Transgender Estradiol

NCT04036500 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: PRO00035015
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Transgender Persons

Outcome Measures

Primary Outcomes (3)

• Maximum Serum Concentration of Estradiol

  8 hours

• Area Under the Serum Concentration Versus Time Curve

  Mean for Area Under the Curve(AUC) for sublingual estradiol.

  8 hours

• Oral Clearance of Estradiol

  8 hours

Secondary Outcomes (1)

• Ratio of Estrone to Estradiol

  8 hours

Study Arms (1)

Estradiol 1 mg oral first, then Estradiol 1 mg sublingual

EXPERIMENTAL

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

Interventions

Estradiol DRUG

Patients will be given estradiol: 1 mg oral and 1 mg sublingual.

Estradiol 1 mg oral first, then Estradiol 1 mg sublingual

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Transgender male to female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Jenna Sarvaideo, DO
• Organization: Medical College of Wisconsin

jsarvaideo@mcw.edu

414-955-7069

Study Officials

• Jenna L Investigator, DO

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 29, 2019
• Study Start: September 23, 2019
• Primary Completion: July 13, 2020
• Study Completion: July 13, 2020
• Last Updated: April 11, 2025
• Results First Posted: April 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: starting 3 months after publication
• Access Criteria: IPD will be shared if PI is directly contacted and asked for the above information.

Locations

US (1)