@article{d7d634b8cf014d06ab3ce15ad6352f36,
title = "Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial",
abstract = "ObjectiveThe 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.MethodsParticipants (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 g/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).ResultsVentricular 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.ConclusionsThe 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 evidenceThis 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.",
author = "Kejal Kantarci and Nirubol Tosakulwong and Lesnick, {Timothy G.} and Zuk, {Samantha M.} and Lowe, {Val J.} and Fields, {Julie A.} and Gunter, {Jeffrey L.} and Senjem, {Matthew L.} and Settell, {Megan L.} and Gleason, {Carey E.} and Shuster, {Lynne T.} and Bailey, {Kent R.} and Dowling, {N. Maritza} and Sanjay Asthana and Jack, {Clifford R.} and Rocca, {Walter A.} and Miller, {Virginia M.}",
note = "Funding Information: K. Kantarci serves on the data safety monitoring board for Takeda Global Research & Development Center, Inc. She is funded by the NIH and receives research support from Avid/Eli Lilly Company. N. Tosakulwong, T. Lesnick, and S. Zuk report no disclosures relevant to the manuscript. V. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). J. Fields is funded by the NIH. J. Gunter reports no disclosures relevant to the manuscript. M. Senjem holds stock in Gilead Sciences, Inc., Inovio Pharmaceuticals, Medtronic, Oncothyreon, Inc., and PAREXEL International. M. Settell reports no disclosures relevant to the manuscript. C. Gleason is funded by the NIH. L. Shuster reports no disclosures relevant to the manuscript. K. Bailey is funded by the NIH. M. Dowling reports no disclosures relevant to the manuscript. S. Asthana is funded by the NIH. C. Jack provides consulting services for Eli Lilly. He is funded by the NIH and Alexander Family Alzheimer{\textquoteright}s Disease professorship of the Mayo Foundation. W. Rocca is funded by the NIH. V. Miller is funded by NIH. Go to Neurology.org/N for full disclosures. Funding Information: The Article Processing Charge was funded by the Mayo Clinic. Funding Information: This study is funded by the Aurora Foundation to the Kronos Longevity Research Institute and the NIH (NS66147, AG029624, AG44170, and AG057547). The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2018 American Academy of Neurology.",
year = "2018",
doi = "10.1212/WNL.0000000000005325",
language = "English (US)",
volume = "90",
pages = "E1404--E1412",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "16",
}