Cyclical, long-term estrogen injections protected brain cells from age-related deterioration, according to a new study conducted at Mount Sinai School of Medicine.
The study suggests that age is a factor in estrogen treatment and sheds light on the intricate relationship between mind, age, and hormones. The study will be published in the online edition of Proceedings of the National Academy of Sciences during the week of June 25.
In a multi-center study comparing older rhesus monkeys with younger female monkeys, researchers found that estrogen significantly improved cognitive function in older animals but not in young monkeys. The study was led by Jiandong Hao, MD, PhD, Assistant Professor of Neuroscience, and senior co-author John H. Morrison, PhD, Dean of Basic Sciences and the Graduate School of Biological Sciences, and the W.T.C. Johnson Professor of Geriatrics and Adult Development (Neurobiology of Aging). Peter Rapp, PhD, Interim Chair of the Department of Neuroscience and Associate Professor of Neuroscience, and Geriatrics and Adult Development, led the behavioral phase of the study. Partrick Hof, MD, the Irving and Dorothy Regenstreif Research Professor Neuroscience, and William Janssen, a researcher in Neurobiology of Aging, also contributed to the research.
Working with colleagues from the University of Toronto and the University of California-Davis, Drs. Morrison, Rapp, and Hao compared the outcomes of four groups of female monkeys that were ovarectomized, which induced menopause: old monkeys that received estrogen, old monkeys that did not receive estrogen, young monkeys that received estrogen, and young monkeys that did not receive estrogen. The treated animals received pure estradiol injections every 21 days while being tested on a series of cognitive tasks over the course of more than two years.
Cognitive performance tests showed the older treated animals performed almost as well as the younger animals, whereas older untreated animals displayed dramatic cognitive decline. Surprisingly, the younger animals performed equally well with or without estrogen treatments. The aged animals had their ovaries removed around the time of perimenopausebefore the onset of full menopauseand began treatment within months of ovariectomy.
Microscopic studies conducted after the cognitive testing was completed revealed that in the prefrontal cortexa region of the brain associated with cognitive tasks that Dr. Rapp used to test the monkeys'the older estrogen-treated animals showed a greater density of synaptic spines'tentacle-like structures that link brain cells to one another and aid in brain cell communicationwhile the older untreated animals showed no such neuronal growth. These spines are critically important for learning and memory.
The findings indicate that the debate on the potential benefits of postmenopausal hormone therapy is not yet over, says Dr. Morrison.There's been a great deal of confusion as to whether estrogen helps or harms post-menopausal women, and our findings tell us is that there is a very critical window of opportunity in which estrogen therapy may be helpful.
Dr. Morrison notes that this critical window may be around the time of perimenopause, in which cyclical estrogen treatments as used in this study may be particularly effective in protecting the brain from age-related decline.