OR31-05 Long-Term Effects Of Gender Affirming Hormone Therapy On Insulin Sensitivity, Insulin Secretion, And Glucose Tolerance

Disclosure: S. Pinkson: None. J. Trejo: None. A. Mendoza: None. L. Gondin Hernandez: None. S. Chen: None. S. ahuja: None. D. Tripathy: None. Over the past 15 years, transgender veterans seeking Gender Affirming Hormone Therapy (GAHT) have increased significantly. The metabolic effects of long-term GAHT have been controversial possibly because of multiple confounding factors and different methodologies. We examined long-term effects of estradiol and testosterone on insulin sensitivity and insulin secretion in nondiabetic transwomen and transmen. A total of 4 groups (i) 7 transwomen (age 50 ± 4 yr, BMI 31 ± 2 kg/m(2)) (ii) 6 transmen (age 38 ± 4yr, BMI 33 ± 2 mg/m(2)) followed for 52 ± 9 months and as a control group (iii) six cisgender men (age 36 ± 4 yrs, BMI 32 ± 2 kg/m(2)) and (iv) 8 cisgender women (age 39 ± 4 yr, BMI 28 ± 2 kg/m(2)) participated in an OGTT and Botnia clamp (IV glucose tolerance test: IVGTT followed by hyperinsulinemic (80 mU.m(2)/min euglycemic clamp). Total testosterone (by equilibration dialysis method), estradiol, sex hormone binding globulin (SHBG) and lipid profile was measured in all subjects. Insulin, and C-peptide were measured every 30 min during the OGTT. Insulin sensitivity was measured as the M-value form last 30 minutes of insulin clamp and as Matsuda index of insulin sensitivity from the OGTT. Indices of insulin secretion (data pending) was calculated as the first phase insulin response from IVGTT (FPIR: 2-10min) and as indices of beta cell function from OGTT: Insulin secretion/insulin resistance index (Insulin (0-120)/Glucose (0-120) X Matsuda index). Plasma estradiol in transwomen was 209 ± 92 pg/ml vs. 32 ± 6 pg/ml in cisgender men. Similarly, the total testosterone level in transmen was 319 ± 57 vs. 19 ± 4 ng/dl in cisgender women. There was no difference in SHBG levels between the groups. The body fat content was not different between trans or cis men (36 ± 3 vs 35 ± 1.4 % ) while it was higher in trans vs cis women (40 ± 0.8 vs 30 ± 3%). There was no difference in HbA(1c) (5.4 ± 0.2 vs 5.2 ± 0.2%, p=ns) between transwomen and cismen and (5.6 ± 0.1 vs 5.5 ± 0.1, p=ns) transmen and ciswomen. The glucose AUC was higher in transmen vs cisgender women (5,487 ± 994 vs. 3,420 ± 533; P < 0.05). There was no difference in glucose AUC between the transwomen and cismen. There was no difference in insulin sensitivity (M-value) between transwomen and cisgender men (6.9 ± 1.2 vs 7.0 ± 1.4 mg.kg/min, p=ns), while it tended to be worse in transmen compared to cisgender women ( 6.03 ± 1.0 vs 7.7± 0.6 mg.kg/min, p=0.1). In both groups M-Value was inversely related to BMI (r=-0.59; p<0.05). There was no relationship between insulin sensitivity and plasma total testosterone level. HDL cholesterol was lower in transmen (41 ± 2.5 vs 55 ± 4 mg/dL, p<0.05) versus cisgender women though there was no difference in triglyceride, total or LDL cholesterol between the groups. In conclusion long-term GAHT therapy does not adversely affect insulin sensitivity in trans men or women and the mildly altered glucose tolerance is likely a result of higher BMI in transmen. Presentation: Sunday, June 18, 2023