Effect of Gender Affirming Hormone Therapy on Glucose Metabolism

NCT ID: NCT04515472

Last Updated: 2025-07-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-17
• Study Completion Date: 2025-03-17

Brief Summary

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

Detailed Description

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.

Conditions

Transgender Persons

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Volunteer Male

Healthy male currently on no testosterone treatment

Group Type: ACTIVE_COMPARATOR

Botnia Clamp

Intervention Type: DRUG

This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.

Healthy Volunteer Female

Healthy female currently on no estrogen treatment

Group Type: ACTIVE_COMPARATOR

Botnia Clamp

Intervention Type: DRUG

This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.

MTF group

MTF transgender currently on estrogen treatment

Group Type: ACTIVE_COMPARATOR

Botnia Clamp

Intervention Type: DRUG

This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.

Withdrawal of Gender Affirming Hormone Therapy (GAHT)

Intervention Type: OTHER

GAHT, either estrogen or testosterone therapy will be withdrawn after the Botnia Clamp.

FTM group

FTM transgender group currently on testosterone treatment

Group Type: ACTIVE_COMPARATOR

Botnia Clamp

Intervention Type: DRUG

This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.

Withdrawal of Gender Affirming Hormone Therapy (GAHT)

Intervention Type: OTHER

GAHT, either estrogen or testosterone therapy will be withdrawn after the Botnia Clamp.

Interventions

Botnia Clamp

This clamp technique is designed to obtain independent measures of insulin secretion and insulin sensitivity during the same test. In brief, 0.3g/kg body wt of a 20% glucose solution is given at time 0. Blood samples for the measurement of plasma glucose and serum insulin are obtained at -10, 0, 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 120, and 180 min.

Intervention Type: DRUG

Withdrawal of Gender Affirming Hormone Therapy (GAHT)

GAHT, either estrogen or testosterone therapy will be withdrawn after the Botnia Clamp.

Intervention Type: OTHER

Other Intervention Names

Glucose solution and insulin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Foundation for Advancing Veterans' Health Research

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Devjit Tripathy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health San Antonio

Locations

Bartter Clinical Research Unit, Audie L. Murphy VA Hospital, sTXVHCS

San Antonio, Texas, United States

Countries

United States

Other Identifiers

HSC20190415H

Identifier Type: -

Identifier Source: org_study_id