Ovarian Removal at Mid-life
How Does it Affect Your Brain?
For years, scientists have been investigating the relationship between ovarian removal and brain health. Now, a growing body of research suggests that women who undergo this surgery before natural menopause may experience mild short-term cognitive issues, as well as increased risk of impairment and dementia later in life.
Experts emphasize that this information is essential for women considering the surgery for medical reasons, such as reducing their cancer risk.
WHILE MANY WOMEN WILL LIKELY STILL DECIDE TO UNDERGO THE PROCEDURE, UNDERSTANDING THE POTENTIAL IMPACTS CAN HELP THEM PREPARE FOR SIDE EFFECTS, EXPLORE POTENTIAL TREATMENTS, OR PLAN ON HAVING CLOSER MONITORING FOR EARLY SIGNS OF DEMENTIA.
“They might still choose the surgery, but at least they won’t be surprised afterwards – which many women tell us they are,” said Dr. Gillian Einstein, professor of psychology at the University of Toronto, and the Wilfred and Joyce Posluns Research Chair in Women’s Brain Health and Aging.
HORMONES & THE BRAIN
Scientists have long suspected there was a link between the hormonal shift of menopause and cognitive decline. Dr. Einstein wondered if the hormone estradiol, a form of estrogen released during a woman’s reproductive years, played a role in these changes.
To learn more, she began studying women with BRCA gene mutations who had undergone ovarian removal in their 30s and 40s. By focusing on this group, she was able to study the effects of hormonal changes alone, without other potential factors that contribute to memory loss, like natural aging and age-related health conditions.
“These women were having their ovaries removed early in life while they were young and healthy,” Dr. Einstein explained.
Dr. Einstein’s group has conducted studies including neurological testing, brain imaging, blood tests, and qualitative research and interviews. She and other researchers found that ovarian removal at mid-life or earlier was linked to both short- and long-term cognitive side effects.
THERE’S A LOT OF EVIDENCE NOW THAT OOPHORECTOMY, A SURGICAL PROCEDURE WHERE ONE OR BOTH OF YOUR OVARIES ARE REMOVED, BEFORE THE AGE OF NATURAL MENOPAUSE IS A RISK FACTOR FOR COGNITIVE DECLINE AS WELL AS OTHER PROBLEMS.
One study by Dr. Einstein’s team found that women with early ovarian removal had increased difficulty with associative memory, or the ability to connect different memories, such as matching a face with a name. Another study by her group found an increased risk of sleep disorders like insomnia and sleep apnea.
Long term, undergoing ovarian removal prior to the age of natural menopause is associated with an increased risk of Alzheimer’s disease (AD) and dementia in late life, she noted.
STUDYING THE IMPACTS OF EARLY MENOPAUSE
Menopause at any age triggers a drop in estrogen, as well as other hormones, like progesterone. When the ovaries are removed before the age of natural menopause, this hormonal change occurs earlier in a woman’s life than it would otherwise. These changes can affect the brain.
In animals, estrogen is known to affect the physiological process involved in memory formation called long-term potentiation, said neurologist Dr. Victor Henderson, Director of the Stanford Alzheimer’s Disease Research Center. Studies have also suggested it plays a role in neuronal survival or the development of neurological processes, and in modifying the synapses of nerve cells.
“All of these, one would think, could have an effect on cognition in humans,” he said.
But researchers are still working to understand the mechanisms that lead to changes in the brain, said Dr. Michelle Mielke, Chair of Epidemiology and Prevention at Wake Forest University School of Medicine.
She noted that there are many different pathologies in the brain that can cause dementia in older adults, including vascular dementia, or changes to the blood vessels; sticky proteins called amyloids that play a role in AD; and other neurodegenerative disorders.
Her team of scientists wanted to know if they could figure out which of these processes were involved in the type of cognitive decline associated with ovarian removal.
