Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.
A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls, uterine lymphatics, and in 4 of 13 (31%) rabbits that survived 2 years of treatment, the tumors metastasized to the lungs. Several deciduosarcomas appeared to arise within the spleen or other abdominal organs. Other drug-related lesions included uterine or vaginal polyps, endometrial atrophy, and focal necrosis and mineralization of the uterine wall. Cells from several deciduosarcomas failed to produce tumors in nude mice or to colonize on soft agar. No decidualization or decidual neoplasms were seen in the controls.
D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000633:toxicity*; D003656:Decidua; D004338:Drug Combinations; D004343:Drug Implants; D004717:Endometrium / Q000648:ultrastructure; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D002820:Hydatidiform Mole, Invasive / Q000209:etiology / Q000473:pathology*; D016912:Levonorgestrel; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009644:Norgestrel / Q000008:administration & dosage / Q000633:toxicity*; D010053:Ovary / Q000473:pathology; D011127:Polyps / Q000473:pathology; D011247:Pregnancy; D011817:Rabbits; D012826:Silicone Elastomers; D013154:Spleen / Q000473:pathology; D014594:Uterine Neoplasms / Q000209:etiology / Q000473:pathology*; D014599:Uterus / Q000473:pathology
D003271:Contraceptive Agents, Female; D004338:Drug Combinations; D004343:Drug Implants; D012826:Silicone Elastomers; D009644:Norgestrel; D004958:Estradiol; D016912:Levonorgestrel