SUN-126 Fasting Total Ghrelin and Hunger Differ Across Sex and Gender in Adults: A Cross-Sectional Study

Abstract Disclosure: J. Taormina: None. M. Bolt: None. M. Cornier: None. K.L. Moreau: None. M.E. Wierman: None. M.S. Rothman: None. K.T. Legget: None. J.R. Tregellas: None. A.K. Hild: None. D.B. Hammond: None. A. Gebregzabheir: None. M.P. Mancuso: None. M.D. Sammel: None. S.J. Iwamoto: None. Introduction: Plasma ghrelin is central to homeostatic control of hunger and is inversely correlated with total body weight and body fat percentage (BF%). Cisgender (cis) women have higher plasma ghrelin than cis men, and ghrelin is positively associated with serum estradiol in cis women and testosterone in cis men. Estradiol-based gender-affirming hormone therapy (GAHT) use in transgender (trans) women and testosterone-based GAHT use in trans men are associated with body weight increases and differential body composition changes. The association of GAHT with fasting total ghrelin and hunger in trans adults is understudied and may suggest one mechanism for weight and body composition changes observed with GAHT. Specific aim: To evaluate differences in fasting total ghrelin and hunger in adults across sex and gender. Hypothesis: Fasting total ghrelin and hunger are more similar by sex than by gender. Methods: Nonsmoking trans adults on GAHT for >1 year (no gonadectomy) and cis adults (no hypogonadism) participated in a cross-sectional study with fasting total ghrelin and insulin measurements, appetite-related questionnaires (visual analog scale [VAS] for hunger and satiety; Food Cravings Questionnaire-State Version [FCQ-S]), and dual-energy x-ray absorptiometry to measure BF%, after an overnight fast. Multivariable linear regression models examined differences between groups while adjusting for pre-specified covariates (age, BF%, fasting insulin). Results: Among 110 mostly white, non-Hispanic adults (48 cis women, 12 cis men, 34 trans women, 16 trans men), mean (±SD) ages were 39 (10), 39 (10), 44 (17) and 30 (8) years; mean BF% were 43 (4), 30 (4), 35 (8) and 30 (7) %; and mean fasting insulin levels (reference 0-20 uIU/mL) were 15 (7), 18 (9), 6 (4) and 4 (3) uIU/mL, respectively. In regression modeling, fasting total ghrelin was different in trans women (by -341.7 pg/mL, 95% CI [-520.1, -163.3], p < 0.001) and cis men (by -306.0 pg/mL, 95% CI: [-561.1, -51.0], p = 0.02) compared to cis women. Trans women, trans men, and cis men had similar ghrelin levels. Hunger VAS was different for all groups compared to cis women (trans men by -17.9 mm, 95% CI: [-34.9, -0.9], p = 0.04; trans women by -25.9 mm, 95% CI: [-38.3, -13.4], p < 0.001; cis men by -21.5 mm, 95% CI: [-39.4, -3.6], p = 0.02). Trans women, trans men and cis men had similar hunger VAS. Trans and cis adults scored similarly on satiety VAS and FCQ-S. Conclusions: Among trans women, lower fasting total ghrelin and hunger compared to cis women may be attributed to sex recorded at birth rather than estradiol-based GAHT use. Testosterone-based GAHT use may decrease hunger behavior but not fasting total ghrelin compared to pre-GAHT baseline. Future prospective studies can elucidate the impacts of sex recorded at birth, gender, and sex hormones on these and other hormonal and behavioral factors responsible for appetite regulation. Presentation: Sunday, July 13, 2025