<p>Managing the risk of venous thromboembolism in transgender adults undergoing hormone therapy</p>

Abstract

Introduction: Venous thromboembolism (VTE) is a potential risk of estrogen therapy. However, data show an improvement in the quality of life for transgender people who use feminizing hormone therapy. With few transgender-specific data, guidance may be drawn from cisgender (nontransgender) data, with a focus on hormonal birth control and postmenopausal hormone replacement therapy (HRT). The aim of this review is to examine the degree to which routes of administration, patient comorbidities, and type of hormone utilized affect the safety of estrogen therapy. Methods: We identified 6,349 studies by searching PubMed with the terms “transgender”, “estrogen”, “VTE”, and “HRT”. Of these, there were only 13 studies between 1989 and 2018 that investigated the effects of hormone therapy, including types of estrogens used, in transgender women and men. Results: The data suggest that the route of hormone administration, patient demographics, and patient comorbidities all affect estrogen’s link with VTE. For example, avoiding ethinyl estradiol might make the use of hormone therapy in trans feminine individuals safer than oral birth control. Data from both cis and trans groups suggest additional VTE risk associated with the use of progestins. While transdermal estrogens dosed up to 0.1 mg/day or below appear lower risk for VTE than other forms of estrogen, it is unclear whether this is related to the delivery method or a dose effect. Finally, even if the risk from exogenous estrogen use remains significant statistically, the absolute clinical risk remains low. Conclusion: Clinicians should avoid the use of ethinyl estradiol. Additionally, data suggest that progestins should be avoided for transgender individuals. Further study of the relationship between estrogen use and the risk of VTE will serve to inform the safest care strategies for transgender individuals.

Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger?

“…Noteworthy, in women, conditions of exposure to su­praphysiological estrogen levels, such as during the use of estrogen-containing oral contraceptives, or extremely high estrogen levels, such as in pregnancy, represent two exceptions, given that these conditions increase the procoagulant factors FVII, FIX, FX, FXII, and FXIII levels and decrease the anticoagulant factors protein S and antithrombin levels, thus altering the hemostatic balance towards a prothrombotic state [ 82 , 83 ]. Interestingly, in transgender women the use of estrogens is independently associated with a 3-fold increase in cardiovascular mortality, as it is known to induce an increase in body and visceral fat as well as weight and triglycerides, to reduce lean mass, and to promote prothrombotic state [ 84 , 85 ]. In transgender men the use of androgens does not increase cardiovascular mortality despite its negative impact not only on hematocrit but also on lipid profile [ 84 , 85 ].…”

“…Interestingly, in transgender women the use of estrogens is independently associated with a 3-fold increase in cardiovascular mortality, as it is known to induce an increase in body and visceral fat as well as weight and triglycerides, to reduce lean mass, and to promote prothrombotic state [ 84 , 85 ]. In transgender men the use of androgens does not increase cardiovascular mortality despite its negative impact not only on hematocrit but also on lipid profile [ 84 , 85 ]. Notably, in men the condition of testosterone deficiency, such as in hypogonadism, is associated with an increase in procoagulant factors, including FV, FX, and C-reactive protein, and a decrease in anticoagulant factors, such as antithrombin III [ 86 ]; this evidence suggests that the condition of androgen deficiency further worsens the susceptibility of men for thrombosis, explaining the exaggerated increase in incidence of thrombosis in old compared to young men.…”

An Observational Study of Hypertension and Thromboembolism Among Transgender Patients Using Gender-Affirming Hormone Therapy

“…13 However, it is thought that transdermal and parenteral routes of administration have less of a thromboembolic risk since they avoid the first pass effect. [14][15][16] For masculinizing therapy, testosterone is used as HT in trans men (TM), in various formulations such as parenteral, topical, or transdermal; patients may also use topical estrogens to counteract vaginal atrophy.…”

Characteristics of Transgender Women Referred to Women's Heart Clinic

“… [22] There is data in both transgender and cisgender women to suggest some degree of increased rate of venous thromboembolism on feminizing hormone therapy. [ 23 , 24 ] Of particular importance to our cohort, risk of thrombosis may increase over time. Providers should be particularly mindful of this when treating older TGD, as age confers additional risk for thrombosis on top of decades of estrogen administration.…”

“… [25] While head-to-head dose-equivalent trials are not available, the transdermal route is generally favored for its safety profile and is our current practice, especially in women at increased risk. [ 23 , 26 ]…”