Departments of Surgery and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN.
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY.
Menopause. 2019 Sep;26(9):1071-1084. doi: 10.1097/GME.0000000000001326.
The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative.
The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n = 727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT).
After 4 years, neither HT affected the rate of increase in CIMT. There was a trend for reduced accumulation of coronary artery calcium with o-CEE. There were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated a positive effect on mood with o-CEE, and reduced hot flashes, improved sleep, and maintenance of bone mineral density with both treatments. Sexual function improved with t-E2. There were no significant effects of either treatment on cognition, breast pain, or skin wrinkling. Variants of genes associated with estrogen metabolism influenced the age of menopause and variability in effects of the HT on CIMT. Platelet activation associated with the development of white matter hyperintensities in the brain.
KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.
Kronos 早期雌激素预防研究（KEEPS）旨在解决理解及时绝经激素治疗（HT）对心血管健康和绝经后其他影响的空白，该研究是在妇女健康倡议提前终止后进行的。
KEEPS 是一项随机、双盲、安慰剂对照试验，旨在测试以下假设：在健康、近期绝经的女性（n=727）中开始 HT（口服结合雌激素 [o-CEE] 或经皮 17β-雌二醇 [t-E2]）是否会减缓颈动脉内膜中层厚度（CIMT）变化所衡量的动脉粥样硬化进展。
4 年后，HT 均未影响 CIMT 的增加速度。o-CEE 有减少冠状动脉钙积累的趋势。没有严重的不良反应，包括静脉血栓形成。几项辅助研究表明，o-CEE 对情绪有积极影响，减少热潮红、改善睡眠和维持骨密度，两种治疗方法均有效果。t-E2 改善了性功能。两种治疗方法均未对认知、乳房疼痛或皮肤皱纹产生显著影响。与雌激素代谢相关的基因变体影响绝经年龄和 HT 对 CIMT 的影响的可变性。血小板激活与大脑白质高信号的发展有关。
KEEPS 及其辅助研究支持了 HT 在近期绝经后女性中的应用价值和安全性，并为未来研究提供了优化 HT 和绝经后女性健康的视角。KEEPS 延续研究继续探讨这些问题。
