Brain Remodeling During Menopause

Menopause, like a lot of hormonal-induced changes in a woman's life, gets a bad rap. (See also: pregnancy and every menstrual cycle ever.) There are the hot flashes, the decreased libido, the supposed forgetfulness and all-around diminished vitality that accompanies this middle-aged transition.

But is it all true?

"The biggest misconception of menopause is that it's awful," said Jenny Dai Biller, M.D., MPH, Department of OB-GYN, Santa Clara Valley Medical Center, California. "Some people think that menopause marks the end of a woman's sexual life. Both are untrue."

What is true about menopause is it's often misunderstood—and still widely under-researched—so here's what emerging studies have to say about what happens at a biological level in a woman's brain during menopause.

A new look at menopause

According to Laurie A. Kane, M.D., an endocrinologist at Providence Saint John's Health Center in Santa Monica, California, a large part of the renewed interest in what happens to a woman's brain during menopause is based on The Study of Women's Health Across the Nation (SWAN), a multi-site longitudinal, epidemiologic study of 3,000 women over the course of 15 years.

The study examined the physical, biological, psychological and social changes during the transitional period of a woman's middle years. Menopause, of course, is a huge part of that—technically speaking, menopause is defined as the final menstrual period—though, you won't actually know you're officially in menopause until you've gone at least 12 months without a period, so it's a retroactive diagnosis.

However, it's the time leading up to the "official" start of menopause that many of the "classic" symptoms of menopause actually occur. This lead-in, known as perimenopause or the menopause transition, is when the hormone levels change and begin to decline as the ovaries run out of eggs to release. That transition time usually takes about four years, but can last as long as 10, Biller said, with the average age of menopause typically occurring at 51.5 years in the U.S.

The physical symptoms of the menopause transition are well-documented and can include irregular periods, sleep disruption, hot flashes, joint pain, mood swings, irritability, depression, anxiety, night sweats, fatigue, vaginal dryness and decreased libido.

'I am very excited about the emerging evidence on how menopause impacts brain function...Neuroimaging studies will bring us closer to solving the mystery of menopause and brain function.'

Some women also report cognitive symptoms, such as forgetfulness or brain fog. However, symptoms are highly individual to each person and it hasn't always been clear what exactly is driving the physical and mental symptoms some may experience.

For instance, Kane pointed out while the symptoms of menopause have largely been attributed to hormone changes, sleep disruption alone could cause so-called menopause symptoms, such as irritability, mood changes and cognitive function interruption or forgetfulness.

"Sleep disruption alone, whether it's from hot flashes or just the dropping estrogen causing anxiety—the sleep isn't solid, restorative sleep, so the brain isn't going to function well the next day," she explained.

The newer studies, then, are focused on examining what's actually happening at a biological level, which could help shed light on what symptoms occur and why—as well as offer solutions if needed.

"I am very excited about the emerging evidence on how menopause impacts brain function," Biller said. "Although women going through menopausal transition often complain of mood symptoms and hot flashes, there has never been scientific evidence to explain these symptoms. Neuroimaging studies will bring us closer to solving the mystery of menopause and brain function."

Menopause, but make it scientific

What the research so far has shown is while significant hormonal changes do happen during the menopause transition that can impact the brain—primarily, a drop in both progesterone and estrogen—over time, most of those changes do stabilize.

For instance, estrogen decreases can impact memory and cognitive function, while progesterone is key in restorative sleep. However, a June 2021 study in Scientific Reports found biomarkers related to cognitive processing largely stabilized after menopause occurred, as did gray matter volume (again, related to cognitive function).

The study noted the specific brain mitochondria ATP production in the brain suggested there was an "adaptive compensatory process" occurring—or in other words, the brain compensated for the very real physical changes that occurred as a result of menopause.

"Slight, transient decline in cognitive function—'brain fog'—during menopausal transition can occur," Biller said, "But, this usually resolves after menopause."

Kane also explained the SWAN study demonstrated that while there are some clear changes with the drop in hormone levels in the brain, it also showed stabilization in other areas of the brain.

She pointed out this follows what some women might notice as they go through the menopause transition—namely, that symptoms such as sleep disruptions, hot flashes or mood changes can be more significant in the beginning of the transition, then taper off.

"Once you get to a new steady state, like with a lot of other conditions, things kind of even out," Kane said.

Menopause matters

According to Kane, studies that focus on the brain-level happenings of menopause and the menopause transition could offer more clear solutions for anyone whose symptoms may be disrupting their lives.

"About a third of women will seek out a provider for help with menopause and menopause-related symptoms," she noted, adding there is some lingering hesitancy surrounding hormonal replacement therapy based on older studies that found a small increase in heart disease and breast cancer in women who were placed on oral premarin and synthetic progestin, medroxyprogesterone acetate.

However, according to Kane, neither of those hormones are used anymore (they've been replaced by more natural synthetic hormones), and she is hopeful the new brain-based studies will help guide individualized treatment options that can align with what's actually happening in the brain—for instance, utilizing hormone replacement therapy in the beginning of the transition, when symptoms may be the most severe.

'I hope that we see more studies like this, so we can know more and understand which women really should be treated right now.'

"I think we need more of these studies and to see what can we do to benefit cognitive function by giving natural physiologic amounts of estrodial and progesterone [and] testosterone, DHEA and pregnenolone," she added. "I hope that we see more studies like this, so we can know more and understand which women really should be treated right now."

No matter what the future may hold for what's uncovered about the inner workings of menopause, Biller also pointed out it's a vital reinforcement of the fact that more research needs to be done on menopause.

"About 6,000 U.S. women reach menopause every day (more than 2 million per year)—and since the average age of menopause is 51 years, women will spend more than one-third of their lives after menopause," she said. "Menopause matters."