Menopause and MS – two profound topics that overlap in the lives of many women. Around 90% of all women with multiple sclerosis (MS) receive their diagnosis before menopause. This means that when hormonal changes begin, they have usually already been living with MS for many years – and suddenly their symptoms, energy levels, sleep, and cognitive performance shift.
In this episode, I speak with Dr. Riley Bove, Associate Professor of Neurology at the University of California, San Francisco (UCSF). Dr. Bove is an MS neurologist and clinician scientist who researches how menopause affects the brain, disease severity, and quality of life in women with MS. She explains the hormonal changes that occur during perimenopause, why the symptoms of MS and menopause overlap so much, and what this means for diagnosis, treatment, and everyday life.
She also discusses hormone replacement therapy (HRT), so-called bioidentical hormones, biomarkers such as neurofilament light chain (NfL), gaps in research—and very practical tips: When should I talk to my neurologist about menopause? What do I need to be aware of when it comes to hormone therapy? And why is it so important to use this phase of life as a health check-in?
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About Dr. Riley Bove
Dr. Riley Bove, Associate Professor of Neurology at UCSF: I’m a neurologist specialized in multiple sclerosis at the University of California, San Francisco, where I’ve been for about ten years. Before neurology, I trained in anthropology, focusing on women’s health in its broader social, cultural, medical and even evolutionary context. I’ve always been interested in how changing behaviours, cultures and health systems shape women’s health – and MS is a great example of how culture and medicine influence outcomes for women in particular.
What led Dr. Bove to study menopause and MS?
Dr. Riley Bove: One starting point for me was a landmark book by medical anthropologist Margaret Lock, who compared menopause in North America and Japan. She showed that women’s experiences – cultural, emotional, familial, individual – and even biological symptoms like hot flashes differ across cultures. That fascinated me.
When you then look at menopause in women with MS, another pattern appears: about 90 % of women with MS are diagnosed before menopause. So most of them enter perimenopause and postmenopause already living with MS. That raises big questions: What does it mean to live with both MS and menopause? How will MS change after menopause, in the postmenopausal years? Both phases – the transition and the years after – are really important for women with MS.
What hormonal changes occur during the menopausal transition, especially in perimenopause?
Dr. Riley Bove, Associate Professor of Neurology at UCSF: As the number of follicles in the ovary declines, a cascade of hormonal changes follows. Typically, progesterone levels start to decrease first. Then, in the late reproductive years and into perimenopause, estrogen levels become very variable – sometimes very high, sometimes very low.
Once there are no follicles left, estrogen production drops more consistently. Interestingly, we don’t usually diagnose perimenopause or menopause by measuring estrogen or progesterone directly, because they fluctuate so much. Instead, we look at FSH (follicle-stimulating hormone) – a hormone produced in the brain. As estrogen drops, the brain “steps on the gas” and raises FSH to try to stimulate the ovaries.
In perimenopause, FSH levels start to climb; in postmenopause, they remain elevated. In women who menstruate, we also look at the absence of periods over time. The transition can take several years, and the exact pattern varies from woman to woman. Overall, though, the picture is falling estrogen, falling progesterone and a rise in FSH.
Are all women affected in the same way, or are there big individual differences?
Dr. Riley Bove: There are major individual differences. Lifespan experiences – like smoking and other earlier-life exposures – can change both the timing of menopause and the way the transition feels.
When we think of classic menopausal symptoms, vasomotor symptoms come to mind first: hot flashes, night sweats, cold sweats. Some women breeze through menopause with very mild symptoms. Others are profoundly affected, with hot flashes day and night, severe sleep disruption and a big impact on daily functioning.
On top of that, many other symptoms can show up:
fatigue
mood changes like depression and irritability
joint pain and stiffness
frozen shoulder
bladder and bowel changes
decreased libido
For women with MS, this is especially tricky, because all of these are also typical MS symptoms. That’s where the overlap between MS and menopause becomes very real.
How well informed are doctors – including neurologists and gynecologists – about the impact of menopause on health?
Dr. Riley Bove: Until maybe three or four years ago, we had surprisingly little data and very little structured training. Large cohort studies often didn’t capture menopausal changes well.
Neurologists in particular were rarely trained in the “neurology of menopause”. Menopause was seen as a women’s quality-of-life issue, a gynecological topic – not a brain health issue. When I ask neurologists at conferences who has had even one hour of training on menopause and brain health, only a few hands go up.
The good news: interest is now exploding. We see more research on menopause and brain aging, more long-term epidemiological studies, more efforts to catch up on education. But still, many neurologists are not yet well equipped to distinguish clearly between perimenopause and postmenopause or to integrate a women-centered perspective into MS care.
Could you explain what bioidentical hormones are and how they differ from traditional hormone therapy?
