Hormonal therapies and venous thrombosis: Considerations for prevention and management

Abstract

Background: Venous thromboses are well-established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks.

Objectives: To review and discuss the differences in thrombosis risk of the many of hormonal preparations available as well as their interaction with patient-specific factors.

Methods: We conducted a narrative review of the available literature regarding venous thrombosis and hormonal therapies including for contraception, menopausal symptoms, and gender transition.

Results: Thrombosis risk with estrogen-containing compounds increases with increasing systemic dose of estrogen. While progesterone-only-containing products are not associated with thrombosis, when paired with estrogen in combined oral contraceptives, the formulation of progesterone does impact the risk. These components, along with patient-specific factors, may influence the choice of hormonal preparation. For patients who develop thrombosis on hormonal treatment, anticoagulation is protective against future thrombosis. Duration of anticoagulation is dependent on ongoing and future hormone therapy choice. Finally, the optimal management of hormone therapy for individuals diagnosed with prothrombotic illnesses such as COVID-19 remains unclear.

Conclusions: When contemplating hormonal contraception or hormone replacement therapy, clinicians must consider a variety of factors including hormone type, dose, route, personal and family history of thrombosis, and other prothrombotic risk factors to make informed, personalized decisions regarding the risk of venous thrombosis.

Keywords: estrogens; hormonal contraception; hormone replacement therapy; thrombosis, transgender people.

FIGURE 1

List of available hormone preparations for contraception in the United States. Formulations are grouped roughly in order of ascending risk of VTE based on the best available evidence. Note the individual exceptions in each of the different generations of COC. *Effectiveness as measured by prevention of unwanted pregnancy in the first year of typical use (Reference [33]) †Contraindicated in those with prior DVT, though this is based on data regarding oral preparations of etonogestrel ‡Reference [30] §Reference [34] ¶ Contraindicated in body mass index ≥30 kg/m² **Reference [20] ††Not available in the United States for contraception but is included in this table for completion's sake ‡‡ All formulations with ethinyl estradiol dose of >50 μg are labeled as high risk of VTE. Abbreviations: COC, combined oral contraception; LNG IUD, levonorgestrel intrauterine device; OR, odds ratio; VTE, venous thromboembolism

FIGURE 2

Proposed flowcharts for the consideration of initiating hormonal contraceptive therapy or hormone replacement therapy (A), and for the approach to the patient who develops a venous thromboembolic event while on the aforementioned therapy (B). *Risk factor for consideration but should undergo risk/benefit discussion with the patient †Expert advice may be needed to determine factors. Abbreviations: BMI, body mass index; COC, combined oral contraceptive; HRT, hormone replacement therapy; LNG IUD, levonorgestrel intrauterine device; VTE, venous thromboembolism