O D Slayden1, K Chwalisz, R M Brenner. 1. Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton OR 97006, USA.
Abstract
BACKGROUND: A reliable means of menstrual suppression would greatly improve the quality of life for women. Information is lacking on the direct endometrial effects and appropriate dosages of new antiprogestins that may be useful for this purpose. METHODS: The current work evaluated three different systems in macaque monkeys. First, the range of doses of two relatively new antiprogestins, ZK 137 316 and ZK 230 211, that would block progesterone action directly on the endometrium in artificially cycled, spayed rhesus macaques; second, the direct endometrial effects of ZK 230 211, a type III antiprogestin; and third, investigation of whether endometrial-suppressive doses administered chronically to intact, cycling monkeys could be used for reversible, menstrual suppression. RESULTS: The results in naturally cycling animals showed that ZK 137 316 blocked menstruation in all animals, but doses of 0.05 mg/kg blocked ovulation in 55.5% of animals and doses of 0.1 mg/kg blocked ovulation in 66.6% of the animals. However, all doses of ZK 230 211 that blocked menstruation also blocked ovulation. All progesterone antagonist (PA)-treated animals, regardless of dose, maintained normal follicular phase concentrations of oestradiol and returned to normal menstrual cyclicity within 15--41 days post-treatment. Therefore ZK 137 316, depending on dose, can allow ovulation but block menstruation, while ZK 230 211, a much more potent PA, blocks both ovulation and menstruation at all effective doses. Both PAs block unopposed oestrogenic action on the endometrium through their antiproliferative effects. CONCLUSIONS: Reversible amenorrhoea can be achieved with these two PAs, and they can protect the endometrium from the effects of unopposed oestrogen whether or not ovulation is blocked. Chronic, low dose PA treatment may provide a new option for women who wish to suppress their menstrual periods.
BACKGROUND: A reliable means of menstrual suppression would greatly improve the quality of life for women. Information is lacking on the direct endometrial effects and appropriate dosages of new antiprogestins that may be useful for this purpose. METHODS: The current work evaluated three different systems in macaque monkeys. First, the range of doses of two relatively new antiprogestins, ZK 137 316 and ZK 230 211, that would block progesterone action directly on the endometrium in artificially cycled, spayed rhesus macaques; second, the direct endometrial effects of ZK 230 211, a type III antiprogestin; and third, investigation of whether endometrial-suppressive doses administered chronically to intact, cycling monkeys could be used for reversible, menstrual suppression. RESULTS: The results in naturally cycling animals showed that ZK 137 316 blocked menstruation in all animals, but doses of 0.05 mg/kg blocked ovulation in 55.5% of animals and doses of 0.1 mg/kg blocked ovulation in 66.6% of the animals. However, all doses of ZK 230 211 that blocked menstruation also blocked ovulation. All progesterone antagonist (PA)-treated animals, regardless of dose, maintained normal follicular phase concentrations of oestradiol and returned to normal menstrual cyclicity within 15--41 days post-treatment. Therefore ZK 137 316, depending on dose, can allow ovulation but block menstruation, while ZK 230 211, a much more potent PA, blocks both ovulation and menstruation at all effective doses. Both PAs block unopposed oestrogenic action on the endometrium through their antiproliferative effects. CONCLUSIONS: Reversible amenorrhoea can be achieved with these two PAs, and they can protect the endometrium from the effects of unopposed oestrogen whether or not ovulation is blocked. Chronic, low dose PA treatment may provide a new option for women who wish to suppress their menstrual periods.