Coagulation and Fibrinolysis of Estradiol in Transwomen

Sponsor

Medical College of Wisconsin (Other)

Overall Status

Recruiting

CT.gov ID

NCT05387577

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Transgenderism Clotting Disorder	Drug: Estradiol Tablets Drug: Transdermal patch Drug: Estradiol Tablets	Early Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 7, 2021

Anticipated Primary Completion Date :

Dec 7, 2023

Anticipated Study Completion Date :

Dec 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sublingual Estradiol Sublingual estradiol administered for 8 weeks	Drug: Estradiol Tablets Oral estradiol will be taken sublingually, 1 mg BID for 8 weeks Other Names: Sublingual estradiol tablets
Active Comparator: Oral Estradiol Oral estradiol administered for 8 weeks	Drug: Estradiol Tablets Oral estradiol 1 mg BID for 8 weeks Other Names: Oral Estradiol tablets
Active Comparator: Transdermal Estradiol Transdermal estradiol administered for 8 weeks	Drug: Transdermal patch Estradiol patch therapy for 8 weeks Other Names: Transdermal estradiol patch

Arm

Intervention/Treatment

Active Comparator: Sublingual Estradiol

Sublingual estradiol administered for 8 weeks

Drug: Estradiol Tablets

Oral estradiol will be taken sublingually, 1 mg BID for 8 weeks

Other Names:

Sublingual estradiol tablets

Active Comparator: Oral Estradiol

Oral estradiol administered for 8 weeks

Drug: Estradiol Tablets

Oral estradiol 1 mg BID for 8 weeks

Other Names:

Oral Estradiol tablets

Active Comparator: Transdermal Estradiol

Transdermal estradiol administered for 8 weeks

Drug: Transdermal patch

Estradiol patch therapy for 8 weeks

Other Names:

Transdermal estradiol patch

Outcome Measures

Primary Outcome Measures

Coagulation system activation and fibrinolysis due to estradiol administration [8 months]
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.

Secondary Outcome Measures

Thrombotic risk due to estradiol administration [8 months]
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).