Transgender Estradiol Affirming Therapy (TREAT)

The Washington University

Status and phase: Completed; Phase 2

Conditions: Transgenderism

Treatments: Diagnostic Test: Pro-thrombotic markers; Drug: BID Sublingual Tablet; Drug: Daily Sublingual Tablet; Diagnostic Test: Metabolic markers; Drug: Transdermal patch; Drug: Spironolactone; Diagnostic Test: Hormone Profile

Study type: Interventional

Funder types: Other

Identifiers

NCT05010707

202104092

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: Male

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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39 participants in 3 patient groups

Transdermal estradiol plus spironolactone

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Hormone Profile

Drug: Spironolactone

Drug: Transdermal patch

Diagnostic Test: Metabolic markers

Diagnostic Test: Pro-thrombotic markers

Daily sublingual estradiol plus spironolactone

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Hormone Profile

Drug: Spironolactone

Diagnostic Test: Metabolic markers

Drug: Daily Sublingual Tablet

Diagnostic Test: Pro-thrombotic markers

Twice daily sublingual estradiol plus spironolactone

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Hormone Profile

Drug: Spironolactone

Diagnostic Test: Metabolic markers

Drug: BID Sublingual Tablet

Diagnostic Test: Pro-thrombotic markers