New research shows how menopause affects the brain, from memory to mood

You can’t remember where you left the car keys, there’s a name at the tip of your tongue, or you’ve lost your train of thought. The cognitive challenges that often come with midlife hormone changes can undermine women’s confidence.  We examine the latest research

Dr Lisa Mosconi says a new generation of hormone therapies are promising.

DRAMATIC hormone changes during perimenopause and menopause not only lead to hot flushes and sleep disturbances but to brain fatigue.

“Every organ in the body, including the brain, is controlled by hormones,” says Prof Mary Ryan, a consultant endocrinologist at the University of Limerick and the author of It’s Probably Your Hormones.

“When women’s hormone levels start fluctuating during perimenopause, it kickstarts changes to their brains and they can experience a whole range of different cognitive symptoms as a result.”

Dr Deirdre Lundy, head of Ireland’s first public menopause clinic in the National Maternity Hospital, regularly comes across patients who complain of these symptoms.

“They tell me that they have difficulty recalling words and misplacing items,” she says. “They have trouble concentrating and can even forget appointments and events.”

Collectively, these symptoms are commonly known as brain fog.

“Like everything to do with menopause,” says Lundy, “the severity of brain fog differs from woman to woman.”

“We know from research and from speaking with women anecdotally that some sail through perimenopause and menopause while others are seriously affected by the hormonal changes involved,” says Ryan.

Dr Lisa Mosconi, a neuroscientist and director of the Weill Cornell Women’s Brain Initiative in New York, has recently written a book about this topic.

The Menopause Brain is an overview of the most up-to-date information about how midlife hormone changes affect women’s brains.

Women can suffer from cognitive issues during this time because of how their brains respond to the main female hormone oestrogen.

“Our brains are loaded with oestrogen receptors,” says Mosconi.

“Oestrogen also has neuroprotective effects, and plays a role in maintaining blood flow and anti-inflammatory processes, while supporting brain energy levels and neurotransmitter activity.”

Dr Deirdre Lundy, head of Ireland’s first public menopause clinic in the National Maternity Hospital

When women hit perimenopause, which usually begins in their mid-40s, oestrogen levels start to decline.

“This means that their brain is forced to reset and rewire itself now that there is no longer as much oestrogen available,” says Ryan.

This process takes time, and the brain can experience glitches as it adjusts.

Mosconi says reduced oestrogen levels in the hippocampus, crucial for memory consolidation and learning, can affect recall and cognitive function, causing women to lose their train of thought. Other parts of the brain are affected too.

“The amygdala, which influences emotional response; the prefrontal cortex, which is involved in decision making, attention, and multitasking; and the brainstem, which includes structures that regulate sleep and wake cycles, are all affected when oestrogen levels falter too because they are not activated as consistently as they used to be,” Mosconi says.

“This may prompt changes in mood, reasoning, and sleep patterns.”

Even hot flushes are caused by disruptions to the brain.

“The hypothalamus [which regulates body temperature] contains a high concentration of oestrogen receptors and, when oestrogen starts fluctuating, it can fail to do this correctly,” Mosconi adds.

Dr Lisa Mosconi, neuroscientist and director of the Weill Cornell Women’s Brain Initiative in New York

Cognitive issues

Some women’s cognitive menopausal symptoms are so severe that they worry they are developing early-onset dementia.

“They begin to wonder if they are literally losing their minds,” Mosconi says.

Mosconi and her team at the Weill Cornell Women’s Brain Initiative are studying what happens in women’s brains during menopause and how brain changes might be related to cognitive issues.

One of their studies involved carrying out brain scans on 54 women before and after menopause, tracking how their brains burned glucose to make energy.

Pre-menopause, these scans found healthy, active, and energised brains. However, post-menopause — there was a 30% drop in energy levels.

“These are intense shifts in the female brain,” says Mosconi. “They could account for menopause fatigue and could also impact women’s cognitive performance. They validate what women have been saying for centuries: Menopause affects your brain.”

A study published last month was the first ever to measure oestrogen activity in the brain and track how women’s brains responded to fluctuating levels.

Contrary to the prevailing theory that oestrogen receptors in the brain began switching off during perimenopause, leaving women struggling with symptoms, it found that the opposite happened. The brain upgraded its oestrogen receptors to maximise whatever oestrogen was available.

According to Mosconi, this is a positive example of the brain adapting in response to falling oestrogen levels. It’s something women should take heart from, just as they should from the fact that they successfully navigated puberty and pregnancy — both of which are times when fluctuating oestrogen levels affect women’s brains.

Ryan agrees it can be helpful for women to acknowledge they have been through a similar process before. “Take puberty, for example,” she says. “The hormones released at this time trigger significant brain changes, particularly in the limbic system and prefrontal cortex, which are associated with emotions and decision making, respectively.

“These areas of the brain are reconfigured during puberty, which could explain why teenagers tend to be emotional and might not always make the best decisions.”

