Transgender Estradiol Affirming Therapy (TREAT)

December 2, 2022 updated by: Ginger E Nicol, Washington University School of Medicine

Effectiveness and Safety of Different Estradiol Replacement Therapies in Transgender Female

The purpose of this open label, pilot, randomized clinical trial is to evaluate the effectiveness, safety and tolerability of estrogen use in transgender female and the degree of testosterone suppression achieved in this population when placed on gender affirming pharmacological therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Transgender patients suffer from poor mental and medical health outcomes compared to their cisgender peers. Given the widespread acknowledgment of the health care needs of transgender people, priority should be given to those actions that will ensure safe and appropriate care in health centers.

The current hormone therapy is not uniform and depends on the health care system, cost considerations, and differences in the regional availability of estrogens and antiandrogens. A typical regimen includes estrogen to provide feminizing effects in conjunction with therapy to block testosterone (antiandrogens or gonadotropin-releasing hormone [GnRH] analogs). Estrogen also inhibits testosterone secretion.

Ethinyl estradiol was previously the mainstay of most estrogen-directed therapies; this is no longer the case due to its increased risk of cardiovascular death and increased incidence of deep venous thrombosis. 17-beta estradiol, which can be provided in tablet, patch, and injection, is currently the preferred formulation.

This open label, pilot, randomized clinical trial will evaluate the effectiveness and safety of gender affirming hormone therapy with estrogen and the degree of testosterone suppression achieved in transgender female patients when placed on daily sublingual 17-beta estradiol, twice daily sublingual 17-beta estradiol, or transdermal 17-beta estradiol. All patients will also receive spironolactone as antiandrogen.

One of the major complications from estradiol GAHT is thromboembolism. The investigators will also determine the effects of the different estradiol regimens on thrombosis markers. These studies will be the first to determine if the dosing regimen of estradiol affects risk markers in transgender women.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63112
        • Recruiting
        • Washington University Transgender Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 30 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Female transgender patients between the ages of 18 to 30 years of age who are seen at the Washington University Transgender Center. Patients must have met the eligibility and readiness criteria for gender-affirming hormone therapy.

Exclusion Criteria:

  • GnRH agonist for the last 12 months
  • History of liver disease
  • Dyslipidemia requiring treatment
  • Cigarette smoking
  • Body mass index >30 kg/m2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Transdermal estradiol plus spironolactone

Starting dose will be 100 mcg/24hrs Plan to increase by 100 mcg/24hrs every month to a max dose of 400 mcg/24hrs Goal is to achieve a serum estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels

All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
Drug: Transdermal patch
Participants will be prescribed the medication and dosed based on their hormonal profile. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Diagnostic test: Pro-thrombotic markers
Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.
Diagnostic test: Metabolic markers
Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.
Diagnostic test: Hormone Profile
Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.
Drug: Spironolactone
All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
ACTIVE_COMPARATOR: Daily sublingual estradiol plus spironolactone

Starting dose will be 2 mg daily Plan to increase every month by 2 mg daily Goal is to achieve serum estradiol level between 100-200 pg/mL mL and to suppress testosterone to cisgender female levels.

All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.

Spironolactone will be started at 50 mg daily and will increase to standard dose.
Diagnostic test: Pro-thrombotic markers
Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.
Diagnostic test: Metabolic markers
Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.
Diagnostic test: Hormone Profile
Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.
Drug: Spironolactone
All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
Drug: Sublingual Tablet
Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as once daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Other Names:
  • Once daily dosing
Drug: Sublingual Tablet
Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as twice daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Other Names:
  • Twice daily dosing
ACTIVE_COMPARATOR: Twice daily sublingual estradiol plus spironolactone

Starting dose will be 1 mg twice daily Plan to increase every month by 2 mg daily divided BID Goal is to achieve serum estradiol level between 100-200 pg/mL mL and to suppress testosterone to cisgender female levels

All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.

Spironolactone will be started at 50 mg daily and will increase to standard dose.
Diagnostic test: Pro-thrombotic markers
Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.
Diagnostic test: Metabolic markers
Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.
Diagnostic test: Hormone Profile
Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.
Drug: Spironolactone
All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
Drug: Sublingual Tablet
Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as once daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Other Names:
  • Once daily dosing
Drug: Sublingual Tablet
Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as twice daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Other Names:
  • Twice daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Degree of testosterone suppression by measuring total testosterone level in transgender female patients undergoing hormonal affirming therapy
Time Frame: Change from baseline total testosterone level at 6,12,18, and 24 months
Change from baseline total testosterone level at 6,12,18, and 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Coagulation factors II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance in transgender female patients undergoing
Time Frame: Change from baseline factor II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance level at 6,12,18, and 24 months
Change from baseline factor II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance level at 6,12,18, and 24 months
von Willebrand factor in transgender female patients undergoing
Time Frame: Change from baseline von Willebrand factor antigen level at 6,12,18, and 24 months
Change from baseline von Willebrand factor antigen level at 6,12,18, and 24 months
Llipid panel
Time Frame: Changes from baseline lipid panel at 12 and 24 months
Changes from baseline lipid panel at 12 and 24 months
Homeostatic Model Assessment for Insulin Resistance
Time Frame: Change from baseline HOMA-IR at 6,12,18, and 24 months
Change from baseline HOMA-IR at 6,12,18, and 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 2, 2021

Primary Completion (ANTICIPATED)

January 1, 2024

Study Completion (ANTICIPATED)

January 1, 2024

Study Registration Dates

First Submitted

July 16, 2021

First Submitted That Met QC Criteria

August 10, 2021

First Posted (ACTUAL)

August 18, 2021

Study Record Updates

Last Update Posted (ACTUAL)

December 5, 2022

Last Update Submitted That Met QC Criteria

December 2, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202104092

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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