The Roles of Estrogen and Progestin in Producing Deciduosarcoma and Other Lesions in the Rabbit

The interactions of estrogens and progestins in producing decidualization, deciduosarcoma, and other lesions in the rabbit were explored. Steroids were delivered by silicone elastomer implants placed subdermally except for oral dosing in 1 experiment. Varying doses of levonorgestrel (LNG) were given with and without estradiol (E-2) and varying doses of E-2 with and without LNG. LNG alone delivered at an estimated mean dose of 233 mug/day did not result in endometrial decidualization or deciduosarcoma. Both conditions occurred when E2 was added to the regimen and increased as the dose of E-2 was increased. Sixty mug of E-2 per day produced endometrial decidualization in all test animals in a 2-month exposure, but deciduosarcoma occurred only when LNG was also supplied and increased as the LNG dose was increased. Progesterone given with E-2 resulted in deciduosarcoma in most rabbits. Ethynylestradiol alone at 30 mug/day delivered by implants produced splenic and ovarian deciduosarcomas in 1 of 5 test animals. Adding LNG resulted in more numerous and widespread deciduosarcomas. These experiments indicate that exogenous estrogen is necessary for decidualization of the endometrium and to production of deciduosarcoma in the nonpregnant rabbit. Exogenous progestin promotes the process. Necrosis of the uterine wall tended to increase with increasing dose of estrogens.