lutrelin-acetate and Endometriosis

Levonorgestrel, a progestational steroid, and the more widely used antigonadotropin, danazol have been used in the treatment of endometriosis. Both of these agents decrease serum levels of HDL cholesterol. Recently, GnRH agonists came into use for treatment of endometriosis. Our objective in this study was to compare the effects of levonorgestrel and a GnRH analog on serum cholesterol levels in rhesus monkeys being treated for surgically induced endometriosis. A high dose of levonorgestrel significantly reduced total serum cholesterol and HDL cholesterol during a 12-week treatment period. Levonorgestrel had no significant effects on the concentration of LDL/VLDL cholesterol or the percentage of total cholesterol in the HDL fraction. Conversely, the GnRH agonist had no significant effect on total serum cholesterol, HDL cholesterol, LDL/VLDL cholesterol, or the percentage of HDL cholesterol. Because the concentration of HDL cholesterol is closely correlated with atherosclerotic risk, this factor should be weighed in the overall risk/benefit analysis for the patient with endometriosis.

Topics: Animals; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Endometriosis; Female; Gonadotropin-Releasing Hormone; Levonorgestrel; Lipoproteins; Lipoproteins, VLDL; Macaca mulatta; Norgestrel; Uterine Neoplasms

The use of a GnRH agonist or a progestational steroid (levonorgestrel) for the treatment of endometriosis in monkeys was compared. Four monkeys with spontaneous endometriosis were treated for 6 months with a continuous infusion of a GnRH agonist (25 micrograms/day). Five animals with surgically induced endometriosis were treated with the same agonist for 3 months. An additional group of five monkeys with surgically induced endometriosis was treated orally with levonorgestrel (1 mg/kg X day), while a final group of four monkeys served as untreated controls. During agonist treatment, the four monkeys with spontaneous endometriosis gained body weight and had a greater than 80% decline in cyst size (representing a decline in secretory activity). Monkeys with surgically induced endometriosis had almost total resolution of endometrial lesions during agonist treatment, which was maintained throughout a 4-month posttreatment period. After initial stimulation at the onset of the GnRH agonist infusion, serum LH, FSH, estradiol, and progesterone levels decreased to near the levels of detection, where they remained until treatment was terminated. In comparison, levonorgestrel reduced endometrial lesion size, but the monkeys did not resume normal cycles as early as those treated with the agonist. Levonorgestrel-treated monkeys had normal serum LH and FSH levels, but low serum estradiol and progesterone levels. The results of this study indicate that either continuous infusion of a GnRH agonist or administration of levonorgestrel is effective for treating endometriosis in monkeys. The hormonal data suggest that the GnRH agonist acts at the level of the hypothalamus and pituitary, whereas levonorgestrel acts at the ovarian level.

Topics: Animals; Disease Models, Animal; Endometriosis; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Infusion Pumps; Levonorgestrel; Luteinizing Hormone; Macaca mulatta; Menstrual Cycle; Monkey Diseases; Norgestrel; Progesterone

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.

Topics: Animals; Castration; Contraceptives, Oral, Combined; Danazol; Endometriosis; Endometrium; Female; Gonadotropin-Releasing Hormone; Levonorgestrel; Models, Biological; Norgestrel; Peritoneal Cavity; Pregnadienes; Rats; Rats, Inbred Strains; Time Factors