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Luteinizing hormone–releasing hormone (LHRH) agonists are the most widely used agents to achieve medical castration. The original nonsurgical option was estrogen (in the form of diethylstilbestrol) but it was broadly abandoned secondary to association with an increase in thromboembolic events and the introduction of LHRH agonists. Transdermal administration of estradiol has the potential to avoid the first-pass hepatic metabolism associated with activation of coagulation pathways. In a phase 2/3 randomized trial, investigators compared cardiovascular outcomes with transdermal estrogen (TDE) patches versus LHRH agonists in men with locally advanced or metastatic prostate cancer.
Over a 12-year period the investigators enrolled 1694 men in the…