Transgender Estradiol Affirming Therapy

Transgenderism Clinical Trial

— TREAT  

Official title:

Effectiveness and Safety of Different Estradiol Replacement Therapies in Transgender Female

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05010707
• Other study ID #: 202104092
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2, 2021
• Est. completion date: January 2024

Study information

• Verified date: December 2022
• Source: Washington University School of Medicine
• Contact: Samuel Cortez, MD
• Phone: 314-286-2339
• Email: scortez[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Transgenderism

Intervention

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

Locations

Country	Name	City	State
United States	Washington University Transgender Center	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Clin Endocrinol Metab. 2018 Feb 1;103(2):699. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2758-2759. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Degree of testosterone suppression by measuring total testosterone level in transgender female patients undergoing hormonal affirming therapy		Change from baseline total testosterone level at 6,12,18, and 24 months
Secondary	Coagulation factors II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance in transgender female patients undergoing		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
Secondary	von Willebrand factor in transgender female patients undergoing		Change from baseline von Willebrand factor antigen level at 6,12,18, and 24 months
Secondary	Llipid panel		Changes from baseline lipid panel at 12 and 24 months
Secondary	Homeostatic Model Assessment for Insulin Resistance		Change from baseline HOMA-IR at 6,12,18, and 24 months