Dr. Riley Bove: “Bioidentical hormones” is a term that isn’t standardized very well. The basic idea is that these substances mimic the hormones our bodies produce, often derived from plant sources and perceived as more “natural”.
However, there’s a lot of heterogeneity in formulations and testing standards. Compared to more traditional synthetic hormone products, it can be harder to know exactly what to expect in terms of dosing and effect. Many women are drawn to bioidentical hormones because they sound more natural, while clinicians sometimes find them challenging because of the lack of standardization.
What are the benefits and risks of hormone therapy for women with MS during or after menopause?
Dr. Riley Bove: First, it’s helpful to separate short-term benefits during the transition from possible long-term effects.
Major menopause societies agree that systemic menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms like hot flashes and night sweats. Systemic means estrogen given for the whole body, often combined with a progestogen if the woman has a uterus (to protect the uterine lining).
Short-term, systemic MHT can:
dramatically reduce hot flashes and night sweats
improve sleep
improve urogenital symptoms
support bone density
improve overall quality of life
We distinguish this from local vaginal estrogen, which mainly addresses vaginal dryness and local urogenital complaints and has very low systemic absorption.
For long-term risks and benefits, the Women’s Health Initiative (WHI) is key. It showed increased risks when hormone therapy was started in women in their 60s, leading to a general fear that HRT was “bad for everyone”. But when you look closely at women who started therapy within about five years of their final menstrual period – the so-called “window of opportunity” – you see another picture: lower risk of certain cancers, lower risk of heart disease, lower all-cause mortality and improved bone density. At the same time, there is a slightly increased risk of blood clots and stroke, which seems lower with transdermal estrogen (through the skin) compared to oral forms.
For women with MS, the risk–benefit profile is broadly similar to the general population, with a few extra points:
If mobility is very limited, the clotting risk may be higher, so transdermal estrogen is often preferred.
Hot flashes can worsen MS symptoms because heat can temporarily aggravate neurological symptoms – a phenomenon known as Uhthoff’s phenomenon (heat-induced worsening of existing neurological deficits). Reducing hot flashes may therefore help prevent symptomatic “pseudo-relapses” and improve daily functioning.
The big open question: Is estrogen truly neuroprotective in MS over the long term? Observational data suggest possible protection against cognitive decline and dementia, but we still lack long enough interventional trials to be sure.
When might it be too late to start hormone therapy?
Dr. Riley Bove: Current thinking focuses on that “window of opportunity”: roughly within the first five years after the final menstrual period, or somewhat earlier during late perimenopause.
The idea is that estrogen receptors in the body and brain are used to seeing estrogen regularly. Many years after menopause, they may have adapted to a low-estrogen environment. If you then “flood” the system with estrogen again, the risk of adverse effects appears higher. That’s why we try to keep systemic MHT to that earlier window, unless there are very specific individual reasons otherwise.
How does a hormonal IUD fit into this picture? Do women still notice menopause?
Dr. Riley Bove: A hormonal IUD usually releases a progestogen, not estrogen. It mainly acts on the uterine lining and doesn’t provide the systemic estrogen that we associate with menopausal symptom relief or long-term effects.
Women with hormonal IUDs often have very light or no bleeding, so you can’t rely on periods to tell where they are in the reproductive life cycle. If the ovaries are still present, they will still go through perimenopause and menopause – only without the clear signal of the final menstrual period.
In such cases, we assess menopause based on symptoms and FSH levels, similar to women who’ve had a hysterectomy (uterus removed) and don’t have periods either.
Based on your research: how does the menopausal transition affect disease progression in MS?
Dr. Riley Bove: Early on, we looked at the Expanded Disability Status Scale (EDSS). That’s a very coarse measure of disability and not very sensitive to subtle changes. Different groups saw different patterns, partly depending on how disabled women were when they entered menopause and how long they were followed.
To get a more precise picture, we moved to more granular measures: biomarkers and quantitative functional tests.
What changes did you observe in functional outcomes and biomarkers like neurofilament light chain?
Dr. Riley Bove: In our recent work, we looked at:
Neurofilament light chain (NfL) in blood – a biomarker of neuroaxonal injury and disability progression.
The MS Functional Composite (MSFC) – a combined functional outcome including a cognitive test, a dexterity test and a walking test.
For both NfL and MSFC, we saw that the slope of worsening becomes somewhat steeper after menopause than before. It’s not a dramatic cliff, but menopause appears to be an inflection point, where biological aging, reproductive aging and chronological aging converge and slightly accelerate brain aging.
What do we know about the potential protective role of sex hormones like estrogen in MS?
Dr. Riley Bove: Observational studies in the general population show that the timing and type of menopause leave a long-term trace on the brain. Women with earlier or abrupt menopause – for example after surgical removal of both ovaries – have a higher risk of cognitive decline, Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment.
