Faubion Laura L, Mak Elijah, Kara Firat, Tosakulwong Nirobul, Lesnick Timothy G, Fought Angela J, Reid Robert I, Schwarz Christopher G, Kendall-Thomas June, Kapoor Ekta, Fields Julie A, Bailey Kent R, James Taryn T, Lobo Rogerio A, Manson JoAnn E, Pal Lubna, Hammers Dustin B, Brinton Eliot A, Malek-Ahmadi Michael, Cedars Marcelle, Naftolin Frederick Nicholas, Santoro Nanette, Miller Virginia M, Harman Sherman M, Dowling N Maritza, Gleason Carey E, Kantarci Kejal
Department of Radiology.
Department of Quantitative Health Sciences.
Menopause. 2025 Jul 22;32(9):818-28. doi: 10.1097/GME.0000000000002562.
To assess the long-term effects of 4 years of menopausal hormone therapy (mHT) on the brain's white matter architecture in women who initiated mHT within 3 years of menopause onset.
The Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, double-blind, randomized, placebo-controlled 4-year mHT trial with treatment arms of oral conjugated equine estrogens (oCEE), transdermal 17β-estradiol (tE2), and placebo in recently postmenopausal women. KEEPS Continuation was an observational follow-up of KEEPS participants. White matter integrity was evaluated in KEEPS Continuation participants 10 years after KEEPS completion using white matter hyperintensity volume, diffusion magnetic resonance imaging (dMRI) techniques, and cerebral infarcts. Linear regression models were fitted for each brain region to evaluate if there were differences in white matter between KEEPS treatment arms.
There was no evidence to suggest the long-term effects of 4 years of mHT on brain white matter in KEEPS Continuation participants [n=266, mean age 67 (58-73)]. No differences in dMRI metrics were found in each of the treatment arms (oCEE n=70; tE2 n=79) when compared to placebo (n=94), following a false discovery rate adjustment for multiple comparisons. There were no statistically significant differences in white matter hyperintensity volume or infarct occurrence when comparing each of the treatment arms to placebo.
We found no evidence of the long-term effect of 4-year mHT on white matter integrity when compared to placebo, consistent with emerging evidence of the safety of short-term use of mHT in recently postmenopausal women.
评估在绝经开始3年内开始接受绝经激素治疗（mHT）的女性中，4年mHT对脑白质结构的长期影响。
Kronos早期雌激素预防研究（KEEPS）是一项多中心、双盲、随机、安慰剂对照的4年mHT试验，治疗组包括口服结合马雌激素（oCEE）、经皮17β-雌二醇（tE2），安慰剂组为近期绝经的女性。KEEPS延续研究是对KEEPS参与者的观察性随访。在KEEPS完成10年后，使用脑白质高信号体积、扩散磁共振成像（dMRI）技术和脑梗死对KEEPS延续研究的参与者进行脑白质完整性评估。对每个脑区拟合线性回归模型，以评估KEEPS治疗组之间脑白质是否存在差异。
没有证据表明KEEPS延续研究的参与者（n = 266，平均年龄67岁[58 - 73岁]）接受4年mHT对脑白质有长期影响。在对多重比较进行错误发现率调整后，与安慰剂组（n = 94）相比，各治疗组（oCEE组n = 70；tE2组n = 79）的dMRI指标均未发现差异。将各治疗组与安慰剂组进行比较时，脑白质高信号体积或梗死发生率均无统计学显著差异。
与安慰剂相比，我们没有发现4年mHT对脑白质完整性有长期影响的证据，这与近期绝经女性短期使用mHT安全性的新证据一致。
