绝经早期激素治疗试验结束 3 年后的大脑结构和认知。
Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.
机构信息
From the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans Hospital, Madison, WI; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
出版信息
Neurology. 2018 Apr 17;90(16):e1404-e1412. doi: 10.1212/WNL.0000000000005325. Epub 2018 Mar 21.
OBJECTIVE
The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health.
METHODS
Participants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68).
RESULTS
Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo.
CONCLUSIONS
The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT.
目的
在心血管健康状况良好的近期绝经女性中，进行了一项随机、安慰剂对照试验，研究了两种常用的绝经激素治疗（MHT）方案对脑结构和认知的影响，该试验结束 3 年后，对参与者进行了调查。
方法
参与者（年龄 42-56 岁；绝经后 5-36 个月）被随机分为以下三组之一：0.45 毫克/天口服结合马雌激素（oCEE）；50 微克/天经皮 17β-雌二醇（tE2）；或安慰剂片和贴剂，共 4 年。MHT 组每月给予 200 毫克/天的口服孕酮 12 天。基线时、4 年 MHT 结束时和 MHT 结束 3 年后（n=75）进行 MRI。一部分参与者还接受了匹兹堡复合物 B-PET（n=68）。
结果
与安慰剂组相比，oCEE 组在 4 年 MHT 期间脑室容积增加更多，但在 MHT 停止 3 年后，脑室容积的增加与安慰剂组无差异。oCEE 和 tE2 组的脑白质高信号体积增加相似，但仅在 oCEE 组中明显大于安慰剂组。tE2 组与安慰剂组相比，背外侧前额叶皮质体积的纵向下降幅度较小，这与皮质匹兹堡复合物 B 摄取量较低相关。MHT 组的总体认知变化率与安慰剂组无差异。
结论
oCEE 对 MHT 期间的整体脑结构的影响在 oCEE 停药后消退，但脑白质高信号仍在增加。tE2 组背外侧前额叶皮质体积 7 年来的相对保留表明 MHT 可能对大脑有长期影响。
证据分类
这项研究提供了 III 级证据，表明在最近接受 MHT（tE2 或 oCEE）的绝经后女性中，全球脑容量和认知功能的变化率与接受安慰剂的女性没有显著差异，这是在暴露于 MHT 3 年后测量的。
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