Minimizing venous thromboembolism in feminizing hormone therapy: applying lessons from cisgender women and previous data.

Abstract Estrogen is a known risk factor for venous thromboembolism (VTE), as documented in several large-scale studies of combined oral contraceptives (COC) and postmenopausal hormone replacement therapy (HT) for cisgender women. The impact of estrogen-containing feminizing hormone regimens on transgender individuals’ risk for VTE remains insufficiently understood due to a paucity of studies and extrapolation from cisgender women. We evaluated VTE risk by screening 1,170 relevant studies published from 1994-2020, focusing on meta-analysis data. The type of oral estrogen, route of administration, patient demographics, and comorbidities may affect the risk of VTE. Venous thrombosis is the most common vascular complication associated with HT. Conjugated equine estrogens (CEEs) and 17-beta estradiol appear to be safer than oral ethinyl estradiol. Transdermal estrogen formulations appear to be the least thrombogenic estrogens. Estrogens used concomitantly with progestins increase the risk of VTE compared to estrogens alone. To date, there are no data to demonstrate the benefit of holding HT prior to vaginoplasty or other gender-affirming surgeries. For most young, healthy transgender women, there is little risk of VTE with HT, while older patients with risk factors should be discussed case by case.