Estrogen therapy may protect the aging brain cells of post-menopausal women if it's given early enough, said a study released Monday that is likely to further stir the debate over hormone replacement therapy (HRT).
The study suggests that estrogen protects the neurons in the post-menopausal female brain from inevitable, age-related deterioration if it is given around the time of perimenopause - the period before menopause when production of the sex hormones estrogen and progesterone begins to ease off.
The findings indicate that the debate on the potential benefits of HRT is not over yet, said John Morrison, a professor in the department of neuroscience at the Mount Sinai School of Medicine in New York.
"There's been a great deal of confusion as to whether estrogen helps or harms post-menopausal women, and our findings tell us that there is a very critical window of opportunity in which estrogen therapy may be helpful," he said.
For their experiment, Morrison and a team of colleagues tested the effect of supplemental estrogen, or estradiol, on a group of four rhesus monkeys, whose menstrual cycle and menopause are similar to those of humans.
All of the monkeys had their ovaries removed to induce menopause. The researchers then divided them into four groups: two with young rhesus monkeys, two with older monkeys.
One cohort of each age group was given an estrogen shot every 21 days for a period of two years. The others did not get additional hormones of any kind.
On short-term memory tests, the younger animals performed equally well, regardless of whether they got estrogen or not, but it was an entirely different story in the older animals.
The older rhesus monkeys that got the estrogen boosters performed as well as the younger animals, whereas the older untreated monkeys displayed dramatic cognitive declines, the paper said.
Autopsies showed that the estrogen had affected the neurons in the pre-frontal cortex - a region of the brain associated with cognitive tasks. The treated monkeys had a higher density of synaptic spines than the untreated animals.
The spines link brain cells to one another, aiding brain cell communication, and are critically important for learning and memory, but typically decrease with age.
The researchers believe the estrogen treatment induces growth of new, more dynamic spines, which partially compensate for the effect of aging.
"We found that this increase in synaptic spines in the prefrontal cortex in the older estrogen-treated monkeys appears to have prevented age-related cognitive decline," said Morrison, lead author on the paper.
Morrison said the higher density of spines seen in the brains of the animals treated with hormones suggests that estrogen allows for greater neuroplasticity.
"The younger animals retain neural plasticity in the absence of estrogen," he said, "but what's happening with the older animals is this double hit of both age and estrogen decline.
The findings of this study suggest that the timing of any hormonal intervention may be important, and that there is a window of opportunity to preserve brain function before it has deteriorated too far.
"If the brain is too old, then age-related decline may be difficult to reverse," said Morrison. "However, our study suggests that if we jump before it's too late, we may possibly prevent memory loss."
Millions of women abandoned HRT after a 2002 study showed that combined estrogen and progestin could raise a women's risk for breast cancer, stroke and heart disease, but more recent research suggests it may have a role to play in women's health if it is taken early and for a limited period.
The study released Monday appears in the Proceedings of the National Academy of Sciences.