Transgender Estradiol Affirming Therapy

NCT05010707 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202104092
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Transgenderism

Keywords

Transgender female; Gender affirming hormone therapy; Estrogen therapy

Outcome Measures

Primary Outcomes (3)

• Total Testosterone Level in Transgender Female Patients

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

  Change from baseline total testosterone level at 1 and 6 months

• Estradiol Level in Transgender Female Patients

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

  Change from baseline estradiol level at 1 and 6 months

• Estrone Level in Transgender Female Patients

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

  Change from baseline estrone level at 1, and 6 months

Study Arms (3)

Transdermal estradiol plus spironolactone

ACTIVE COMPARATOR

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; Diagnostic Test: Pro-thrombotic markers; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: Spironolactone

Daily sublingual estradiol plus spironolactone

ACTIVE COMPARATOR

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; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: Daily Sublingual Tablet; Drug: Spironolactone

Twice daily sublingual estradiol plus spironolactone

ACTIVE COMPARATOR

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; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: BID Sublingual Tablet; Drug: Spironolactone

Interventions

Transdermal patch DRUG

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

Also known as: Daily

Transdermal estradiol plus spironolactone

Pro-thrombotic markers DIAGNOSTIC_TEST

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.

Daily sublingual estradiol plus spironolactone; Transdermal estradiol plus spironolactone; Twice daily sublingual estradiol plus spironolactone

Metabolic markers DIAGNOSTIC_TEST

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.

Daily sublingual estradiol plus spironolactone; Transdermal estradiol plus spironolactone; Twice daily sublingual estradiol plus spironolactone

Hormone Profile DIAGNOSTIC_TEST

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.

Daily sublingual estradiol plus spironolactone; Transdermal estradiol plus spironolactone; Twice daily sublingual estradiol plus spironolactone

Daily Sublingual Tablet DRUG

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

Also known as: Once daily dosing

Daily sublingual estradiol plus spironolactone

BID Sublingual Tablet DRUG

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

Also known as: Twice daily dosing

Twice daily sublingual estradiol plus spironolactone

Spironolactone DRUG

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

Also known as: Daily

Daily sublingual estradiol plus spironolactone; Transdermal estradiol plus spironolactone; Twice daily sublingual estradiol plus spironolactone

Eligibility Criteria

• Age: 18 Years - 30 Years
• Gender Eligibility Details: Female gender identity
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University Transgender Center

St Louis, Missouri, 63112, United States

Location

Related Publications (11)

• Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016 Dec;5(6):877-884. doi: 10.21037/tau.2016.09.04.

  PMID: 28078219 BACKGROUND

• Kaltiala-Heino R, Bergman H, Tyolajarvi M, Frisen L. Gender dysphoria in adolescence: current perspectives. Adolesc Health Med Ther. 2018 Mar 2;9:31-41. doi: 10.2147/AHMT.S135432. eCollection 2018.

  PMID: 29535563 BACKGROUND

• Connolly MD, Zervos MJ, Barone CJ 2nd, Johnson CC, Joseph CL. The Mental Health of Transgender Youth: Advances in Understanding. J Adolesc Health. 2016 Nov;59(5):489-495. doi: 10.1016/j.jadohealth.2016.06.012. Epub 2016 Aug 17.

  PMID: 27544457 BACKGROUND

• Hamidi O, Davidge-Pitts CJ. Transfeminine Hormone Therapy. Endocrinol Metab Clin North Am. 2019 Jun;48(2):341-355. doi: 10.1016/j.ecl.2019.02.001. Epub 2019 Mar 23.

  PMID: 31027544 BACKGROUND

• Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011 Apr;164(4):635-42. doi: 10.1530/EJE-10-1038. Epub 2011 Jan 25.

  PMID: 21266549 BACKGROUND

• Angus LM, Nolan BJ, Zajac JD, Cheung AS. A systematic review of antiandrogens and feminization in transgender women. Clin Endocrinol (Oxf). 2021 May;94(5):743-752. doi: 10.1111/cen.14329. Epub 2020 Oct 5.

  PMID: 32926454 BACKGROUND

• Spanos C, Bretherton I, Zajac JD, Cheung AS. Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: A systematic review. World J Diabetes. 2020 Mar 15;11(3):66-77. doi: 10.4239/wjd.v11.i3.66.

  PMID: 32180895 BACKGROUND

• Bagot CN, Marsh MS, Whitehead M, Sherwood R, Roberts L, Patel RK, Arya R. The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy. J Thromb Haemost. 2010 Aug;8(8):1736-44. doi: 10.1111/j.1538-7836.2010.03953.x. Epub 2010 Jun 14.

  PMID: 20553380 BACKGROUND

• Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-3903. doi: 10.1210/jc.2017-01658.

  PMID: 28945902 BACKGROUND

• Bao AM, Liu RY, van Someren EJ, Hofman MA, Cao YX, Zhou JN. Diurnal rhythm of free estradiol during the menstrual cycle. Eur J Endocrinol. 2003 Feb;148(2):227-32. doi: 10.1530/eje.0.1480227.

  PMID: 12590642 BACKGROUND

• Cortez S, Moog D, Lewis C, Williams K, Herrick C, Fields M, Gray T, Guo Z, Nicol G, Baranski T. Effectiveness and Safety of Different Estradiol Regimens in Transgender Women (TREAT Study): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2023 Dec 22;12:e53092. doi: 10.2196/53092.

  PMID: 38133914 DERIVED

MeSH Terms

Conditions

Transsexualism

Interventions

Transdermal Patch; Spironolactone

Condition Hierarchy (Ancestors)

Sexuality; Sexual Behavior; Behavior

Intervention Hierarchy (Ancestors)

Equipment and Supplies; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Thomas Baranski, MD, PhD
• Organization: Washington University in St. Louis, School of Medicine

baranski@wustl.edu

314-747-3997

Study Officials

• Ginger Nicol, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Child & Adolescent Psychiatry

Model Details: Participants who agreed to be in the study will undergo block randomization into three groups: 1. daily sublingual 17 beta estradiol 2. twice daily sublingual 17 beta estradiol 3. transdermal 17 beta estradiol All patients will also receive spironolactone as antiandrogen.

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: August 18, 2021
• Study Start: August 2, 2021
• Primary Completion: August 1, 2023
• Study Completion: January 1, 2024
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Locations

US (1)