Hormonal therapies and venous thrombosis: Considerations for prevention and management Original paper

What was studied?

This study reviews the risk of venous thrombosis associated with various hormonal therapies, including those used for contraception, hormone replacement therapy (HRT), and gender transition. It explores the thrombogenic effects of estrogen-containing therapies and how different estrogen doses and formulations (such as oral, transdermal, and injectable) influence the likelihood of developing venous thromboembolism (VTE). The paper also discusses the impact of progestins when used in combination with estrogen, highlighting how various types of progestins, particularly third-generation progestins, contribute to thrombotic risk. In addition, the study considers patient-specific factors such as age, obesity, and genetic predispositions (e.g., Factor V Leiden mutation), which may modify the risk of thrombosis during hormonal therapy use.

Who was studied?

The review focuses on a broad group of individuals, including women using hormonal contraception, postmenopausal women on HRT, and transgender women undergoing gender-affirming hormone therapy. The study emphasizes the use of combined oral contraceptives (COCs), hormonal replacement therapies (both systemic and transdermal), and progestin-only contraceptives. It also covers the gender transition population, with particular attention to transgender women receiving estrogen therapy and the associated thrombotic risks. The study identifies individual risk factors such as age, family history of thrombosis, and the presence of inherited thrombophilias that increase susceptibility to thrombotic events when using hormonal therapies.

Most important findings

The study highlights key findings regarding venous thrombosis risk in users of hormonal therapies. It reveals that the risk of thrombosis increases with higher estrogen doses. For example, ethinyl estradiol (EE) in combined oral contraceptives has a significantly higher thrombosis risk compared to lower-dose formulations like estradiol valerate (E2V), which was shown to reduce VTE risk. Third-generation progestins (e.g., desogestrel and gestodene) are associated with an increased thrombosis risk compared to second-generation progestins like levonorgestrel. Transdermal estrogen has been found to carry a lower thrombosis risk than oral estrogen, likely due to its bypass of the liver and reduced effect on coagulation factors. Progestin-only contraceptives, such as the levonorgestrel intrauterine device (IUD), have no increased thrombosis risk, making them a safer option for women with a history of thrombosis or high thrombotic risk. The review also points to a higher risk of thrombosis in individuals with pre-existing conditions such as obesity and genetic thrombophilias, including Factor V Leiden.

Key implications

The primary implication of the study is that clinicians must carefully tailor hormonal therapy based on individual risk profiles, particularly for patients with a history of thrombosis or those at increased risk. The use of transdermal estrogen is recommended over oral estrogen for individuals at high risk of thrombosis, especially those with cardiovascular or coagulation disorders. For patients using combined oral contraceptives, the type of progestin should be considered, as third-generation progestins are associated with a higher risk of VTE. In transgender women, the use of oral estrogen should be approached with caution, especially in those with additional thrombophilic risk factors, and transdermal estrogen may be preferred. Progestin-only contraceptives and IUDs offer lower thrombosis risk and are optimal for women with a history of thrombosis or thrombophilia. The review also underscores the importance of patient counseling and shared decision-making when choosing hormonal therapies, taking into account factors such as age, body mass index (BMI), and genetic risks.