Coagulation and Fibrinolysis of Estradiol in Transwomen

Transgenderism Clinical Trial

Official title:

Coagulation Activation and Fibrinolysis With Sublingual Versus Oral Versus Transdermal Estradiol in Transgender Women

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05387577
• Other study ID #: PRO00036346
• Status: Terminated
• Phase: Early Phase 1
• Start date: December 7, 2021
• Est. completion date: November 23, 2022

Study information

• Verified date: December 2022
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The specific aim for our study is to measure coagulation system activation and fibrinolysis following transdermal versus sublingual versus oral estradiol versus in transgender women.

Hypothesis: Transdermal estradiol will result in less coagulation system activation and no effect on plasminogen activator inhibitor (PAI-1) or tissue-type plasminogen activator (t-PA). Oral estradiol will result in the most coagulation system activation and effect on PAI-1 and t-PA: Oral estradiol > sublingual estradiol > transdermal estradiol.

A prospective crossover study will include ten subjects given estradiol 1 mg daily and instructed to take it orally, sublingually, or transdermal for 2 months with a 2-week washout period between routes of administration. Labs will be measured 7 times during the study.

Description:

Subjects will report to our Adult Translational Research Unit for labs at baseline (2 weeks after HRT washout if needed). Both fibrinolysis and testosterone labs have a diurnal variation. Therefore, fasting labs will be drawn at approximately 8 AM. Five subjects will start oral estradiol and 5 will start sublingual estradiol for 8 weeks. Froedtert's Pharmacy Investigational Drug Service will provide the study estradiol. There will be a 2-week washout period between treatment periods. Fasting labs will be drawn at approximately 8 AM prior to Treatment Period 2. The groups will switch therapy. Those that took oral estradiol during Treatment Period 1 will take sublingual estradiol for 8 weeks. Those that took sublingual estradiol during Treatment Period 1 will take oral estradiol for 8 weeks. Finally, all subjects will start the transdermal for 8 weeks for Treatment Period 3. Final set of labs will be drawn at approximately 8 AM 2 weeks after Treatment Period 3. The investigators will call subjects every 2 weeks to assess their adherence to the treatment protocol and remind them of the importance of allowing the tablet to dissolve when taking estradiol sublingually.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: November 23, 2022
• Est. primary completion date: November 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older

• Gender identity of male to female or transwoman

Exclusion Criteria:

• Liver disease

• History of blood clot

• Bleeding disorder

• Active or recent (e.g., within the past year) stroke

• Myocardial infarction,

• History of orchiectomy

• History of breast cancer,

• Known sensitivity or allergy to any components of the medications used

• Currently taking a potent CYP3A4 inhibitor or inducer.

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Clotting Disorder
• Hemostatic Disorders
• Transgenderism

Intervention

Drug:
• Estradiol Tablets
Oral estradiol will be taken sublingually, 1 mg BID for 8 weeks
• Transdermal patch
Estradiol patch therapy for 8 weeks
• Estradiol Tablets
Oral estradiol 1 mg BID for 8 weeks

Locations

Country	Name	City	State
United States	Froedtert Hospital	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coagulation system activation and fibrinolysis due to estradiol administration	Comparison of morning fasting labs (fibrinogen, von-Willebrand Factor (vWF) ristocetin cofactor, vWF antigen, D-dimer, protein C activity, free protein S activity, Factors VII, VIII, IX, thrombin generation, plasminogen activator inhibitor (PAI-1), tissue-type plasminogen activator (t-PA) and t-PA activity) in transgender women taking estradiol via different routes of administration. Our hypothesis is that transdermal estradiol will result in less coagulation system activation and no effect on PAI-1 or t-PA. Oral estradiol will result in the most coagulation system activation and will effect PAI-1 and t-PA: Oral estradiol > sublingual estradiol > transdermal estradiol.	8 months
Secondary	Thrombotic risk due to estradiol administration	Thrombotic risk will be assessed in transgender women by measuring estrone and thrombin generation and comparing them between the different routes of estradiol administration (transdermal versus sublingual versus oral).	8 months