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TransgenderismPhase 2TREATNCT05010707

Transgender Estradiol Affirming Therapy

A Phase 2 study testing Transdermal patch, Pro-thrombotic markers and Metabolic markers in people with Transgenderism, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 30 years, men onlyHealthy volunteers can take part
Conditions the study is for
Transgenderism
What is being tested?
Transdermal patch, Pro-thrombotic markers and Metabolic markers
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
2 Aug 2021to 1 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 30 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University Transgender Center

    St Louis, Missouri, 63112

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions
Transgenderism
Being tested
Transdermal patch, Pro-thrombotic markers, Metabolic markers, Hormone Profile, Daily Sublingual Tablet
Keywords
Transgender female, Gender affirming hormone therapy, Estrogen therapy
Medical subject headings
Transsexualism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transdermal patchDrug

    Also called Daily

    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

  • Pro-thrombotic markersDiagnostic 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.

  • Metabolic markersDiagnostic 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.

  • Hormone ProfileDiagnostic 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 TabletDrug

    Also called Once daily dosing

    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

  • BID Sublingual TabletDrug

    Also called Twice daily dosing

    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

  • SpironolactoneDrug

    Also called Daily

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

Study groups in NCT05010707
Study groupRoleWhat they receive
Transdermal estradiol plus spironolactoneActive comparatorStarting 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.
Receives: Drug: Transdermal patch; Diagnostic Test: Pro-thrombotic markers; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: Spironolactone
Daily sublingual estradiol plus spironolactoneActive comparatorStarting 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.
Receives: Diagnostic Test: Pro-thrombotic markers; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: Daily Sublingual Tablet; Drug: Spironolactone
Twice daily sublingual estradiol plus spironolactoneActive comparatorStarting 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.
Receives: Diagnostic Test: Pro-thrombotic markers; Diagnostic Test: Metabolic markers; Diagnostic Test: Hormone Profile; Drug: BID Sublingual Tablet; Drug: Spironolactone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Change from baseline total testosterone level at 1 and 6 months

  2. Estradiol Level in Transgender Female Patients

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

    Measured: Change from baseline estradiol level at 1 and 6 months

  3. Estrone Level in Transgender Female Patients

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

    Measured: Change from baseline estrone level at 1, and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2021
  2. Study start2 Aug 2021
  3. Primary completion1 Aug 2023
  4. Study completion1 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05010707
Sponsor's protocol ID
202104092
Acronym
TREAT
Status last verified
Nov 2024
First submitted
16 Jul 2021
Last updated
26 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

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

    PubMed 28078219

  • 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.

    PubMed 29535563

  • 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.

    PubMed 27544457

  • 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.

    PubMed 31027544

  • 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.

    PubMed 21266549

  • 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.

    PubMed 32926454

  • 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.

    PubMed 32180895

  • 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.

    PubMed 20553380

  • 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.

    PubMed 28945902

  • 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.

    PubMed 12590642

  • 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.

    PubMed 38133914

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Transdermal patch, Pro-thrombotic markers and Metabolic markers in people with Transgenderism, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Testosterone Level in Transgender Female Patients (time frame: Change from baseline total testosterone level at 1 and 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05010707, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.

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