Comparison of PKs of 17-Beta-Estradiol Via Sublingual Placement Versus Swallowing in Male-to-Female Transgender Patients

Study Overview
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Brief Summary
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This crossover study will investigate the pharmacokinetics of oral versus sublingual administration of 17-beta-estradiol in the trans-female population.

Official Title
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Comparison of Pharmacokinetics of 17-Beta-Estradiol Via Oral Administration With Sublingual Placement Versus Oral Administration With Swallowing of 17-Beta-estradiol in Male-to-Female Transgender Patients

Conditions
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Gender Dysphoria

Intervention / Treatment
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* Drug: 17beta Estradiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaker Currently taking 17-beta-estradiol tablet daily via sublingual or oral route on dose therapeutic for gender-affirming therapy; steady dose for at least 4 weeks Serum estradiol and testosterone levels within target therapeutic range (75-200 pg/mL and <55 ng/dL, respectively) Exclusion Criteria: Active or history of deep venous thrombosis/pulmonary embolism Active or recent (within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction) Liver dysfunction History of breast cancer History of orchiectomy Known sensitivity or allergy to any components of the study medication Taking potent CYP3A4 inhibitors or inducers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each subject will take their individualized dose of 17B-estradiol tablet orally for 2 weeks and sublingually for 2 weeks. The subject will then take their same dose of 17B-estradiol via the other means of administration for 2 weeks. The order in which this occurs will be randomized.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PO then SL<br>Subjects will administer 17-beta-estradiol orally (PO) for Study Day 1-14, followed by administration of 17-beta-estradiol sublingually (SL) for Study Day 15-28. | Drug: 17beta Estradiol<br>* Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration<br>|
| Active Comparator: SL then PO<br>Subjects will administer 17-beta-estradiol sublingually (SL) for Study Day 1-14, followed by administration of 17-beta-estradiol orally (PO) for Study Day 15-28. | Drug: 17beta Estradiol<br>* Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estradiol absorption | Mean area under the curve of estradiol | Over 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak serum estradiol | With subjects as own controls, compare peak E2 with sublingual vs oral administration | Peak over 24 hour period | 
| Serum estradiol Nadir | Baseline serum estradiol level after 2 weeks of oral administration versus sublingual administration at same dose | 24 hours from last estradiol administration | 
| Suppression of Testosterone | Testosterone level after 2 weeks of estradiol administration via oral and sublingual method, respectively | 24 hours from last estradiol administration on Study Day 14 and 28 | 
| Serum estrone to estradiol ratio | E1:E2 ratio over 24 hour period with sublingual vs oral administration | Hours from administration of estradiol: 0, 1, 2, 4, 6, and 8 hours | 
| Sex hormone binding globulin | SHBG after 2 weeks of estradiol sublingual vs oral administration | 0 hours from estradiol administration on Study Day 14 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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estradiol, gender-affirming estrogen