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

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

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

Study Overview

• Status: Terminated
• Conditions: Gender Dysphoria
• Intervention / Treatment: Drug: 17beta Estradiol

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Katherin Davis, MD; Phone Number: 336-909-5673; Email: katherine.davis@mainehealth.org
• Study Contact Backup: Name: Daniel Spratt, MD; Phone Number: 207-771-5549; Email: daniel.spratt@mainehealth.org

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PO then SL; 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; Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration
Active Comparator: SL then PO; 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; Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MaineHealth
• Investigators: Principal Investigator: Katherine Davis, MD, MaineHealth

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: estradiol; gender-affirming estrogen
• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Gender Dysphoria; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 1737257

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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