Gender-affirming hormone therapy may increase VTE risk among transgender women
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Gender‐affirming hormone therapy appeared to increase overall procoagulant profiles among transgender women but not transgender men, according to study results published in Journal of Thrombosis and Haemostasis.
The use of estradiol and antiandrogen therapies among transgender women may contribute to the increased risk for VTE observed in previous research, researchers noted.
“Several studies have reported an increased incidence of thrombotic — mainly VTE but also arterial thrombotic — events in transwomen using gender‐affirming hormone therapy,” Luuk J. J. Scheres, MD, researcher in the department of clinical epidemiology at Leiden University Medical Center in the Netherlands, told Healio. “For transmen using hormone therapy, few data are available and this risk is uncertain. The increased risk in transwomen suggests procoagulant changes of gender‐affirming hormone therapy in line with studies of women using hormonal contraceptives or therapy. However, the effects of gender‐affirming hormone therapy on coagulation are largely unknown.”
For this reason, Scheres and colleagues assessed the effect of gender‐affirming hormone therapy on coagulation parameters associated with VTE among 98 transgender women (mean age, 33.7 years; mean BMI, 24 kg/m2; 26.5% current smokers; 49% alcohol users) and 100 transgender men (mean age, 26.9 years; mean BMI, 25.5 kg/m2; 37% smokers; 49% alcohol users).
Nearly half (47%) of transwomen received 100 mg twice-weekly transdermal estradiol and 48% received 2 mg twice-daily oral estradiol valerate. Ninety-one also received the oral antiandrogen cyproterone acetate. Among transgender men, 59% received 250 mg intramuscular testosterone once every 2 weeks and 41% received 50 mg once-daily transdermal testosterone.
No thrombotic events occurred during the 1-year follow-up.
After 1 year of hormone therapy use among transgender women, researchers observed substantial procoagulant changes, with a mean increase in factor IX of 9.6 IU/dL (95% CI, 3.1-16) and in factor XI of 13.5 IU/dL (95% CI, 9.5-17.5). Protein C decreased on average by 7.7 IU/dL (95% CI, 10.1 to 5.2) and fibrinogen increased by 0.1 g/L (95% CI, 0.04 to 0.24).
Route of therapy administration appeared to influence changes in coagulation measures. Researchers observed mean increases of 0.22 g/L (95% CI, 0.06 to 0.51) in fibrinogen levels and 6.5 IU/dL (95% CI, 0.3-12.8) in free protein S levels and a mean decrease of 11.6 IU/dL (95% CI, 24.4 to 1.2) in factor IX among transgender women receiving oral vs. transdermal estradiol.
Conversely, researchers did not find substantial overall changes in procoagulant profiles among transgender men. They observed a mean increase in factor IX of 7.9 IU/dL (95% CI, 2.2-13.6) and an increase in hematocrit of 0.06 L/L (95% CI, 0.05-0.07). Although fibrinogen and protein C levels did not appear significantly altered, protein S increased on an average by 7.6 IU/dL (95% CI, 1.6-13.6). Mean differences in fibrinogen (0.27 g/L; 95% CI, 0.65 to 0.1) and protein C levels (7.7 IU/dL; 95% CI, 15.2 to 0.2) were lower among transgender men receiving intramuscular vs. transdermal testosterone.
“The start of gender‐affirming hormone therapy in transmen was not associated with apparent procoagulant changes; thus, these findings appear reassuring regarding the risk for VTE in transmen using testosterone, although no definite conclusions can be drawn based on this study,” Scheres said.
Future studies should evaluate the role of gender‐affirming hormone therapy on coagulation profiles and determine which changes are key in the observed risk for thrombotic events, he added.
“In addition, to draw definite conclusions on risk for VTE among transwomen and transmen, adequately sized robust cohort studies with appropriate control groups — cismen for transwomen and ciswomen for transmen — are needed,” Scheres said. “Ideally, as a next step, risk-assessment models are then developed to inform transpersons and their physicians on the absolute risk for VTE with use of different types of hormone therapy and will consequently aid informed decision-making.”
For more information:
Luuk J. J. Scheres, MD, can be reached at Leiden University Medical Center, Rapenburg 70, 2311 EZ Leiden, Netherlands; email: luuk.scheres@radboudumc.nl.
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