After finding no signs of abnormal amyloid buildup, the researchers then focused on studying changes to white matter, a kind of insulation in the brain that helps brain cells transmit information efficiently.
THEY FOUND THAT WOMEN WHO HAD UNDERGONE MID-LIFE OOPHORECTOMY, PARTICULARLY BEFORE AGE 40, HAD REDUCED WHITE MATTER INTEGRITY ACROSS MULTIPLE REGIONS OF THE BRAIN.
Dr. Mielke explained that these changes are a marker of vascular pathology in dementia.
“This would suggest, then, that it’s potentially working through a vascular mechanism,” she said.
REDUCING THE IMPACT OF COGNITIVE SIDE EFFECTS
Even with these potential side effects, experts agreed that for women considering oophorectomy for medical reasons, the benefits still likely outweigh potential risks.
Numerous studies have shown that the procedure is effective in reducing cancer risk for women with BRCA mutations. For women who have previously been treated for BRCA-associated cancers, it can reduce risk of recurrence.
WE ARE NOT SUGGESTING THAT YOU SHOULDN’T HAVE YOUR OVARIES REMOVED.
But by understanding potential side effects, women can make better decisions about their health, Dr. Mielke said. That might include undergoing closer monitoring for memory problems or early signs of dementia.
Or, knowing that there may be ties to vascular dementia, women with pre-existing cardiovascular risk factors might take extra precautions in managing those conditions, she said.
In addition, there’s value in knowing what to expect, Dr. Einstein noted. Women who experience cognitive changes may want to seek extra support, such as using memory aids, or learn compensating strategies to help them remember things throughout the day, she said.
WHAT ABOUT HRT?
While more research is needed, there is some evidence that hormone replacement therapy (HRT) may be beneficial for women who undergo ovarian removal before natural menopause, particularly before age 40.
“In terms of hormone replacement therapy, specifically estrogen, we don’t necessarily know whether that can be protective or not,” Dr. Mielke said.
IN GENERAL, UNLESS YOU’RE AT HIGH RISK FOR CANCER, THERE IS A STRONG SUGGESTION THAT YOU TRY AND TAKE HORMONE REPLACEMENT THERAPY, BECAUSE AT LEAST SOME OF THE SIDE EFFECTS OF MENOPAUSE MAY BE ALLEVIATED A BIT.
In one recent study, Dr. Einstein’s team found that estradiol therapy helped mitigate changes in spatial working memory – the type of memory that helps you remember where you parked your car. Notably, however, it didn’t improve verbal episodic memory (which involves things like remembering details in stories).
“We like to say that estradiol is important but not a silver bullet,” she said. Beyond hormones, “anything that’s good
for your heart is generally also good for your brain,” Dr. Einstein explained.
Exercise has proven heart and brain benefits for women in menopause.
Eating a heart healthy diet, staying mentally and socially engaged, and getting adequate, high-quality sleep can also benefit brain health, she said.
INSPIRED BY WOMEN’S LIVES
Dr. Einstein will continue to study how women can reduce the cognitive impacts of oophorectomy. Future research includes a study investigating the role of inflammation in this process and whether NSAIDs can reduce risk.
Her lab is also launching a study backed by Women’s Brain Health Initiative that will look at whether giving women piano lessons can help improve memory and cognition.
A third project will test women’s cognitive function before and after ovarian removal. It’s the first time this type of prospective study, the gold standard in scientific research, has been conducted in this population.
Dr. Einstein said that when she began working with women undergoing ovarian removal in their 30s and 40s, she was struck by the circumstances of their lives. The women in this group were actively working, raising children, maintaining marriages, and often caring for aging parents when they were suddenly faced with undergoing a life-changing surgery.
“They are very busy women, and this is a very big decision,” she said. Those women now inspire her to continue her research, she explained.
“All of this has continued to fuel my desire to conduct research and produce good data, so that women considering this procedure can go into it with fully informed consent.
Source: Mind Over Matter V20