Thromboembolic Risk Associated with Hormone Therapy in Women: A Systematic Review.

Abstract

INTRODUCTION: Hormone therapy (HT), used for contraception, menopause management, and gender transition, has been associated with increased risk of venous thromboembolism (VTE) and pulmonary embolism (PE). OBJECTIVES: To systematically review the evidence on thromboembolic risks associated with HT and identify modifying factors. METHODS: A systematic review following PRISMA guidelines was conducted, with searches in PubMed, Cochrane Library, and BVS (2015–2025), based on PICO criteria. Thirty-five studies (clinical trials, cohort, and case-control) were included. RESULTS AND DISCUSSION: Thromboembolic risk varied according to hormone type, administration route, dosage, and individual characteristics. Combined oral contraceptives with third- and fourth-generation progestins and higher estrogen doses were linked to increased risk, while levonorgestrel-based formulations and transdermal administration showed safer profiles. In postmenopausal women, conjugated equine estrogens and synthetic progestins raised risk, whereas 17β-estradiol and micronized progesterone showed lower thrombotic potential. In transgender women, oral ethinylestradiol was strongly associated with higher risk, supporting recommendations for 17β-estradiol via nonoral routes. FINAL CONSIDERATION: HT increases the risk of VTE/PE, but the magnitude is variable and context-dependent. Individualized assessment, risk factor screening, continuous monitoring, and safer hormone choices are essential for clinical safety. 

Keywords: Contraceptives; Thrombotic risk; Hormone therapy; Venous thromboembolism; Hormone replacement therapy.