Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study
Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study
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DOI：
10.1067/mob.2002.123938
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发表时间：
2002-09-01
影响因子：
9.8
通讯作者：
Nanavati, N
中科院分区：
文献类型：
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作者：
Goldstein, SR;Nanavati, N
目的：选择性雌激素受体调节剂是与雌激素受体结合并具有混合激动和拮抗活性的新型化合物。最近，增加尿失禁已报告与激素替代疗法的使用。雷洛昔芬是一种选择性雌激素受体调节剂，不具有促子宫作用，但最近有报道称，雷洛昔芬可减少用于盆底松弛的外科手术。左美洛昔芬是一种选择性的雌激素受体调节剂，是为治疗和预防绝经后骨质疏松症的目的而开发的。研究设计：这是一项多中心前瞻性研究，年龄大于或等于65岁的骨质疏松症健康女性随机盲法接受安慰剂或左美洛昔芬0.5 mg或1.25 mg，每日作为计划的3年骨质疏松症治疗研究的一部分。进行了多次医学和妇科评估。向研究者报告不良事件，并使用世界卫生组织术语进行编码。这项研究在10个月后停止，因为大量的妇科和其他不良事件。在研究的2924名妇女中，与安慰剂相比，接受左美洛昔芬治疗的妇女白带明显增加（30% vs 3%），超声扫描显示子宫内膜厚度增加（19% vs 1%），子宫增大（17% vs 3%），子宫阴道脱垂（7% vs 2%），尿失禁（17% vs 4%）、排尿频率增加（9% vs 4%）、下腹痛（17% vs 6%）、潮热（10% vs 3%）和腿部痉挛（6% vs 0.8%）。所有这些差异都具有高度统计学意义，概率值为0.0001 each.CONCLUSION：左美洛昔芬导致绝经后骨质疏松症女性发生多种不良妇科和其他事件。
OBJECTIVE: Selective estrogen receptor modulators are novel compounds that bind to the estrogen receptor and have mixed agonistic and antagonistic activities. Recently, an increase in urinary incontinence has been reported with hormone replacement therapy use. A decrease in surgical procedures for pelvic floor relaxation has been recently reported with raloxifene, a selective estrogen receptor modulator that is not uterotropic. Levormeloxifene is a selective estrogen receptor modulator that was developed for the purpose of the treatment and prevention of postmenopausal osteoporosis.STUDY DESIGN: This was a multicentered prospective study of healthy women aged greater than or equal to65 years with osteoporosis who were randomized to blindly receive placebo or levormeloxifene 0.5 mg or 1.25 mg daily as part of a planned 3-year osteoporosis treatment study. Multiple medical and gynecologic evaluations were performed. Adverse events were reported to investigators and coded with the use of World Health Organization terminology. This study was halted after 10 months because of the large number of gynecologic and other adverse events.RESULTS: Among 2924 women who were studied, those women who were treated with levormeloxifene had a marked increase compared with placebo in leukorrhea (30% vs 3%), increased endometrial thickness on ultrasound scan (19% vs 1%), enlarged uterus (17% vs 3%), uterovaginal prolapse (7% vs 2%), urinary incontinence (17% vs 4%), increased micturition frequency (9% vs 4%), lower abdominal pain (17% vs 6%), hot flushes (10% vs 3%), and leg cramps (6% vs 0.8%). All of these differences were highly statistically significant with a probability value of .0001 for each.CONCLUSION: Levormeloxifene results in multiple adverse gynecologic and other events in postmenopausal women with osteoporosis.