Mosconi refers to puberty as one of the ‘three Ps’, describing them as “pivotal stages in a woman’s life when significant hormonal shifts occur in relation to oestrogen in particular”.

Pregnancy is characterised by “another unique set of hormonal changes that impact the brain, with many women experiencing temporary cognitive adjustments that are often referred to as mommy brain,” says Mosconi.

Perimenopause is the third significant hormonal change. “If our brain adapted to the first two of the three Ps,” says Mosconi, “we can expect it to adapt to perimenopause and menopause too.”

Women can take steps to support their brains through this process and even optimise their brain health while doing so. “Hormone replacement therapy (HRT) helps some but not others,” says Lundy. “Oestrogen therapy has been shown to help some women to maintain cognitive function.”

Mosconi adds that non-hormonal options like some forms of antidepressant medication, a new drug Fexolinetant to treat hot flushes, cognitive behavioural therapy, clinical hypnosis, and lifestyle modifications can help to manage menopausal symptoms while also protecting brain function.

A new generation of hormone therapies known as selective oestrogen receptor modulators (Serms) offer hope to women too. Mosconi is particularly interested in PhytoSerm, a plant-based modulator that supplies oestrogen to the brain.

“It represents a promising new frontier in menopausal treatment, because it mimics the effects of oestrogen in the brain while blocking its effects in other parts of the body — so that it doesn’t increase the risk of breast, uterine, or endometrial cancer,” she says.

“Until now, women with a uterus have had to take oestrogen in combination with progesterone to minimise this risk.

“With PhytoSerm, they can take oestrogen on its own. We are hopeful that it will offer a new and safe option for managing women’s menopausal symptoms and we’re also testing whether it can lower women’s risk of Alzheimer’s.”

Ryan is looking forward to PhytoSerm being made available in Ireland. “We do have some Serms available here, with Evista being one of the most commonly prescribed to prevent bone loss,” she says. “It will be fantastic when the likes of PhytoSerm are offered, as they will offer women who have a history of breast cancer another option for managing menopausal symptoms.”

Prof Mary Ryan, consultant endocrinologist at the University of Limerick

Optimising health

While Mosconi is devoting her professional life to exploring what menopause does to women’s brains, in her personal life, she is preparing for the impact it could have on her own.

“I’m in my mid-40s and still have a regular menstrual cycle but I’m readying myself,” she says.

“I’m a firm believer in the foundational role of diet, exercise, sleep, and stress management in supporting overall health, so for now my focus is on optimising my health across those areas.”

When her oestrogen levels begin to decline, she hopes that menopause will be a positive experience that results in her brain being rewired so that it’s better able to deal with the challenges of life post-menopause.

“Our brains have such a remarkable ability to adapt that they can become even more interconnected after menopause,” she says.

“Women can emerge from this transition with greater emotional resilience. The stabilisation of their hormone levels can lead to better emotional regulation.”

Ryan is equally optimistic.

“Symptoms usually settle within two to seven years, and women then emerge on the other side with a newly rewired brain that might function better,” she says.

“Changes in the amygdala can make it less sensitive, which can result in postmenopausal women feeling less anxious. Not having a monthly menstrual cycle can also make a huge difference, as women no longer have to deal with the pain, mood swings, and erratic emotions. All of this explains why it’s common for women to report a greater sense of contentment after menopause.”

Every woman experiences menopause differently. According to Dr Deirdre Lundy, some women don’t seem to be affected by this hormonal transition, while others experience severe cognitive symptoms that can start in their early 40s and continue into their 50s or 60s. Women who experience medical or premature menopause tend to be among the worst affected.

Hormonal change

These lifestyle changes will help minimise the impact of menopausal symptoms:

• Maintain a healthy diet rich in fibre and omega-3 fatty acids, says Dr Lisa Mosconi.
• Regular physical activity. “It’s been shown time and time again to have a good effect on hot flashes, brain fog, mood, sleep and stress levels, which tend to increase with menopause,” says Mosconi.
• Good sleep hygiene is vital. Consistent bedtimes and wake-up times, keeping your bedroom dark and cool, avoiding alcohol and caffeine in the hours before bed and actively relaxing your body and mind all contribute to a good night’s sleep.
• Stress management techniques such as mindfulness and yoga can help. Stress hormones work in balance with sex hormones, so if your body is busy making stress hormones, it downregulates the production of other hormones, including oestrogen. You can prevent this by minimising the stress in your life.
• Lundy advises women to remain cognitively engaged in the world by continuing to learn new things as they age.
• Stopping smoking will improve overall health.
• Cut back on excessive alcohol intake.
• Maintain your social contacts. “Get out there and talk to your friends, colleagues and neighbours,” says Lundy. “And if you are struggling in any way, get help.”

While menopausal symptoms may be challenging, Mosconi wants women to know they are transient and can be managed with the right interventions.