MedPath

Transgender Estradiol Affirming Therapy

Phase 2
Completed
Conditions
Transgenderism
Interventions
Diagnostic Test: Pro-thrombotic markers
Drug: Transdermal patch
Diagnostic Test: Metabolic markers
Diagnostic Test: Hormone Profile
Drug: Daily Sublingual Tablet
Drug: BID Sublingual Tablet
Drug: Spironolactone
Registration Number
NCT05010707
Lead Sponsor
Washington University School of Medicine
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
39
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.
Read More
Exclusion Criteria
  • GnRH agonist for the last 12 months
  • History of liver disease
  • Dyslipidemia requiring treatment
  • Cigarette smoking
  • Body mass index >30 kg/m2
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Daily sublingual estradiol plus spironolactonePro-thrombotic markersStarting 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.
Daily sublingual estradiol plus spironolactoneMetabolic markersStarting 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.
Daily sublingual estradiol plus spironolactoneHormone ProfileStarting 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.
Daily sublingual estradiol plus spironolactoneDaily Sublingual TabletStarting 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.
Daily sublingual estradiol plus spironolactoneSpironolactoneStarting 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.
Twice daily sublingual estradiol plus spironolactonePro-thrombotic markersStarting 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.
Twice daily sublingual estradiol plus spironolactoneMetabolic markersStarting 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.
Twice daily sublingual estradiol plus spironolactoneHormone ProfileStarting 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.
Transdermal estradiol plus spironolactoneTransdermal patchStarting 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.
Transdermal estradiol plus spironolactonePro-thrombotic markersStarting 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.
Transdermal estradiol plus spironolactoneMetabolic markersStarting 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.
Transdermal estradiol plus spironolactoneHormone ProfileStarting 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.
Transdermal estradiol plus spironolactoneSpironolactoneStarting 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.
Twice daily sublingual estradiol plus spironolactoneBID Sublingual TabletStarting 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.
Twice daily sublingual estradiol plus spironolactoneSpironolactoneStarting 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.
Primary Outcome Measures
NameTimeMethod
Total Testosterone Level in Transgender Female PatientsChange from baseline total testosterone level at 1 and 6 months

Degree of testosterone suppression by measuring total testosterone level in transgender female patients undergoing hormonal affirming therapy, clinical testosterone level in pg/mL

Estradiol Level in Transgender Female PatientsChange from baseline estradiol level at 1 and 6 months

Degree of testosterone suppression by measuring estradiol level in transgender female patients affirming hormone therapy

Estrone Level in Transgender Female PatientsChange from baseline estrone level at 1, and 6 months

Degree of testosterone suppression by measuring estrone level in transgender female patients affirming hormone therapy

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Washington University Transgender Center

🇺🇸

Saint Louis, Missouri, United States

Washington University Transgender Center
🇺🇸Saint Louis, Missouri, United States
Samuel Cortez, MD
Contact
scortez@wustl.edu
314-286-2339
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