Gender Dysphoria, Adult, Blood Coagulation, Coagulation Factors, Transgender Persons, M01.777.500, Hemostasis, Transgender Women
Conditions
Keywords
Transgender women, sublingual estradiol, procoagulant effect, Protein S, Thrombin generation assay (TGA), Gender-affirming hormone therapy (GAHT)
Brief summary
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
Interventions
DRUGEstradiol (E2)
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.
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.
Sponsors
Tel-Aviv Sourasky Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Plasma Free Protein S Antigen Concentration at 6 Months | Baseline and 6 months after initiation of therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Prothrombin Time (PT) from baseline to 6 months | Baseline and 6 months after initiation of therapy | PT will be measured at baseline and after 6 months using conventional clotting assays to evaluate changes in coagulation function. |
| Change from Baseline in Partial Thromboplastin Time (PTT) at 6 Months | Baseline and 6 months after initiation of therapy | PTT will be measured at baseline and after 6 months using conventional clotting assays to evaluate changes in intrinsic coagulation pathway function |
| Change from Baseline in International Normalized Ratio (INR) at 6 Months | Baseline and 6 months after initiation of therapy | INR will be measured at baseline and after 6 months using standard prothrombin time-based assays to assess changes in coagulation status. |
| Change from Baseline in Thromboelastography (TEG) Reaction Time (R Time) at 6 Months | Baseline and 6 months after initiation of therapy | TEG Reaction Time (R time) will be measured at baseline and after 6 months using thromboelastography. R time is defined as the latency period from the start of the test until initial fibrin formation begins, reflecting the initiation phase of coagulation. |
| Change in Protein C from baseline to 6 months | Baseline and 6 months after initiation of therapy | Plasma concentration of Protein C antigen will be measured using immunologic assays at baseline and after 6 months of treatment. |
| Change from Baseline in Thrombin Generation Assay (TGA) Lag Time at 6 Months | Baseline and 6 months after initiation of therapy | Lag time in the thrombin generation assay will be measured at baseline and after 6 months. TGA lag time represents the time until the initiation of thrombin generation, reflecting the onset of the coagulation process. |
| Change from Baseline in Thrombin Generation Assay (TGA) Peak Thrombin at 6 Months | Baseline and 6 months after initiation of therapy | Peak thrombin levels will be measured using thrombin generation assay at baseline and after 6 months. This metric represents the highest concentration of thrombin generated during the assay and reflects the overall procoagulant potential. |
| Change from Baseline in Thrombin Generation Assay (TGA) Area Under the Curve (AUC) at 6 Months | Baseline and 6 months after initiation of therapy | The area under the curve (AUC) in the thrombin generation assay will be calculated at baseline and after 6 months. AUC reflects the total amount of thrombin generated over time, providing a global measure of thrombin-generating capacity. |
| Change from Baseline in Thromboelastography (TEG) Maximum Amplitude (MA) at 6 Months | Baseline and 6 months after initiation of therapy | TEG Maximum Amplitude (MA) will be measured at baseline and after 6 months using thromboelastography. MA reflects the maximum strength of the formed clot and is influenced by platelet function and fibrinogen levels. |
Countries
Israel
Outcome results
None listed