336. The effect of intrauterine progesterone on the hypothalaniic-pituitarv-ovarian axis in baboons

The intrauterine administration of progesterone for human contraceptive purposes results in a pregnancy rate of less than 1%. Although many oral contraceptives reportedly act by suppressing the hypothalamic-pituitary-ovarian axis the mechanisms of action of intrauterine progesterone are not understood. The present study was undertaken to determine if there are measurable extrauterine effects from progesterone delivered to the uterine lumen at constant rate. Baboons were inserted transcervically with either a Lippes loop A (LL) or a Progestasert Uterine Therapeutic System (US) which delivers progesterone at a rate of 65 mcg/24 hours. Preinsertion and posttreated cycles of each baboon served as control cycles. Blood samples taken every other day throughout the menstrual cycle were measured for luteinizing hormone estradiol and progesterone by radioimmunoassay. The presence of a UTS had no effect on the menstrual cycle length (32 + or - 1.8 days control 34.3 + or - 1.6 days UTS); however 2 of 3 baboons with Lippes loop had treated cycles consistenly shorter than their control cycles. Maximum levels of LH occurred 18 days after the onset of menses and had a mean plus or minus standard error of 1706 + or - 311 1588 + or - 337 1557 + or - 282 ng/ml for control LL and UTS respectively. Estradiol levels were maximal 1-4 days prior to maximum LH levels and had mean concentrations of 186 + or - 52 138 + or - 16 and 168 + or - 36 pg/ml for control LL and UTS respectively. Peak progesterone was 5.6 + or - 1 8.1 + or - 2 and 5.9 + or - 1.9 ng/ml for control LL and UTS respectively. Patterns of LH estradiol and progesterone secretion were similar for the control and treated cycles. It was concluded that continuous administration of 65-mcg progesterone/24 hours during the treatment period did not have extrauterine effects and that the contraceptive effectiveness of intrauterine progesterone occurs at the uterine level. (FULL TEXT)