Clinical trial NCT05387577: Coagulation and Fibrinolysis of Estradiol in Transwomen
Official title: Coagulation Activation and Fibrinolysis With Sublingual Versus Oral Versus Transdermal Estradiol in Transgender Women
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Transgenderism
Clotting Disorder
Keywords: Estradiol
Estrogens
Hormones
Hormones, Hormone Substitutes, Hormone Antagonists
Physiological Effects of Drugs
Transgender
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Coagulation system activation and fibrinolysis due to estradiol administration
timeFrame: 8 months
Secondary outcomes:
measure: Thrombotic risk due to estradiol administration
timeFrame: 8 months
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Jenna Sarvaideo, DO
role: PRINCIPAL_INVESTIGATOR
References: