Chemoprevention strategies for prostate cancer: the role of 5 alpha-reductase inhibitors.
Prostate cancer is a major health problem for the aging male population. Despite hormonal dependence, the inevitable emergence of androgen insensitive tumors, which have a dismal prognosis, highlights the need to develop prevention strategies such as chemoprevention. An acceptable agent must interfere with either the process of carcinogenesis or tumor growth, and have minimal toxicity. In clinical studies, 5 alpha-reductase inhibitors have been shown to suppress serum and intraprostatic levels of dihydrotestosterone, an important promoter of prostate cancer, leading to reduction in prostate size and suppression of glandular cell activity as measured by prostate specific antigen secretion. In addition, 5 alpha-reductase inhibitors have demonstrated an excellent safety profile and tolerability in 12 month controlled clinical trials. No significant metabolic effects have been observed in gonadotropin secretion, spermatogenesis, serum lipids or glucose tolerance. The efficacy and safety of 5 alpha-reductase inhibitors in studies to date, combined with the androgen dependence of tumor production, strongly supports investigating their use for chemoprevention of prostate cancer.
Gormley
G J
GJ
Department of Endocrinology and Metabolism, Merck Research Laboratories, Rahway, New Jersey 07065.
D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000728:Androgens / Q000502:physiology; D000736:Androstenes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology / Q000627:therapeutic use; D018120:Finasteride; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology / Q000503:physiopathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000503:physiopathology / Q000517:prevention & control*
D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D000736:Androstenes; D001378:Azasteroids; D018120:Finasteride