Evaluation of current information concerning the relationship between hormonal usage and cancer.

Abstract

In early animal experiments it was found that estrogens induced the type of excessive mitotic activity generally associated with malignant tumors in the female genital tract. The potent chemical carcinogens of the methylcholanthrene type were shown to belong to the same cyclopentenophenanthrene family as the hormonal steroids. Therefore as preparations of the female sex hormones become available there was concern as to their potential effect in the pathogenesis of cancer of the breast and of the female genital tract. In many laboratories data were developed indicating that estrogen administration is followed by reproducible tumors in 6 species of animals and in 8 organ sites. Long-term administration of high doses of synthetic progestins produced malignant tumors of the breast in beagle dogs. Norethynodrel produced ovarian tumors in mice and when given with estrogen also produced cancer of the cervix in mice. Dosage genetic strain of animals age of onset of exposure and duration of exposure have influenced results. In humans the genetic or familial factor has been shown to be important particularly in relation to breast cancer. Vaginal adenocarcinoma in girls after maternal estrogen therapy during pregnancy has been estimated to occur in .2% of cases. A definite latent period follows this intrauterine exposure. Very few of these patients have been younger than 10 years and few older than 20 years of age. Endometrial carcinoma has followed chronic treatment with stilbestrol for gonadal dysgenesis. Contraceptive users have shown a tendency toward hyperplasia or to cystic hyperplasia and a few cases of endometrial carcinoma have been reported in young women. Benign liver tumors have occurred in women taking oral contraceptives. Endometrial cancer in postmenopausal women following estrogen use has been shown to occur. The risk ratio among users has been estimated to be 7.6 times that of controls. After more than 7 years of estrogen use the risk ratio has been increased to 14 times that of controls. Progestationally active compounds have reversed the preneoplastic adenomatous hyperplasia in these cases and even induced regression of endometrial carcinomas. The incidence of breast cancer has not been shown to be increased by use of oral contraceptives. Longer observation periods are needed to confirm these findings.