Estrogen in Patients with Prostatic Cancer An Assessment of the Risks and Benefits

Abstract

Estrogen therapy of patients with prostatic carcinoma appears to be at least as effective in antitumour activity as surgical castration: the recent therapeutic alternative of gonadorelin (gonadotrophin-releasing hormone) analogues has not to date been shown to improve patient outcome. Oral estrogen therapy in these patients increases the incidence of arterial ischaemic events, thromboembolic events and congestive heart failure. A plausible mechanism behind the enhanced cardiovascular morbidity is an increase in the formation of proteins synthesised by the liver, including coagulation factors. Oral estrogens induce a 'hypercoagulable state' which can be expected to have an adverse influence on the cardiovascular system. The effect of estrogen on cholesterol metabolism is likely to be beneficial for the cardiovascular system, with decreased levels of the atherogenic low density lipoprotein (LDL) cholesterol and increased levels of the putatively beneficial high density lipoprotein (HDL) cholesterol. The effects of estrogen on platelets and cardiovascular prostanoids are difficult to evaluate at present. A possible approach to reduce its impact on the liver, and thereby possibly to minimise the risk of cardiovascular side effects, is parenteral administration. The promising results obtained in a pilot study of parenteral estrogen therapy in patients with prostatic carcinoma await confirmation in a randomised study, but where treatment with estrogen is considered for these patients, it may be that parenteral administration would be preferable.