Background: Transgender women have an increased risk of cardiovascular disease (CVD) compared with cisgender women and men. Platelet activation is an essential part of hemostasis and plays a role in CVD development. This might be influenced by female sex hormones, since platelets express estrogen receptors on their surface. To gain insight into the role of platelet activation in CVD development in trans women, we investigated the effect of estradiol on two markers of platelet activation: CD62p and CD63.

Methods: In this prospective cohort study, hormone-naïve trans women without platelet disorders were included. Intervention consisted of estradiol and anti-androgens. Blood was drawn at baseline and at week 2, 12 and 52. CD62p and CD63 were measured using flow cytometry. Based on the percentage of marker-positive platelets and median fluorescence intensity of these markers, a binding index (BI) was calculated. BI of CD62p and CD63 were log transformed before further analyses. Geometric means were calculated and linear mixed models were used to analyze the percentage changes in BI over time.

Results: Seventeen trans women (19-48 years) were included. For CD62p, BI increased from 2.4 (95%CI 1.5, 3.7) at baseline to 4.6 (95%CI 2.0, 10.5) at week 2, reflecting a difference of 96% (95%CI -9, 318). After week 2, BI decreased to 2.6 (95%CI 1.3, 5.3) at week 12 and 1.4 (95%CI 1.0, 1.9) at week 52. The difference between week 52 compared to baseline was -40% (95%CI -69, 14). CD63 BI increased from 10.7 (95%CI 7.1, 16.1) at baseline with 32% (95%CI -32, 158) to 14.1 (95%CI 8.8, 22.8) at week 2. At week 12 and 52, BI was 13.1 (95%CI 7.4, 23.2) and 9.3 (95%CI 5.9, 14.6), respectively. The difference between week 52 compared to week 0 was -13% (95%CI -51, 53).

Conclusion: The observed trends show an increase in binding index of both platelet activation markers directly after hormone therapy initiation. This could partially explain the increased rates of CVD in transgender women in the early stages of their hormone therapy, however it may not explain the long term CVD risk.