Delmas P D, Pornel B, Felsenberg D, Stakkestad J A, Radowicki S, Garnero P, Hardy P, Dain M P, Petitier B
Service de Rhumatologie, Hôpital Edouard Herriot, Lyon, France.
Am J Obstet Gynecol. 2001 Jan;184(2):32-40. doi: 10.1067/mob.2001.108328.
A total of 325 of 569 postmenopausal women who were initially recruited into two 2-year, double-blind, placebo-controlled, dose-ranging studies of a matrix transdermal formulation of 17beta-estradiol (Menorest) participated in open-label extensions for a third year.
Those patients originally randomly assigned to receive 17beta-estradiol continued active treatment with dosages of 25, 50, 75, or 100 microg/d, whereas those originally randomly assigned to receive a placebo patch were switched to an active patch of identical size that delivered 17beta-estradiol at 25, 50, 75, or 100 microg/d. Follow-up was conducted, and bone density and other parameters were compared.
Overall, gains in bone mass were maintained in patients who received 3 years of active treatment. In patients originally randomly assigned to receive placebo, initial losses in bone mass during the first 2 years were reversed and replaced with marked increases after the switch to active treatment. All patients who had initially received placebo showed significant, dose-related, clinically relevant increases (2.77% +/- 0.99%; P =.0048; to 7.36% +/- 0.74%; P =.0001) in lumbar spine bone mineral density relative to the end of the second year of the original study; smaller final-year increases were noted among the patients who had been actively treated for all 3 years. Similar trends were reported for femoral, trochanter, and total hip bone mineral densities. Mean total body bone mineral density either increased or remained unchanged in all dosage groups. These results were accompanied by parallel changes in levels of serum and urinary markers of bone turnover, with all markers approaching or returning to premenopausal levels by month 36. The high tolerability of this formulation during years 1 and 2 was maintained during year 3; 5.5% of patients withdrew from treatment because of adverse events in the final year.
The Menorest formulation of transdermal 17beta-estradiol maintained bone mineral density gains in postmenopausal women and was well tolerated through a 3-year treatment period. It was also effective in reversing the initial bone loss associated with late commencement of therapy.
在最初招募进入两项为期2年的关于17β-雌二醇基质透皮制剂（Menorest）的双盲、安慰剂对照、剂量范围研究的569名绝经后女性中，共有325名女性参与了为期第三年的开放标签扩展研究。
那些最初随机分配接受17β-雌二醇治疗的患者继续接受25、50、75或100μg/d剂量的积极治疗，而那些最初随机分配接受安慰剂贴片的患者则改用相同大小的活性贴片，该贴片以25、50、75或100μg/d的剂量释放17β-雌二醇。进行随访，并比较骨密度和其他参数。
总体而言，接受3年积极治疗的患者骨量增加得以维持。在最初随机分配接受安慰剂的患者中，最初两年期间的骨量损失得以逆转，在改用积极治疗后被显著增加所取代。所有最初接受安慰剂的患者相对于原研究第二年结束时，腰椎骨矿物质密度均出现了显著的、与剂量相关的、具有临床意义的增加（2.77%±0.99%；P=0.0048；至7.36%±0.74%；P=0.0001）；在所有3年都接受积极治疗的患者中，最后一年的增加幅度较小。股骨、转子和全髋骨矿物质密度也报告了类似趋势。所有剂量组的平均全身骨矿物质密度均增加或保持不变。这些结果伴随着骨转换的血清和尿液标志物水平的平行变化，到第36个月时，所有标志物均接近或恢复到绝经前水平。该制剂在第1年和第2年的高耐受性在第3年得以维持；最后一年有5.5%的患者因不良事件退出治疗。
透皮17β-雌二醇的Menorest制剂在绝经后女性中维持了骨矿物质密度的增加，并且在3年的治疗期内耐受性良好。它还有效地逆转了与治疗开始较晚相关的初始骨质流失。
