Venous thromboembolism in the hormonal milieu

Hormonal therapy is administered for multiple indications including contraception, alleviation of menopausal symptoms, hypogonadism, and more recently, gender-affirming care. Data suggest varying degrees of increased risk for venous thromboembolism (VTE).

While oral progestin only methods do not appear to increase the risk of VTE, an association was seen with injection progestin contraception. Combined oral contraception with low-dose ethinyl estradiol and most types of progestin increased the risk of VTE compared with levonorgestrel-containing oral therapies. While transdermal hormonal contraception has been previously associated with increased VTE, a recently approved levonorgestrel and ethinyl estradiol transdermal patch reported low rates (<0.2%) in a large single-arm open-label study. Women receiving postmenopausal HRT experienced an increased risk of VTE in a dose-dependent manner when using oral hormonal therapy while nonoral methods, such as topical estrogen, did not appear to increase the risk of VTE. Some studies suggest no increased risk of VTE with testosterone therapy, however, a recent case-crossover study suggested higher VTE risk in men on testosterone, particularly men less than age 65 without hypogonadism. Route of administration had no effect on VTE rates. The estimated incidence rate of VTE risk in transgender women receiving estrogen therapy is 2.3 per 1000 person years, but may be imprecise due to heterogeneity in studies included in published meta-analyses. Surgical risk estimates are primarily indirect data drawn from cisgender patients receiving hormone therapy in the perioperative setting.

Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery.