Comparing the Effects of Sublingual Estradiol Treatment Versus Oral Estradiol With Cyproterone Acetate (CPA) Treatment on The Coagulation System in Transgender Women: A Prospective, Controlled Cohort Study

Tel-Aviv Sourasky Medical Center30 enrolled

Overview

The goal of this clinical trial is to learn about the effects of different routes of estradiol administration on blood clotting in transgender women starting gender-affirming hormone therapy. The main questions it aims to answer are: Does sublingual estradiol reduce free Protein S levels compared to oral estradiol with cyproterone acetate? Does sublingual estradiol accelerate activation of the clotting system, as measured by thrombin generation? Researchers will compare sublingual estradiol to oral estradiol plus cyproterone acetate to see if the way estradiol is taken changes blood clotting risk. Participants will: Take either sublingual estradiol (2 mg daily in divided doses) or oral estradiol (2 mg daily) with cyproterone acetate (10 mg daily) for 6 months Provide blood samples at baseline and after 6 months to measure hormone levels and clotting factors Attend clinic visits for monitoring, including safety checks and routine laboratory tests

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Gender Dysphoria, Adult Blood Coagulation Coagulation Factors

Interventions

Estradiol (E2)DRUG

Participants receive estradiol 2 mg/day. In the experimental arm, estradiol is administered sublingually in four divided doses (0.5 mg each). In the active comparator arm, estradiol is administered orally, in combination with cyproterone acetate, for 6 months. All participants are treatment-naive.

Cyproterone Acetate (Androcur, BAY94-8367)DRUG

Participants in the active comparator arm receive cyproterone acetate (CPA) 10 mg orally, once daily, in combination with oral estradiol, for 6 months. All participants are treatment-naive.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Self-identified transgender women * Aged 18 to 45 years * Healthy individuals * Treatment-naïve (not previously exposed to gender-affirming hormone therapy) * Presenting for gender-affirming hormone therapy (GAHT) * Provided written informed consent Exclusion Criteria: * Active smokers * Personal or family history of venous thromboembolism (VTE) or thrombophilia * History of malignancy in the past 5 years * Chronic liver disease * Chronic kidney disease * Hyperlipidemia

Outcomes

Primary Outcomes

Change from Baseline in Plasma Free Protein S Antigen Concentration at 6 Months

Plasma concentration of free Protein S antigen will be measured at baseline and after 6 months of treatment. A reduction of ≥20% in free Protein S is anticipated in the sublingual estradiol group, with no comparable change expected in the oral estradiol group.