Researchers led by Professor Natalie L. Rasgon from Stanford University Medical Center, set out to to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia.
The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT-) therapy following an average of 10 years of use.
The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET).
Longitudinal FDG-PET data were available for 45 study completers.
Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT.
Women who discontinued 17-β estradiol (17βE)-based HT, as well as women who continued conjugated equine estrogen (CEE)-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC) area.
Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE).
Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT.
In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease.
The researchers intend to repeat the study using a lerge number of women with no risk factors for Alzheimer's disease.
Dr Rasgon has been involved in longitudinal placebo-controlled neuroendocrine studies for nearly two decades, and she has been involved in neuroendocrine and brain imaging studies of estrogen effects on depressed menopausal women for the last eight years.
Rasgon NL, Geist CL, Kenna HA, Wroolie TE, Williams KE, Silverman DH. Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia. PLoS One. 2014 Mar 12;9(3):e89095. doi: 10.1371/journal.pone.0089095. eCollection 2014.
Content updated 5 May 2014