Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities?

Androgen deprivation therapy (ADT) is the mainstay of management of advanced-stage prostate cancer and recently has been shown to improve survival when administered in earlier stages of the disease. The oncologic benefits of ADT might be partially offset, however, by a reduction in quality of life because of adverse effects. In addition to the well-recognized adverse consequences of ADT, recent evidence suggests that ADT is associated with dyslipidemia, impaired glucose metabolism, adverse body compositional changes, and osteoporosis. Therefore, there is a pressing need to develop less toxic forms of ADT. A novel approach to this problem is the use of estrogen to induce androgen suppression. Whereas oral estrogen therapy is known to be associated with thromboembolic complications, studies of parenteral estrogen in men with prostate cancer suggest that the use of parenteral estrogen achieves target androgen suppression, does not adversely affect prothrombotic protein levels, and is not associated with adverse metabolic, skeletal, and body compositional changes when compared with conventional ADT. Herein, we review the data for parenteral estrogen use in prostate cancer, the antineoplastic mechanisms of action of estrogen in prostate cancer, the potential advantages of parenteral estrogen compared with conventional ADT, and the remaining barriers in the use of parenteral estrogen in prostate cancer.