Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial

作者：Kantarci Kejal^*; Tosakulwong Nirubol; Lesnick Timothy G; Zuk Samantha M; Lowe Val J; Fields Julie A; Gunter Jeffrey L; Senjem Matthew L; Settell Megan L; Gleason Carey E; Shuster Lynne T; Bailey Kent R; Dowling N Maritza; Asthana Sanjay; Jack Clifford R Jr; Rocca Walter A; Miller Virginia M

来源：Neurology, 2018, 90(16): E1404-E1412.

DOI：10.1212/WNL.0000000000005325

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 mu g/d transdermal 17 beta-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 thatmHTmay 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.

• 出版日期2018-4-17