The effect of a luteinizing hormone releasing hormone (LRH) agonist (Wy-40,972), levonorgestrel, danazol and ovariectomy on experimental endometriosis in the rat

Abstract

The effect of the LRH agonist, Wy-40,972, levonorgestrel or danazol on growth of endometrial explants in the intact female rat was studied. Sc injection of a single compound was begun 3 weeks after transplantation of a section of endometrium to the peritoneal wall. The animals were laparotomized to determine growth of the explant on day 1 of treatment. Injections were continued for 3 weeks at which time the animals were again laparotomized and the condition of the explant examined. Eight weeks after cessation of treatment the animals were sacrificed and the growth of the explant recorded. One or 30 micrograms of the LRH agonist produced a consistent inhibition of explant growth during treatment that was comparable to that obtained by ovariectomy. However, 8 weeks after cessation of injection, the majority of explants exhibited renewed growth while all of the explants in the ovariectomized rats were only visually present. These result suggest that inhibiting or eliminating ovarian steroid production alone will not produce a permanent regression of the endometrial explant. Treatment with 30 micrograms danazol produced no effect and 1, 30 or 100 micrograms levonorgestrel produced none to limited inhibition of explant growth. However, 8 weeks after cessation of treatment explants in animals treated with either levonorgestrel or danazol were smaller in size than recorded prior to treatment. Thus, the inhibiting action of the peptide is rapid, whereas that of the steroids is, apparently, delayed. The observed activity of steroidal and non-steroidal compounds in this study demonstrates the usefulness of a rat model in the study of endometriosis.