Transgender Estradiol

Transgender Persons Clinical Trial

Official title:

Sublingual Estradiol Versus Oral Estradiol in Transgender Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04036500
• Other study ID #: PRO00035015
• Status: Completed
• Phase: Early Phase 1
• Start date: September 23, 2019
• Est. completion date: July 13, 2020

Study information

• Verified date: August 2020
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 13, 2020
• Est. primary completion date: July 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Transgender Persons

Intervention

Drug:
• Estradiol Tablets
Patients will be given estradiol: 1 mg oral or 1 mg sublingual.

Locations

Country	Name	City	State
United States	Froedtert Hospital	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum serum concentration of estradiol		8 hours
Primary	Half-life of estradiol		8 hours
Primary	Area under the serum concentration versus time curve		8 hours
Primary	Oral clearance of estradiol		8 hours
Primary	Ratio of estrone to estradiol		8 hours