The nonsteroidal effects of diethylstilbestrol: the rationale for androgen deprivation therapy without estrogen deprivation in the treatment of prostate cancer.
OBJECTIVE
During the last 2 decades there has been an increase in the number of men with prostate cancer placed on luteinizing hormone releasing hormone (LH-RH) agonist therapy. In addition, the duration of individual therapy has extended from what was once only a few months to, in many cases, several years. As a result there has been an increase in the incidence of side effects, including osteoporosis, decreased cognitive abilities, vascular stiffness and fatigue. We explored the use of estrogen in the form of diethylstilbestrol (DES) as an alternative treatment for men with prostate cancer, and introduce the concept of androgen deprivation without estrogen deprivation. In doing so we hope to elucidate some of the nonhormonal nonsteroidal effects of DES. Furthermore, we hope to define the mechanisms by which DES can be useful when LH-RH agonist therapy or orchiectomy has failed.


METHODS
We comprehensively reviewed the literature from 1935 to the present regarding estrogen and antiandrogen therapy. Our search focused on issues pertaining to side effects, efficacy and nonsteroidal effects of antiandrogens and estrogens.


RESULTS
It is readily apparent from the literature that androgen deprivation with DES can achieve effective prostate cancer control with demonstrable benefits compared to conventional LH-RH agonist therapy. In particular, rates of bone resorption and osteoporosis are less with the use of estrogen therapies. Estrogen has a clear beneficial effect on cognitive function. The estrogen metabolite 2-methoxyestradiol has significant antiangiogenic and pro-apoptotic effects. These effects give estrogens an added anticancer effect not otherwise seen in conventional LH-RH agonist therapy.


CONCLUSIONS
The efficacy of 1 mg DES extends well beyond its androgen suppressive effects. Androgen deprivation without estrogen deprivation is a concept that deserves further attention in the urological community.
Scherr
Douglas S
DS
James Buchanan Brady Foundation, Department of Urology, New York-Presbyterian Hospital/Weill Medical College of Cornell University, 525 East 68th Street, Starr 900, New York, NY 10021, USA. dss2001@med.cornell.edu
Pitts
W Reid
WR
D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D004054:Diethylstilbestrol / Q000009:adverse effects / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000819:agonists / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol