Contraceptive steroids and the mammary gland: is there a hazard?--Insights from animal studies.

The safety of synthetic steroid hormones to be used for contraception in the human female is tested in rats, beagle dogs, and (once marketing starts) in monkeys. Because early studies did not show a mammary tumor stimulating effect in the human, in contrast to findings in the dog, many objections have been raised to the use of the dog for these toxicity studies. It has been claimed that the dog is unique in its sensitivity to the mammary tumor promoting effect of progestins and that this tumorigenic effect results from progestin-induced growth hormone (GH) induction. A thorough review of the literature does not support these claims. Tumor stimulatory effects of progesterone or synthetic progestins can be observed under some conditions in rodents as well as in cats and monkeys. In addition, recent evidence suggests a role for progesterone in mammary tumorigenesis in the human, and contraceptive steroids may also not be completely without risk. While the suggested role for GH in dog mammary tumorigenesis is far from proven, such a role cannot be excluded in the other species. Whether tumor stimulatory effects of sex steroids are based upon induction of proliferation in target cells or upon genotoxic effects or both is not yet certain.