Medicinal drugs with hormonal activity as chemopreventive agents.

Many of the most common cancers occur in sites that are under hormonal regulation by the steroid sex hormones. These include the breast, ovary, endometrium and possibly the colon for women, and the prostate and testes for men. Much information on chemoprevention of these cancers has accrued indirectly as a result of the use of estrogens and progestagens for contraception or postmenopausal hormone replacement therapy. Estrogen-based contraceptives clearly reduce the risk of ovarian cancer, but without an opposing progestagen they increase the risk of endometrial cancer. Progestagens reduce the risk of endometrial cancer and when used premenopausally appear to be able to more than counteract the carcinogenic effect of exogenous estrogens at this site. The effect of oral contraceptives on breast cancer appears to be quite minimal, but probably increases risk when taken for long periods at a young age. Recent studies suggest that the use of an agonist of leuteinizing hormone releasing hormone as a contraceptive may reduce the risk of breast cancer. Estrogens used in postmenopausal hormone replacement therapy increase the risk of both breast and endometrial cancer, but addition of a progestagen may counteract the increased risk to the endometrium. The agent most intensively under study for breast cancer prevention is tamoxifen, which has proven effectiveness as a therapeutic agent. When taken for more than two years it has been shown to reduce the occurrence of new contralateral tumours by about 50% in women who have had breast cancer. Three large international trials are currently evaluating its role in a preventive setting. For men, interest has centred on the use of 5 alpha-reductase inhibitors to block the prostatic conversion of testosterone to dehydrotestosterone and potentially inhibit the development of prostate cancer. The 5 alpha-reductase inhibitor finasteride is currently under test in a prevention trial.