Induction of epithelial neoplasms in the ovaries of guinea pigs by estrogenic stimulation

Objective. We have been searching for an animal model for ovarian epithelial neoplasms. Our previous study suggested that by giving intermediate doses of testosterone to guinea pigs it is possible to induce cystadenomas in the ovaries in 6 to 10 months. Methods. In this study we investigated the effect of different estrogens including estradiol, diethylstilbestrol (DES), estrone, dienestrol, and hexestrol in 24 guinea pigs. Five guinea pigs received sterile water and were used as controls. Results. Bilateral serous cysts were seen in the ovaries of five guinea pigs that received low (0.25 and 0.35 mg) and intermediate (0.5 and 0.7 mg) doses of estradiol for 2 to 9 months. Surface papillary neoplasms were seen in the ovaries of four guinea pigs that received DES at an intermediate dose (6 mg) and high doses (10 and 12 mg) for 3 to 12 months. The ovaries of the other guinea pigs were unremarkable. Estradiol was measured by radioimmunoassay in three guinea pigs. In the serum it ranged from 450 to 580 pg/ml, and in the ovarian cystadenomas it ranged from 1020 to 6575 pg/ml. Conclusions. (1) It is possible to induce ovarian neoplasms using estrogenic hormones. (2) The best results are obtained with intermediate doses of estradiol and DES. (3) These two hormones induce different lesions: estradiol is associated with cystic lesions and DES with surface papillary tumors. These observations, together with our previous finding that testosterone induces neoplasms with a predominantly glandular pattern, establish the guinea pig as an excellent animal to study ovarian neoplasms, confirm the significance of hormones in the development of ovarian epithelial tumors, and suggest that the different histologic appearance of ovarian epithelial neoplasms might be related to different hormonal effects.