Hormones, cancer, and thrombosis: sex-specific mechanisms at the interface of hemostasis and vascular biology

This review examines the complex relationship between hormonal signaling, cancer biology, and thrombosis, focusing primarily on cancer-associated venous thromboembolism (VTE) in hormone-sensitive malignancies. Hormones regulate key hemostatic processes—including coagulation, platelet activity, endothelial function, and fibrinolysis—and disturbances in these pathways can promote thrombotic complications in patients with cancer. Sex hormones play distinct roles in modulating thrombotic risk. Estrogens tend to promote a prothrombotic state by increasing procoagulant factors and reducing anticoagulant activity, whereas progesterone has minimal direct hemostatic effects. The impact of testosterone remains less clear, although some data suggest a transient increase in VTE risk shortly after initiation of testosterone therapy. In hormone-dependent cancers, endocrine therapies further modify thrombotic risk through their effects on hormonal pathways and tumor-associated inflammation. The magnitude and mechanisms of thrombosis vary across malignancies. In breast cancer, VTE risk is generally moderate but increases with age, obesity, disease stage, chemotherapy, and particularly endocrine therapy such as tamoxifen, which is associated with a two- to three-fold higher VTE risk. Ovarian cancer is among the most thrombogenic solid tumors, driven by tumor biology, inflammatory activation, and intensive treatments such as surgery and platinum-based chemotherapy. Endometrial cancer risk is linked to prolonged estrogen exposure and obesity, while prostate cancer demonstrates increased thrombotic risk primarily related to androgen deprivation therapy, which induces metabolic and vascular changes that favor hypercoagulability. These sex-specific differences highlight the need for risk-adapted strategies for thromboprophylaxis and surveillance. Clinical management should consider tumor type, hormonal environment, treatment modality, and patient-specific risk factors. As survival improves in hormone-sensitive cancers, optimizing prevention of thrombotic complications while minimizing bleeding risk represents an important component of personalized oncologic care.