AN EVALUATION OF THE EFFECT OF GONADOTROPIN-RELEASING-HORMONE ANALOGS AND MEDROXYPROGESTERONE ACETATE ON UTERINE LEIOMYOMATA VOLUME BY MAGNETIC-RESONANCE-IMAGING - A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL
AN EVALUATION OF THE EFFECT OF GONADOTROPIN-RELEASING-HORMONE ANALOGS AND MEDROXYPROGESTERONE ACETATE ON UTERINE LEIOMYOMATA VOLUME BY MAGNETIC-RESONANCE-IMAGING - A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL
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DOI：
10.1210/jc.76.5.1217
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发表时间：
1993-05-01
影响因子：
5.8
通讯作者：
STEINKAMPF, MP
中科院分区：
文献类型：
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作者：
CARR, BR;MARSHBURN, PB;STEINKAMPF, MP
本研究的目的是前瞻性地比较在第一个（方案A）或最后一个（方案B） 12周期间给予醋酸甲孕酮（MPA； 20mg /天）以及GnRH类似物（GnRH- A；醋酸leuprolide； 1mg /天，sc）的6个月疗程对子宫和平滑肌瘤体积、激素（雌二醇、LH和FSH）和血脂（总胆固醇、甘油三酯和高低密度脂蛋白）水平的影响。16名妇女被随机分为方案A或B，分别接受MPA或安慰剂和GnRH-a，然后在12周时分别接受安慰剂或MPA，最后12周的GnRH-a治疗间隔。通过磁共振成像确定子宫总体积、肌瘤体积和非肌瘤体积，并在研究开始时、12周和24周进行血清研究。在两种方案中，在12周时LH和雌二醇水平分别下降了基线的80-90% （P < 0.03）和55-72% (P < 0.02)，并在24周时保持在该水平。在不同方案之间或纵向上，其他实验室测试没有显著变化。方案B的子宫总体积在12周时下降到基线的73% (P < 0.04)，但在方案A中没有变化。在12周交叉后，方案A妇女的子宫总体积在24周时下降到基线的74% （P < 0.02）。方案间比较显示，在12周时方案B的子宫总体积比方案a的下降更大，但在交叉后，增加MPA与方案B的子宫总体积显著增加（方案B）相关，而在24周时方案a的子宫总体积减少（P < 0.005）。相比之下，尽管两种方案的肌瘤体积都有所下降，但在治疗期间，两组内或组间肌瘤体积均未发现显著变化。方案A和B的非肌瘤体积变化大致与子宫总体积变化平行，MPA共给药显示与gnrh - A相关的非肌瘤组织体积减少的逆转相关。我们得出结论：1)GnRH-a治疗对子宫平滑肌瘤患者子宫总体积变化的主要影响是对子宫非肌瘤组织的影响，对子宫肌瘤体积的影响较小；2) MPA似乎逆转了gnrh -a诱导的雌激素水平低下降低非肌瘤体积的效果；3)在雌二醇、促性腺激素或血脂水平方面，MPA和GnRH-a治疗没有观察到差异。因此，对于减少子宫平滑肌瘤大小的GnRH-a联合治疗方案，MPA是一种次优黄体酮。
The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time.Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.We conclude that 1) the predominant effect of GnRH-a therapy on total uterine volume changes in cases of leiomyomata uteri is on nonmyoma uterine tissue, with less of an influence on myoma volume; 2) MPA appears to reverse the effectiveness of GnRH-a-induced hypoestrogenism in decreasing nonmyoma volume; and 3) no difference was observed with respect to levels of estradiol, gonadotropins, or serum lipids between MPA administration and GnRH-a therapy. Thus, MPA is a suboptimal progestin for concomitant treatment regimens with GnRH-a directed toward reduction of the size of leiomyomata uteri.