Reduced incidence of rabbit endometrial neoplasia with levonorgestrel implant

To test the hypothesis that progestogens protect against the development of endometrial neoplasia, we placed polydimethylsiloxane implants (levonorgestrel or inert) into the right uterine horn at random in 114 old female rabbits. Cross-sectional uterine biopsy specimens were taken from both horns at the time of implantation and at 6, 12, and 24 months thereafter. Twenty-nine levonorgestrel-treated and 33 controls survived to the completion of the study. The incidence of endometrial neoplasia of 17.2% in the group treated with levonorgestrel was significantly less (p less than 0.05) than the 42.4% incidence observed in the control does. Before the completion of the study, one levonorgestrel-treated doe died and was found to have an endometrial tumor. When the findings of this doe are included in the report, the statistical significance is marginally lost. No endometrial neoplasia was found in the eight does with serum levonorgestrel concentrations greater than 0.12 ng/ml. Only one of the five tumors in the levonorgestrel-treated group occurred in the horn containing the levonorgestrel implant, which suggests that a dose effect is likely. Treatment with levonorgestrel decreases the incidence of endometrial neoplasia in rabbits. This finding gives further credence to the use of progestogen supplementation in women at risk for developing endometrial neoplasia.