Effects of a cyclic steroid contraceptive regimen on mammary gland tumor induction in rats.

A steroid antifertility combination was administered cyclincally to female rats in order to simulate the intermittent schedule of oral contraception used by women. Administration of the compound Enovid E (EE) was begun in Sprague-Dawley rats of 45 days of age soon after puberty. The dose was the same throughout the experiment consisting of 1 mg norethinodrel and 40 mcg mestranol in 1/2 ml sesame oil given by gavage before noon. The compound was withheld during estrus metestrus and early diestrus to allow the maturation of a new set of follicles. A normally cycling animal received the compound on 3 of 5 successive days. Control animals were given the vehicle in a similar routine. The carcinogen 712-dimethylbenz alpha anthracene (DMBA) was administered in a single intragastric dose of 20 mg in 1 ml of sesame oil to half of the rats at age 55 days approximately 10 days after beginning the cyclic steroid ingestion. The other animals received the oil only. Necropsies were scheduled at ages 100 200 and 365 days after periods of enovid treatment equivalint to 10 30 and 60 cycles. There were alterations in endocrine and target organs which were more evident after the equivalint of 10 cycles of treatment than after 30 or 60 estrus cycles. The enovid rats also experienced an altered growth pattern. Following a single dose of the carcinogen DMBA there was a latency in development and modified carcinogenic potential of induced mammary tumors. The latency was accounted for by the slower rate of growth of the enovid animals. It is postulated that the modified carcinogenic response may be related to the early alteration in internal hormonal environment associated with the enovid treatment.