat Content and Body Fat Distribution in Both Men and Women: A Study in Transgender Persons.

CONTEXT: Liver fat content and visceral fat volume are associated with insulin resistance and cardiovascular disease and are higher in men than in women. OBJECTIVE: To determine the effect of estradiol and testosterone treatment on liver fat and visceral fat in transgender persons. DESIGN: Open-label intervention study (SHAMVA) with a 1-year follow-up. SETTING: Gender clinic in a hospital. PATIENTS: 8 trans women and 18 trans men receiving hormone treatment. INTERVENTIONS: Trans women received an antiandrogen and after 6 weeks estradiol was added. Trans men were randomized to receive triptorelin, testosterone, and anastrozole for 12 weeks or triptorelin and testosterone for 12 weeks, followed by only testosterone until week 52. MAIN OUTCOME MEASURES: Liver fat content, visceral and abdominal subcutaneous fat volume, measured by magnetic resonance spectrometry or imaging at baseline, 6, 8, 18, and 58 weeks in transwomen or at baseline; at 6 and 12 weeks in trans men with anastrozole; and at 52 weeks in trans men without anastrozole. RESULTS: In trans women, liver fat content decreased by 1.55% (-2.99 to -0.12) after 58 weeks, compared to week 6. Visceral fat did not change. In trans men with anastrozole, the liver fat content and visceral fat volume did not change. In trans men without anastrozole, after 52 weeks, liver fat content increased by 0.83% (0.14 to 1.52) and visceral fat volume increased by 34% (16 to 51). CONCLUSIONS: Sex hormones regulate liver fat content and visceral fat in men and women.

The Role of Estrone in Feminizing Hormone Treatment.

CONTEXT: In trans women, hormone treatment induces feminization; however, the degree of feminization varies from person to person. A possible contributing factor could be estrone, a weak estrogen that interferes with the estrogen receptor. OBJECTIVE: We assessed whether estrone is involved in feminization induced by hormone treatment. METHODS: This prospective cohort study, with follow-up of 1 year, included 212 adult trans women at a gender identity clinic, who were starting gender-affirming hormone treatment between July 2017 and December 2019, median age 25 years. Change in fat percentage and breast development were assessed. RESULTS: After 12 months of hormone treatment, estrone concentration was 187 pmol/L (95% CI, 153-220) in transdermal and 1516 pmol/L (95% CI, 1284-1748) in oral estradiol users. Fat percentage increased by 1.2% (interquartile range [IQR], 0.3-4.8) in transdermal and 4.6% (IQR, 2.5-5.9) in oral estradiol users. This was not associated with estrone concentrations in transdermal (+4.4% (95% CI, -4.0 to 13) per 100 pmol/L increase in estrone concentration) nor in oral estradiol users (-0.7% [95% CI, -1.7 to 0.3]). Breast volume increased by 69 mL (IQR, 58-134) in transdermal and 62 mL (IQR, 32-95) in oral estradiol users. This was not associated with estrone concentrations in transdermal (+14% [95% CI, -49 to 156] per 100 pmol/L increase in estrone concentration) nor oral estradiol users (+11% [95% CI -14 to 43]). CONCLUSIONS: Change in fat percentage and breast development in trans women were not associated with estrone concentrations nor with administration route. Therefore, measurement of estrone concentrations does not have a place in the monitoring of feminization in trans women.

Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures.

INTRODUCTION: Hormone treatment induces feminization of the body in transwomen and masculinization in transmen. However, the effect of hormone treatment on facial characteristics is still unknown. AIM: We aimed to study whether hormone treatment induces facial feminization and masculinization and how this potential change affects satisfaction and self-esteem. METHODS: In this single-center cohort study, we included 27 transwomen and 15 transmen who received standardized hormone treatment in the Center of Expertise on Gender Dysphoria, VU University Medical Center Amsterdam. Facial 3-dimensional images were obtained at baseline and at 3 and 12 months. At each image, 22 facial landmarks were placed. Furthermore, the FACE-Q Satisfaction with Facial Appearance Overall and the Rosenberg self-esteem scale were obtained at the same measurement points. MAIN OUTCOME MEASURES: The main outcome measures included the relative local shift of skin in millimeters in the 22 landmarks in the transverse (x-axis), coronal (y-axis), and sagittal (z-axis) anatomic axes, the color maps, and the outcomes of the questionnaires. RESULTS: After 12 months, cheek tissue in transwomen increased, with 0.50 mm (95% CI 0.04-0.96) in the x-axis and 1.08 mm (95% CI 0.31-1.85) in the z-axis. Tissue in the jaws decreased with -0.60 mm (95% CI -1.28-0.08) in the x-axis and -0.18 mm (95% CI -0.03-0.33) in the y-axis. Cheek tissue in transmen decreased with -0.45 mm (95% CI -1.00-0.11) in the x-axis and -0.84 mm (95% CI -1.92-0.25) in the z-axis. These changes already started after 3 months. An increase in satisfaction with the facial appearance was found in both transwomen and transmen. There were no changes in reported self-esteem. CLINICAL IMPLICATION: These results could lead to more realistic expectations of facial changes. Furthermore, our results suggest that the face continues to change for at least a year, which could suggest that performing facial feminization surgery after 1 year of hormone treatment might be too early. STRENGTH & LIMITATIONS: This study is the first that provides insight into the facial changes in transgender individuals receiving hormone treatment, and it introduces an objective method to examine (small) facial changes. Our study is limited by the poor reliability of the landmarks, the difficulty of facial fixation, and the lack of gender-specific questions in the questionnaires. CONCLUSIONS: Hormone treatment in transwomen induces an increase in cheek tissue and a decrease in jaw tissue. In transmen a tendency of decrease in cheek tissue and an increase in jaw tissue was found. These changes are in the direction of the desired gender. Tebbens M, Nota NM, Liberton NPTJ, et al. Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures. J Sex Med 2019;16:746-754.