Effect of Estrogen Treatment on Drug Metabolism and Transport

Study Overview
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Brief Summary
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This project will evaluate the effect of gender-affirming estrogen treatment on how other medications are processed by the body.

Detailed Description
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Gender-affirming hormone therapy may include estradiol, a hormone that the body creates and uses naturally. Estradiol is prepared as a medication that patients may take to increase hormone levels. Changes in estradiol concentrations in the body may affect how the body processes other medicines. The purpose of this study is to find out how estradiol therapy affects a single tracer dose of approved medicines in the blood (midazolam, digoxin, and acetaminophen) and to confirm estradiol treatment does not affect natural bacterial in the gut.

Official Title
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Effect of Gender-Affirming Estrogen Therapy on Drug Metabolism, Transport, and Gut Microbiota

Conditions
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Transgender Persons

Intervention / Treatment
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* Drug: Midazolam oral solution
* Drug: Digoxin Oral Tablet
* Drug: Acetaminophen Oral Tablet
* Drug: Midazolam Injectable Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self-identified trans* adult 18-55 years of age. Not taking estradiol treatment currently. Planning to start injectable estradiol or estradiol tablets for gender-affirming medical care. Exclusion Criteria: Unwilling/unable to return for project follow-up visits. Unwilling/unable to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Midazolam oral solution|2 mg single-dose before and during estradiol treatment.|
|Drug: Digoxin Oral Tablet|0.25 mg single-dose before and during estradiol treatment.|
|Drug: Acetaminophen Oral Tablet|500 mg single-dose before and during estradiol treatment.|
|Drug: Midazolam Injectable Solution|1 mg intravenous single-dose before and during estradiol treatment.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| midazolam AUC ratio (treatment/control) | ratio of the area under of the plasma concentration time curve (AUC) of midazolam in the presence to absence of gender-affirming estradiol treatment. | 0-6 hours | 
| digoxin renal clearance (treatment/control) | ratio of digoxin renal clearance in the presence to absence of gender-affirming estradiol treatment. | 0-48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| midazolam Cmax ratio (treatment/control) | ratio of the maximum plasma concentration (Cmax) of midazolam in the presence to absence of gender-affirming estradiol treatment | 0-6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone therapy, estrogen treatment