New York University School of Medicine, New York, NY 10016, USA.
Menopause. 2012 Jan;19(1):41-7. doi: 10.1097/gme.0b013e318223bbf4.
The aim of this study was to report the gynecologic safety findings from the Generations trial, a phase 3 study of the selective estrogen receptor modulator (SERM), arzoxifene.
A predefined objective of the trial was to evaluate the effects of arzoxifene on the genital tract. Gynecologic examinations were performed yearly, and further gynecologic assessment, including endometrial biopsy, was performed in a predefined subset of women and in those who developed vaginal bleeding.
Overall, 9,354 women were randomized (4,678 to placebo, 4,676 to arzoxifene 20 mg/d). There were 13 adjudicated cases of endometrial cancer (placebo, 4 cases; arzoxifene, 9 cases: P = 0.165) and 6 cases of endometrial hyperplasia (placebo, 2 cases; arzoxifene, 4 cases). Endometrial thickness, assessed at 24- and 36-month transvaginal ultrasounds in a subset of women, increased slightly in women assigned to arzoxifene compared with baseline and women in placebo. At the last measurement, 3 (1.7%) women assigned to placebo and 21 (10.2%) assigned to arzoxifene had an endometrial thickness greater than 5 mm (P < 0.001 for difference between treatment groups). Endometrial polyps were more common in women treated with arzoxifene (n = 37) than in women treated with placebo (n = 18; P < 0.05). Vulvular and vaginal inflammation, including mycotic infections, and vaginal discharge were reported more frequently in women treated with arzoxifene than in women treated with placebo, as were urinary tract infections.
Gynecologic events were generally more common in women treated with arzoxifene than in women treated with placebo. The gynecologic effects of arzoxifene seem to differ from those of raloxifene, although both SERMs have a benzothiophene structure. Although all SERMs influence cells through the estrogen receptor, they need to be evaluated independently in terms of their effects on various tissues, including the genital tract.
本研究旨在报告选择性雌激素受体调节剂（SERM）阿佐昔芬的 3 期 Generations 试验的妇科安全性结果。
该试验的一个预设目标是评估阿佐昔芬对生殖道的影响。每年进行妇科检查，并对包括子宫内膜活检在内的进一步妇科评估在预定的女性亚组和出现阴道出血的女性中进行。
共有 9354 名女性被随机分配（安慰剂 4678 例，阿佐昔芬 20mg/d 4676 例）。共有 13 例子宫内膜癌（安慰剂 4 例，阿佐昔芬 9 例）和 6 例子宫内膜增生（安慰剂 2 例，阿佐昔芬 4 例）经裁决。与基线相比，接受阿佐昔芬治疗的女性和安慰剂组的女性的子宫内膜厚度在接受阿佐昔芬治疗的女性中略有增加。在最后一次测量时，3 名（1.7%）安慰剂组和 21 名（10.2%）阿佐昔芬组的女性子宫内膜厚度大于 5mm（两组间差异 P<0.001）。与安慰剂组（n=18）相比，阿佐昔芬组（n=37）的子宫内膜息肉更为常见（P<0.05）。与安慰剂组相比，阿佐昔芬组的外阴和阴道炎症（包括真菌性感染和阴道分泌物）和尿路感染更为常见。
与安慰剂组相比，接受阿佐昔芬治疗的女性的妇科事件更为常见。尽管两种 SERM 都具有苯并噻吩结构，但阿佐昔芬的妇科作用似乎与雷洛昔芬不同。虽然所有 SERM 都通过雌激素受体影响细胞，但它们需要在其对包括生殖道在内的各种组织的影响方面进行独立评估。
