比较随机分配至低剂量口服结合雌激素或经皮雌二醇加微粒化孕酮组与安慰剂组的女性更年期症状的纵向变化： Kronos早期雌激素预防研究
Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study.
作者信息
Santoro Nanette, Allshouse Amanda, Neal-Perry Genevieve, Pal Lubna, Lobo Rogerio A, Naftolin Frederick, Black Dennis M, Brinton Eliot A, Budoff Matthew J, Cedars Marcelle I, Dowling N Maritza, Dunn Mary, Gleason Carey E, Hodis Howard N, Isaac Barbara, Magnani Maureen, Manson JoAnn E, Miller Virginia M, Taylor Hugh S, Wharton Whitney, Wolff Erin, Zepeda Viola, Harman S Mitchell
机构信息
1Department of Obstetrics & Gynecology 2Department of Biostatistics, University of Colorado School of Medicine, Aurora, CO 3Department of Obstetrics, Gynecology & Women's Health and Neurosciences, Albert Einstein College of Medicine, Bronx, NY 4Department of Obstetrics & Gynecology, Yale University School of Medicine, New Haven, CT 5Department of Obstetrics & Gynecology, Columbia University College of Physicians and Surgeons, New York, NY 6Department of Obstetrics & Gynecology, New York University School of Medicine, New York, NY 7Department of Epidemiology & Biostatistics, University of California at San Francisco, San Francisco, CA 8Utah Foundation for Biomedical Research, Salt Lake City, UT 9Department of Cardiology, Los Angeles Biomedical Research Institute at Harbor UCLA, Torrance, CA 10Department of Obstetrics & Gynecology, University of California at San Francisco, San Francisco, CA 11Departments of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 12Kronos Longevity Research Institute, Phoenix, AZ 13Department of Medicine and Public Health, University of Wisconsin, Madison, WI 14Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA 15Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 16Departments of Surgery and Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 17Department of Neurology, Emory University, Atlanta, GA 18Department of Reproductive Biology and Medicine, National Institutes of Health, Bethesda, MD 19Department of Medicine, Endocrine Division, Phoenix VA Health Care System, Phoenix, AZ.
出版信息
Menopause. 2017 Mar;24(3):238-246. doi: 10.1097/GME.0000000000000756.
OBJECTIVE
The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years.
METHODS
A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling.
RESULTS
Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity.
CONCLUSIONS
Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.
目的
本研究的目的是比较两种形式的绝经激素疗法在4年内缓解绝经后早期女性血管舒缩症状、失眠和易怒症状方面的疗效。
方法
共有727名年龄在42至58岁之间、处于末次月经后3年内的女性被随机分组，分别接受口服结合雌激素（o-CEE）0.45毫克（n = 230）或经皮雌二醇（t-E2）50微克（n = 225；两者均每月加用微粒化孕酮200毫克，共12天），或安慰剂（PBO；n = 275）。在筛查时以及随机分组后6、12、24、36和48个月记录绝经症状。在意向性分析中，使用精确χ检验按治疗组比较基线时和每个随访时间点有症状女性的比例差异。使用广义线性混合效应模型检验种族/族裔和体重指数对治疗效果的差异。
结果
与PBO相比，随机接受任何一种活性激素治疗的女性在6个月时，中度至重度潮热（从基线时的44%降至PBO组的28.3%、t-E2组的7.4%和o-CEE组的4.2%）和盗汗（从基线时的35%降至PBO组的19%、t-E2组的5.3%和o-CEE组的4.7%）显著减少（两种症状的P均<0.001），活性治疗组之间无显著差异。所有组的失眠和易怒症状从基线至随机分组后6个月均有所减轻。与PBO相比，两个活性治疗组的失眠症状均有间歇性减轻，o-CEE在36和48个月时比PBO更有效（P = 0.002和0.05），t-E2在48个月时比PBO更有效（P = 0.004）。与PBO相比，两种激素治疗均未对易怒症状产生显著影响。活性治疗与PBO相比的症状缓解情况未因体重指数或种族/族裔而有显著改变。
结论
绝经后不久的女性使用低于常规剂量的口服或经皮雌激素时，潮热和盗汗症状有相似且显著的减轻。这些减轻在4年内持续存在。与PBO相比，两种激素方案的失眠症状均有间歇性减轻。
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