Androgen deprivation therapy for prostate cancer - the potential of parenteral estrogen

The treatment of choice for carcinoma of the prostate for over a generation was oral estrogen but this was abandoned due to an excess of cardiovascular and thromboembolic toxicity. We now recognize that most of this toxicity relates to first pass portal circulation where hepatic metabolism of hormones, lipids and coagulation proteins is up regulated. It has been shown that most of such toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration; this avoids hepatic enzyme induction. A modest short term increase in cardiovascular morbidity (but not mortality) is compensated for by a long term cardioprotective benefit, which accrues progressively as vascular remodeling develops with time. A major advantage of estrogen therapy is protection against the effects of the andropause (cf female menopause), which with conventional androgen suppression causes significant morbidity including osteoporotic fracture, hot flushes, lethargy and cognitive dysfunction. Parenteral estrogen therapy is also much cheaper than contemporary endocrine therapy, with substantial economic benefits for health providers.