This strongly suggests that ovarian hormones, including estrogen, play a protective role for brain health. In MS, we see hints in observational data that estrogens may support cognition and overall brain health. But we still lack large, long-term interventional trials in which women start hormone therapy around menopause and are followed for many years with detailed cognitive testing and imaging.
So the hypothesis is clear – estrogen might be neuroprotective – but we haven’t yet “asked the question properly” in trials designed to prove or disprove it.
What advice would you give to women with MS who are approaching or going through menopause?
Dr. Riley Bove: Even if we don’t yet know whether “doing everything right” in perimenopause will fully protect women later, we have the hypothesis – and it’s important that we try.
I usually start talking to women with MS by age 45. The median age of natural menopause in women with MS appears similar to the general population – around 51 years. Some will reach menopause earlier, some later. You may not be close to your final period yet, but you should be prepared.
My key messages:
Expect change without panicking. If you’ve been stable for years and suddenly symptoms worsen – more fatigue, sleep problems, hot flashes, mood changes – it might be perimenopause, not MS progression.
Don’t suffer in silence. If hot flashes are bothersome, they should be treated – with menopausal hormone therapy or with non-hormonal medications. There is even a newer non-hormonal drug that specifically targets hot flashes, as well as antidepressants and gabapentin, which can also help.
Use this time as a “midlife health checkpoint”. See your neurologist and primary care doctor a bit more frequently for a few years. Screen for depression, sleep problems, bladder and bowel issues, joint pain – and manage them proactively.
Think beyond MS alone. Pay attention to cardiovascular risk factors, thyroid health, cancer screening, gynecologic exams and social well-being. All of these comorbidities and social factors can influence MS progression.
What kind of lifestyle strategies might help – with or without hormone therapy?
Dr. Riley Bove: For vasomotor symptoms, several non-pharmacological approaches have been studied:
Acupuncture
Hypnosis
Nerve blocks
The evidence is still evolving, but some women find these helpful. There is also a strong focus on weight management, with a trend in the U.S. towards combining GLP-1 agonists (a class of medications for weight loss and diabetes) with hormone therapy in menopause – another area we still need to understand better in MS.
Equally important is well-regulated sleep. Good sleep makes people more resilient to daytime symptoms. Sometimes that means optimizing sleep hygiene, sometimes evaluating for sleep disorders, sometimes carefully using sleep medication.
And then there are practical day-to-day strategies:
Dressing in layers to manage hot/cold episodes.
Planning the most demanding physical or cognitive tasks earlier in the day.
Cooling strategies where needed, especially for MS-related sensitivity to heat.
What are the biggest research gaps in menopause and MS?
Dr. Riley Bove: Clinically, I think we already know a lot about perimenopause if we really listen to our patients. Many neurologists who have followed hundreds of women with MS through midlife hear the same themes repeatedly. We’ve also started to create practical care guidelines to help clinicians address these issues systematically.
The big research gaps are:
Cognition: How exactly does menopause affect cognitive function over the long term in women with MS?
Long-term trajectories: We need large, long-term cohorts that follow women beyond menopause, with good phenotyping, imaging and biomarkers.
Mechanisms and modifiable pathways: By which biological pathways does menopause influence brain health in MS – and how can we intervene?
Which developments would you most like to see in the next five years?
Dr. Riley Bove: I’d like to see us build robust cohorts of women with MS who are carefully followed through perimenopause and beyond. Ideally, these cohorts would include:
detailed cognitive testing
repeated biomarker measurements (like NfL)
imaging
and a subgroup of women with surgical menopause, because their menopause has a clearly defined onset and can be a kind of “natural experiment”.
With such data, we could finally ask – and answer – the key questions about cognition, biomarkers and long-term brain health in relation to menopause and MS.
What message would you like to share with patients, caregivers, clinicians and researchers?
Dr. Riley Bove: First, we must validate the patient experience. So many women report similar things: overlapping symptoms, worries about progression, concerns about cognition and quality of life. We need to listen carefully and take these concerns seriously.
Second, I’d like care teams to think collaboratively and comprehensively: neurologists, gynecologists, primary care providers, mental health professionals, rehabilitation specialists. Prevention, symptomatic treatment and holistic care are all key to wellness during perimenopause – and may also be very important for maintaining brain health in the long run.
How and where can people follow Dr. Bove’s research or get in touch?
Dr. Riley Bove: People are welcome to contact me by email via UCSF and to visit our lab website at bovelab.ucsf.edu. There, you can find more information about our research, publications and ongoing studies related to women’s health, menopause and MS.
Farewell
Dr. Riley Bove, Associate Professor of Neurology at UCSF: Thank you for highlighting this topic – it’s incredibly important for our patients. I hope our discussion encourages women with MS, their families and their care teams to talk more openly about menopause and to work together on comprehensive, brain-healthy care throughout midlife and beyond.
See you soon and try to make the best out of your life,
Nele
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