EFFECTS OF AN ANTIPROGESTERONE (RU486) ON THE HYPOTHALAMIC-HYPOPHYSEAL-OVARIAN-ENDOMETRIAL AXIS DURING THE LUTEAL PHASE OF THE MENSTRUAL-CYCLE
EFFECTS OF AN ANTIPROGESTERONE (RU486) ON THE HYPOTHALAMIC-HYPOPHYSEAL-OVARIAN-ENDOMETRIAL AXIS DURING THE LUTEAL PHASE OF THE MENSTRUAL-CYCLE
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DOI：
10.1210/jcem-66-3-508
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发表时间：
1988-03-01
影响因子：
5.8
通讯作者：
YEN, SSC
中科院分区：
文献类型：
--
作者：
GARZO, VG;LIU, J;YEN, SSC
The impact of the antiprogesterone RU486 [17.beta.-hydroxy-11.beta.-(4-dimethylaminophenyl)17.alpha.-(1-propynyl)estra-4,9-dien-3-one] on the hypothalamic-pituitary-ovarian-endometrial axis was examined in normal cycling women during the mid (MLP)- and late (LLP) luteal phases. During the MLP, 10 women received 3 mg/kg RU486 for 3 days. During the LLP, a single dose of 600 mg RU486 was administered to 4 women, and in another 4 women a sigle dose of 3 mg/kg was given during corpus luteum rescue by hCG. Longitudinal studies with daily and frequent blood samples (every 10 min for 10 h) were conducted during 3 consecutive cycles (control-treatment-recovery). During the MLP, RU486-induced uterine bleeding occurred in all 10 women 36-72 h after the first dose. No histological evidence of endometrial breakdown was found in endometrial biopsies taken 12-24 h before the onset of bleeding. Significant decreases in LH secretion (P < 0.001) and LH pulse amplitude (P < 0.006) and blunted pituitary responses to GnRH (P < 0.01) were evident by the last treatment day, but LH pulse frequency did not change. Complete luteolysis occurred in 2 of the 10 women. Incomplete luteolysis occurred in 8 women and was associated with an initial decline of serum estradiol (P < 0.001), but not progesterone levels, followed by rebound increases (P < 0.001) in LH, estradiol, and progesterone levels 3 days later, which may have reversed the luteolytic processes and prolonged corpus luteum function. Spontaneous luteolysis ensued 3-5 days late with the onset of second episodes of uterine bleeding. For serum FSH, an early rise occurred during the luteal phase in advance of the onset of the second episodes of uterine bleeding. This rise may have resulted in early follicle recruitment and accounted for the shorter duration of the follicular phase during recovery cycles. During the LLP, the single RU486 dose resulted in significant decreases in LH pulse amplitude (P < 0.03), frequency (P < 0.05), and secretion (not significant) within 12 h. The recovery cycle was entirely normal. Corpus luteum rescue with incremental dose of hCG did not prevent uterine bleeding after RU486 treatment. These findings indicate that RU486 operates at multiple sites and implies that progesterone is important in the control of luteal function. Further, our data provide a basis for exploring the potential use of RU486 as a once a month birth control agent.
