Research on rhesus monkeys at UC Davis suggests estrogen therapy may benefit post-menopausal women’s brain health, but the therapy remains controversial because of increased risks for cancer, blood clots and stroke.
The preliminary findings are part of an ongoing five-year study at the California National Primate Research Center at UC Davis where lead researcher John Morrison has been studying the effect of a form of estrogen called estradiol on 48 female rhesus macaque monkeys.
That research, now in its fourth year, has found that post-menopausal monkeys given estradiol experience less cognitive decline than those not given the therapy. The success of the therapy depends on the monkey’s age at the time the hormone is given.
The study’s initial results suggest the same effect may apply to post-menopausal women since female monkeys go through menopause similarly to humans and see similar declines in cognitive health with age.
In the study, the monkeys that didn’t receive estradiol therapy showed a 30 percent decline in cognitive function, Morrison said.
“Now there is reasonable data that there is a window of opportunity where the brain and body respond well to estradiol treatment,” Morrison said.
That therapy, however, brings possible risks.
A 15-year National Institutes of Health study, completed in 2006, found that 16,608 post-menopausal women who took a combination of estrogen plus progestin, one of the most widely used therapies at the time, had a 26 percent higher risk of developing breast cancer and a 41 percent increased risk for stroke.
That study found that timing was essential in the therapy’s effectiveness. Post-menopausal women who had gone through a hysterectomy and were given estrogen saw benefits such as lessened risk of bone fractures, but health risks such as thrombosis and stroke rose the older a woman was at the onset of therapy.
The combination therapy study was stopped because the increased risks outweighed the benefits, said Rowan Chlebowski, professor of medicine at the David Geffen School of Medicine at UCLA. Chlebowski said women in their 50s using estrogen may see benefits, but such therapy was detrimental in older women 70 and above. “It looks like both progestin and estrogen alone increased stroke and had an unfavorable effect on cognition,” Chlebowski said.
The UC Davis research looked at whether estradiol therapy alone, without progestin, can stop age-related cognitive declines particularly in brain synapses, which are the neural pathways responsible for memory and other cognitive functions.
Of special interest to Morrison was the health, density and size of spines in synapses that are responsible for learning and that degenerate with age.
The study also looks at whether estradiol therapy can delay or stop neurons from dying, which is a hallmark of Alzheimer’s disease. “The thought here is that preventing Alzheimer’s disease will require maintaining synaptic health with aging,” Morrison said.
The UC Davis findings are novel for suggesting that estradiol can protect women’s brain health and delay the onset and severity of Alzheimer’s. The research has also backed earlier findings that timing was a critical factor when administering hormone therapy.
“It’s clear that the relative advantages and risks of hormone therapy are dependent on a woman’s age and time passed since menopause,” Morrison said.
“In preclinical models, estrogen helps to maintain the vascular system, but once the vascular system gets kind of rigid, then the clotting effects of estrogen take over and then you are at risk for stroke,” Morrison said.
Morrison suggests that women consult with their physician on the best approach for estrogen therapy. “There is great variability in how women react to menopause, and the relative risk or benefit should be assessed for each woman,” she said.