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Clinicians frequently prescribe sex hormone therapy for various conditions. However, hormone-associated venous thromboembolism remains a significant clinical concern. Consequently, practitioners must understand how these treatments influence hemostasis and cardiovascular health. This review examines current evidence regarding thrombotic risks across different hormone formulations. Furthermore, it provides guidance for perioperative care and risk mitigation.
Specifically, sex hormone therapy encompasses many indications. These include hormone replacement for deficiencies, contraception, and oncologic treatment. Additionally, gender-affirming hormone therapy (GAHT) and ovulation suppression require careful monitoring. Recent studies highlight that formulation choice significantly impacts risk profiles. For instance, combined oral contraceptives often pose a higher risk compared to progestin-only methods. Similarly, transdermal estrogens generally appear safer than oral preparations in postmenopausal women.
Moreover, patient-specific factors play a critical role in risk assessment. Underlying thrombophilias and a history of prior thrombosis increase the likelihood of new events. Therefore, clinicians should perform thorough screenings before initiating therapy. In addition, common clinical factors like obesity and smoking can exacerbate thrombotic tendencies. Therefore, individualizing treatment plans is essential for patient safety. Patients receiving GAHT also require nuanced care, as estrogen-based regimens may elevate VTE rates compared to cisgender peers. Consequently, transdermal options should be considered for high-risk individuals.
Furthermore, perioperative management demands specific attention. Surgeons often recommend pausing hormone therapy before major procedures. However, this decision must balance the risk of thrombosis with the clinical necessity of the treatment. For example, stopping gender-affirming therapy can lead to significant psychological distress. Thus, shared decision-making becomes vital. Finally, clinicians must stay updated on evolving guidelines to optimize patient outcomes.
Progestin-only methods, such as levonorgestrel intrauterine devices (IUDs), and transdermal estrogen preparations generally carry a lower risk of thrombosis compared to combined oral contraceptives and oral estrogens.
Estrogen-based gender-affirming therapy can increase the risk of venous thromboembolism, particularly with oral formulations. Clinicians should assess individual risk factors and consider transdermal routes for those at higher risk.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a substitute for professional healthcare. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
1. Skeith L et al. Sex Hormone Influences on Venous Thrombotic and Cardiovascular Risk. N Engl J Med. 2026 Apr 16. doi: 10.1056/NEJMra2202438. PMID: 41985134.
2. Yonis HGH, et al. Contemporary hormonal contraception and risk of venous thromboembolism. JAMA. 2025;333(6):521-530. doi:10.1001/jama.2024.28778.
3. Bouck EG, et al. Thromboembolic risk with gender-affirming hormone therapy: potential role of global coagulation and fibrinolysis assays. Endocrine Practice. 2023;29(10):812-822.

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