Coagulation and Fibrinolysis of Estradiol in Transwomen

Medical College of Wisconsin

Status and phase: Terminated; Early Phase 1

Conditions: Clotting Disorder; Transgenderism

Treatments: Drug: Transdermal patch; Drug: Estradiol Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT05387577

PRO00036346

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: Male

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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6 participants in 3 patient groups

Sublingual Estradiol

Active Comparator group

Description:

Sublingual estradiol administered for 8 weeks

Treatment:

Drug: Estradiol Tablets

Drug: Estradiol Tablets

Oral Estradiol

Active Comparator group

Description:

Oral estradiol administered for 8 weeks

Treatment:

Drug: Estradiol Tablets

Drug: Estradiol Tablets

Transdermal Estradiol

Active Comparator group

Description:

Transdermal estradiol administered for 8 weeks

Treatment:

Drug: Transdermal patch