Transgender Estradiol

Early Phase 1

Completed

Conditions: Transgender Persons

Interventions: Drug: Estradiol

Registration Number: NCT04036500

Lead Sponsor: Medical College of Wisconsin

Brief Summary: Blogs, word-of-mouth, and small studies from the 1990s in the premature ovarian insufficiency and menopause populations have suggested sublingual or transdermal estradiol may be safer and/or more effective than an oral formulation. Sublingual administration entails holding the estrogen tablet under the tongue and allowing it to dissolve, where its absorption is enhanced by the rich vascularization under the tongue. According to Price et al., sublingual administration results in rapid absorption with significantly higher estradiol levels than does comparable oral dosing. This is likely because sublingual administration will bypass metabolism by the intestines and liver. The transdermal route, which also bypasses first-pass metabolism, is not associated with an increased venous thromboembolic risk nor a significant increase in plasma triglycerides or HDL-cholesterol levels. As such, transdermal estrogen is often preferred over oral formulations, although it is relatively expensive and not accessible to many transgender women. Conversely, sublingual administration of estrogen tablets is widely available and could be a cost-effective alternative to transdermal estrogen. However, there are no well-conducted studies that have evaluated the safety and efficacy of sublingual estrogen therapy in the transgender population. This pilot study will elucidate how estrogen levels in the blood change following sublingual versus oral administration of estradiol in transgender women. This data may be used later to design larger studies on safety and efficacy.

Additionally, analyzing a dosage method that patients themselves have tried independently and found effective is also important. This approach incorporates intelligence from the transgender community into our research, creating new knowledge that is supported by data but is founded in existing community insights. Thus, the outcomes of this research have the potential to integrate patient input while also aiding in the development of safety recommendations, with the goal of better caring for our transgender patients.

Primary aim. To establish the pharmacokinetics of sublingual estradiol versus oral estradiol in transgender women.

Detailed Description: Patient will plan on being in the Adult Translational Research Unit (A-TRU) for 8 hours. They will be assigned to a suite. They will get 7 blood draws at hours 0,1,2,3,4,6,8 and vitals at the beginning of the visit. Vitals will include height, weight, blood pressure, respiration rate, and pulse. Subject is able to eat while in the A-TRU. Day 1 patient will take estradiol 1 mg ORALLY after time 0 blood draw. The medication will be given by registered nurse. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. Subject cannot take any hormone replacement therapy between their research appointments. On day 2, subject will take estradiol 1 mg SUBLINGUALLY after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Transgender male-to-female
Naive to hormone therapy
English speaker
18 years of age or older

Exclusion Criteria

History of hormone replacement therapy
Orchiectomy
Needle phobia
Serious bleeding condition
Active deep vein thrombosis, pulmonary embolism or history of these conditions
Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction)
Liver dysfunction or disease
History of breast cancer
Known sensitivity or allergy to any components of the medications used
Taking potent CYP3A4 inhibitors or inducers, as determined by team pharmacist
Taking a medication that may cause additional physical or mental harm if stopped

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Estradiol 1 mg oral first, then Estradiol 1 mg sublingual	Estradiol	Subjects will take estradiol 1 mg orally after time 0 blood draw. They will get 7 blood draws at hours 0,1,2,3,4,6,8. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. On day 2 of study, subject will take estradiol 1 mg sublingually after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1 of study.

Primary Outcome Measures

Name	Time	Method
Maximum Serum Concentration of Estradiol	8 hours
Area Under the Serum Concentration Versus Time Curve	8 hours	Mean for Area Under the Curve(AUC) for sublingual estradiol.
Oral Clearance of Estradiol	8 hours

Secondary Outcome Measures