reported in men treated with EMP. These side effects are due to high estrogen levels and low testosterone levels. Prophylactic irradiation of the breasts can be used to decrease the incidence and severity of gynecomastia with estrogens. Severe adverse effects of EMP are thromboembolic and cardiovascular complications including pulmonary embolism, deep vein thrombosis, stroke, thrombophlebitis, coronary artery disease (ischemic heart disease; e.g., myocardial infarction), thrombophlebitis, and congestive heart failure with fluid retention. EMP produces cardiovascular toxicity similarly to diethylstilbestrol, but to a lesser extent in comparison at low doses (e.g., 280 mg/day oral EMP vs. 1 mg/day oral diethylstilbestrol). The prostate cancer disease state also increases the risk of thromboembolism, and combination with docetaxel may exacerbate the risk of thromboembolism as well. Meta-analyses of clinical trials have found that the overall risk of thromboembolism with EMP is 4 to 7%, relative to 0.4% for chemotherapy regimens without EMP. Thromboembolism is the major toxicity-related cause of discontinuation of EMP. Anticoagulant therapy with medications such as aspirin, warfarin, unfractionated and low-molecular-weight heparin, and vitamin K antagonists can be useful for decreasing the risk of thromboembolism with EMP and other estrogens like diethylstilbestrol and ethinylestradiol. Adverse liver function tests are commonly seen with EMP, but severe liver dysfunction is rare with the medication. Central nervous system side effects are rarely seen with EMP, although enlarged ventricles and neuronal pigmentation have been reported in monkeys treated with very high doses of EMP (20–140 mg/kg/day) for 3 to 6 months. EMP does not appear to have cytostatic effects in normal brain tissue. In women treated with EMP in clinical studies, a few instances of minor gynecological hemorrhages have been observed. EMP is described as relatively well tolerated among cytostatic antineoplastic and nitrogen-mustard agents, rarely or not at all being associated with significant hematologic toxicity such as myelosuppression (bone marrow suppression), gastrointestinal toxicity, or other more marked toxicity associated with such agents. In contrast to most other cytostatic agents, which often cause myelosuppression, leukopenia (decreased white blood cell count), and neutropenia (decreased neutrophil count), EMP actually produces leukocytosis (increased white blood cell count) as a side effect. In a small low-dose study using 280 mg/day oral EMP for 150 days, tolerability was significantly improved, with gastrointestinal irritation occurring in only 15% of men, and there was no incidence of severe cardiovascular toxicity or deep vein thrombosis. In addition, no other side effects besides slight transient elevated