Constantine Ginger D, Goldstein Steven R, Archer David F
From the 1EndoRheum Consultants, Malvern, PA; 2New York University School of Medicine, New York, NY; and 3Jones Institute for Reproductive Medicine, Eastern Virginia Medical Center, Norfolk, VA.
Menopause. 2015 Jan;22(1):36-43. doi: 10.1097/GME.0000000000000275.
This study aims to assess the endometrial safety of ospemifene based on phase 2/3 clinical trials of postmenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.
Endometrial safety was evaluated in a development program of six randomized, double-blind, placebo-controlled, parallel-group studies of postmenopausal women aged between 40 and 80 years who had vulvar and vaginal atrophy. Participants were randomized 1:1 to ospemifene 60 mg/day or placebo in one 6-week trial and three 12-week trials; one of the 12-week trials had a 40-week extension study. In a separate 52-week trial, women were randomized 6:1 to ospemifene 60 mg/day or placebo. Endometrial safety was assessed by endometrial histology (biopsy), transvaginal ultrasound, and gynecologic examination.
In these trials, 1,242 women who received ospemifene 60 mg/day and 924 women who received placebo were evaluable for safety. Endometrial hyperplasia occurred in less than 1% of women treated with ospemifene; no endometrial cancer was reported. The mean (SD) increase in endometrial thickness among women treated with ospemifene was 0.51 (1.54) mm at 12 weeks, 0.56 (1.61) mm at 6 months, and 0.81 (1.54) mm at 12 months. Women who received placebo had a mean (SD) increase of 0.07 (1.23) mm at 12 months.
These clinical trial data indicate that up to 52 weeks of treatment with oral ospemifene 60 mg/day was safe for the endometrium. There was no increase in the incidence of endometrial cancer or hyperplasia among postmenopausal women treated with ospemifene compared with placebo.
本研究旨在根据绝经后女性的2/3期临床试验，评估奥培米芬的子宫内膜安全性，这些女性接受每日60毫克奥培米芬治疗长达52周，与安慰剂进行对照。
在一项针对40至80岁患有外阴和阴道萎缩的绝经后女性的六项随机、双盲、安慰剂对照、平行组研究的开发项目中评估子宫内膜安全性。在一项为期6周的试验和三项为期12周的试验中，参与者按1:1随机分配至每日60毫克奥培米芬组或安慰剂组；其中一项12周试验有一项为期40周的延长期研究。在另一项为期52周的试验中，女性按6:1随机分配至每日60毫克奥培米芬组或安慰剂组。通过子宫内膜组织学（活检）、经阴道超声和妇科检查评估子宫内膜安全性。
在这些试验中，1242名接受每日60毫克奥培米芬治疗的女性和924名接受安慰剂治疗的女性可进行安全性评估。接受奥培米芬治疗的女性中，子宫内膜增生发生率低于1%；未报告子宫内膜癌病例。接受奥培米芬治疗的女性在12周时子宫内膜厚度平均（标准差）增加0.51（1.54）毫米，6个月时增加0.56（1.61）毫米，12个月时增加0.81（1.54）毫米。接受安慰剂治疗的女性在12个月时平均（标准差）增加0.07（1.23）毫米。
这些临床试验数据表明，每日口服60毫克奥培米芬治疗长达52周对子宫内膜是安全的。与安慰剂相比，接受奥培米芬治疗的绝经后女性子宫内膜癌或增生的发生率没有增加。
