Effect of Gender Affirming Hormone Therapy on Glucose Metabolism

Early Phase 1

Recruiting

• Conditions: Transgender Persons
• Interventions: Drug: Botnia Clamp; Other: Withdrawal of Gender Affirming Hormone Therapy (GAHT)

• Registration Number: NCT04515472
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

Study Timeline

• Study Start: 2020-06-17
• Study First Submitted: 2020-08-13
• Study First Submitted QC: 2020-08-13
• Study First Posted: 2020-08-17
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-09
• Primary Completion: 2025-06
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Volunteer Male	Botnia Clamp	Healthy male currently on no testosterone treatment
Healthy Volunteer Female	Botnia Clamp	Healthy female currently on no estrogen treatment
MTF group	Botnia Clamp	MTF transgender currently on estrogen treatment
MTF group	Withdrawal of Gender Affirming Hormone Therapy (GAHT)	MTF transgender currently on estrogen treatment
FTM group	Botnia Clamp	FTM transgender group currently on testosterone treatment
FTM group	Withdrawal of Gender Affirming Hormone Therapy (GAHT)	FTM transgender group currently on testosterone treatment

Primary Outcome Measures

Name	Time	Method
Effects of Chronic estrogen therapy on insulin secretion	Baseline to 180 minutes	Change in GLP-1 in response to glucose
Effects of Chronic testosterone therapy on insulin secretion	Baseline to 180 minutes	Change in GLP-1 in response to glucose
Effects of Chronic estrogen therapy on insulin sensitivity	Baseline to 6 months	Change in beta cell function
Effects of Chronic testosterone therapy on insulin sensitivity	Baseline to 6 months	Change in beta cell function

Secondary Outcome Measures

Name	Time	Method
Immune response change	Baseline to 6 months	Withhold GAHT for 2 weeks after Botnia Clamp

Trial Locations

Locations (1)

Bartter Clinical Research Unit, Audie L. Murphy VA Hospital, sTXVHCS; 🇺🇸 San Antonio, Texas, United States