One of the most serious side effects of feminizing hormone therapy can be the development of thrombosis, a blood clot which blocks the normal circulation of blood, leading to potentially fatal conditions such as pulmonary embolism, heart attack, or stroke. While this has been a known risk since the initial development of HRT, the nature and extent of that risk has been a matter of lengthy debate. Prior to the adoption of bioidentical estradiol in trans women’s HRT regimens, conjugated equine estrogens or the synthetic estrogen ethinylestradiol were typically used, and ethinylestradiol is associated with an elevated likelihood of developing blood clots; route of administration may also be a factor, and injectable or transdermal estradiol may carry less thrombotic risk than oral estradiol. However, even including earlier studies in which synthetic estrogens were used, a meta-analysis by Khan et al. (2019) found that the risk of thrombosis among trans women on HRT was not higher than the risk among cis women taking oral contraception. And thrombosis is not considered to be a risk associated with testosterone treatment as part of masculinizing HRT (Hembree et al., 2017), although a case has been reported in a 17-year-old trans boy who was taking both testosterone as well as an ethinylestradiol-containing oral contraceptive (Stanley & Cooper, 2018).
Khatchadourian, Amed, & Metzger (2014) found that among 63 trans girls and boys receiving cross-sex hormone therapy in adolescence, no cases of serious side effects such as thrombosis were reported. A recent abstract of a study by Kowalczyk Mullins et al. (2020) at the Cincinnati Children’s Hospital Medical Center reports the frequency of thrombosis observed among 635 trans adolescents and young adults aged 13-24 receiving estrogen or testosterone treatment. How many experienced thrombosis during this treatment? Zero.
None of the 635 patients developed clinically significant thrombosis. One patient experienced recurrent superficial thrombophlebitis associated with peripheral intravenous catheters.
Three patients had a history of previous thrombosis and two were on prophylactic anti-clotting treatment; another three were started on anti-clotting treatment upon initiating HRT due to risk factors for thrombosis. Nonetheless, neither these patients nor any others experienced thrombosis during cross-sex hormone therapy. The authors recommend:
Clinicians should 1) obtain a careful and detailed personal and family history of risk factors for and history of thrombosis and consider referral to a hematologist to discuss the risks associated with GAHT, and 2) counsel about modifiable risk factors such as tobacco use and obesity.
At a time when multiple state legislatures are moving to prohibit the administration of puberty blockers and cross-sex hormones to trans adolescents, studies such as these are essential to establishing the basic safety of these treatments. Medical transition in adolescence is beneficial to trans youth, necessary for their well-being, and, as this latest study indicates, low-risk and safe. ■
