Effect of Estrogen Treatment on Drug Metabolism and Transport

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05469204

Enrollment

Registered

2022-07-21

Start date

2022-11-01

Completion date

2025-07-30

Last updated

2026-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Transgender Persons

Keywords

hormone therapy, estrogen treatment

Brief summary

This project will evaluate the effect of estrogen treatment on how other medications are processed by the body.

Detailed description

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.

Interventions

DRUGMidazolam oral solution

2 mg single-dose before and during estradiol treatment.

DRUGDigoxin Oral Tablet

0.25 mg single-dose before and during estradiol treatment.

DRUGAcetaminophen Oral Tablet

500 mg single-dose before and during estradiol treatment.

DRUGMidazolam Injectable Solution

1 mg intravenous single-dose before and during estradiol treatment.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Secondary

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

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026