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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05428215

Enrollment

Registered

2022-06-23

Start date

2022-12-29

Completion date

2023-07-20

Last updated

2023-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gender Dysphoria

Keywords

estradiol, gender-affirming estrogen

Brief summary

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

Interventions

DRUG17beta Estradiol

Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Each subject will take their individualized dose of 17B-estradiol tablet orally for 2 weeks and sublingually for 2 weeks. The subject will then take their same dose of 17B-estradiol via the other means of administration for 2 weeks. The order in which this occurs will be randomized.

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Estradiol absorption	Over 24 hours	Mean area under the curve of estradiol

Secondary

Measure	Time frame	Description
Peak serum estradiol	Peak over 24 hour period	With subjects as own controls, compare peak E2 with sublingual vs oral administration
Serum estradiol Nadir	24 hours from last estradiol administration	Baseline serum estradiol level after 2 weeks of oral administration versus sublingual administration at same dose
Suppression of Testosterone	24 hours from last estradiol administration on Study Day 14 and 28	Testosterone level after 2 weeks of estradiol administration via oral and sublingual method, respectively
Serum estrone to estradiol ratio	Hours from administration of estradiol: 0, 1, 2, 4, 6, and 8 hours	E1:E2 ratio over 24 hour period with sublingual vs oral administration
Sex hormone binding globulin	0 hours from estradiol administration on Study Day 14 and 28	SHBG after 2 weeks of estradiol sublingual vs oral administration

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026