Mirkin Sebastian, Pinkerton JoAnn V, Kagan Risa, Thompson John R, Pan Kaijie, Pickar James H, Komm Barry S, Archer David F
1 Pfizer Inc , Collegeville, Pennsylvania.
2 University of Virginia Health System , Charlottesville, Virginia.
J Womens Health (Larchmt). 2016 May;25(5):431-42. doi: 10.1089/jwh.2015.5351. Epub 2016 Apr 8.
To evaluate gynecologic safety of conjugated estrogens/bazedoxifene treatment for menopausal symptoms and osteoporosis prevention in nonhysterectomized women.
We pooled data from five randomized, placebo-controlled trials of conjugated estrogens 0.625 mg/bazedoxifene 20 mg (n = 1583), conjugated estrogens 0.45 mg/bazedoxifene 20 mg (n = 1585), and placebo (n = 1241). Gynecologic safety was evaluated by pelvic examination, Papanicolaou smear, endometrial biopsy, transvaginal ultrasound, mammogram, adverse events, and diary records of vaginal bleeding and breast pain/tenderness. Incidence rates and relative risks (RR) versus placebo were calculated with inverse variance weighting. Data for conjugated estrogens 0.45 mg/medroxyprogesterone acetate 1.5 mg, an active comparator in two trials (n = 399), are included for comparison.
Endometrial hyperplasia occurred in <1% (n = 4 [0.3%], 2 [0.2%], 1 [0.5%], and 2 [0.2%] for conjugated estrogens 0.625 mg/bazedoxifene 20 mg, conjugated estrogens 0.45 mg/bazedoxifene 20 mg, conjugated estrogens/medroxyprogesterone acetate, and placebo). There was one endometrial cancer, which occurred with conjugated estrogens 0.45 mg/bazedoxifene 20 mg (0.44/1000 woman-years [95% confidence interval (CI), 0.00-2.37]; RR versus placebo 0.91 [95% CI, 0.17-4.82]). There were seven cases of breast cancer: four with conjugated estrogens 0.45 mg/bazedoxifene 20 mg (1.00/1000 woman-years [95% CI, 0.00-3.21] RR 1.11 [95% CI, 0.33-3.78]), two with placebo, and one with conjugated estrogens/medroxyprogesterone acetate. Unlike conjugated estrogens/medroxyprogesterone acetate, conjugated estrogens/bazedoxifene did not increase breast density, breast pain/tenderness, or vaginal bleeding versus placebo. No active treatment increased ovarian cysts.
Conjugated estrogens/bazedoxifene provides endometrial protection without increasing breast pain/density, vaginal bleeding, or ovarian cysts in nonhysterectomized postmenopausal women studied up to 2 years.
评估结合雌激素/巴多昔芬治疗未行子宫切除术女性的绝经症状及预防骨质疏松的妇科安全性。
我们汇总了五项随机、安慰剂对照试验的数据，这些试验涉及结合雌激素0.625毫克/巴多昔芬20毫克（n = 1583）、结合雌激素0.45毫克/巴多昔芬20毫克（n = 1585）和安慰剂（n = 1241）。通过盆腔检查、巴氏涂片、子宫内膜活检、经阴道超声、乳房X光检查、不良事件以及阴道出血和乳房疼痛/压痛的日记记录来评估妇科安全性。采用逆方差加权法计算发病率和与安慰剂相比的相对风险（RR）。纳入了两项试验中作为活性对照的结合雌激素0.45毫克/醋酸甲羟孕酮1.5毫克的数据（n = 399）用于比较。
子宫内膜增生发生率<1%（结合雌激素0.625毫克/巴多昔芬20毫克组为4例[0.3%]、结合雌激素0.45毫克/巴多昔芬20毫克组为2例[0.2%]、结合雌激素/醋酸甲羟孕酮组为1例[0.5%]、安慰剂组为2例[0.2%]）。发生了1例子宫内膜癌，出现在结合雌激素0.45毫克/巴多昔芬20毫克组（0.44/1000妇女年[95%置信区间（CI），0.00 - 2.37]；与安慰剂相比的RR为0.91[95%CI，0.17 - 4.82]）。有7例乳腺癌：结合雌激素0.45毫克/巴多昔芬20毫克组4例（1.00/1000妇女年[95%CI，0.00 - 3.21]，RR为1.11[95%CI，0.33 - 3.78]），安慰剂组2例，结合雌激素/醋酸甲羟孕酮组1例。与结合雌激素/醋酸甲羟孕酮不同，与安慰剂相比，结合雌激素/巴多昔芬不会增加乳房密度、乳房疼痛/压痛或阴道出血。没有活性治疗会增加卵巢囊肿。
在长达2年的研究中，结合雌激素/巴多昔芬在未行子宫切除术的绝经后女性中提供了子宫内膜保护，且不会增加乳房疼痛/密度、阴道出血或卵巢囊肿。
