Transgender Estradiol

Sublingual Estradiol Versus Oral Estradiol in Transgender Women

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.

Study Overview

• Status: Completed
• Conditions: Transgender Persons
• Intervention / Treatment: Drug: Estradiol Tablets

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum serum concentration of estradiol	8 hours
Half-life of estradiol	8 hours
Area under the serum concentration versus time curve	8 hours
Oral clearance of estradiol	8 hours
Ratio of estrone to estradiol	8 hours

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Jenna L Investigator, DO, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): July 13, 2020
• Study Completion (Actual): July 13, 2020

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: PRO00035015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All individual participant data that underlie results in a publication.
• IPD Sharing Time Frame: starting 3 months after publication
• IPD Sharing Access Criteria: IPD will be shared if PI is directly contacted and asked for the above information.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No