VA policy released 3/17/25 to phase out treatment for gender dysphoria

The study will test:

1. whether estrogen treatment in transwomen is associated with improved insulin sensitivity and beta cell function
2. whether testosterone treatment in transmen is associated with worsening insulin sensitivity and beta cell function
3. whether estrogen therapy leads to enhanced immune response in older transwormen

All subjects will participate in a 2-hour oral glucose tolerance test (OGTT) and DXA scan for estimation of lean body mass. Only the transgender subjects will have a repeat OGTT two weeks after discontinuation of Gender Affirming Hormone Therapy (GAHT).

Beta cell function will be correlated with the Estrogen/Testosterone ratio to evaluate the relationship between sex hormones and beta cell function. Plasma Glucagon-like peptide 1 (GLP-1) response during the OGTT will be measured to evaluate if estrogen treatment modulates insulin secretion by increasing GLP-1 secretion.

Inclusion Criteria:

• Healthy volunteers: healthy male or female
• MTF transgender
• FTM transgender
• Non-diabetic (A1c<6.5%), fasting glucose <126mg/dl and OGTT after 2 hr <200mg/dl)
• Stable hormone treatment (estrogen or testosterone) for at least 6 months

Exclusion Criteria:

• History of or newly diagnosed diabetes mellitus
• For healthy volunteers, not current treatment with estrogen or testosterone
• For FTM transgender, no recent cardiovascular event: acute coronary syndrome (ACS), stroke (CVA)
• For MTF and FTM transgender, less than 6 months of stable hormone treatment
• Anemia with hemoglobin (Hb) <11.0 hematocrit (Hto) < 34 and Glomerular Filtration rate (GFR) <30