Menopause is a natural phase in a woman’s reproductive cycle, characterised by the permanent cessation of ovarian activity [1]. This transition leads to significant physiological changes, including hormonal fluctuations, which can cause vasomotor symptoms like hot flashes and night sweats, sleep difficulties, and urinary and sexual dysfunctions [2]. Many women with multiple sclerosis (MS) experience the transition to menopause while managing their MS [3], and in some cases, menopause can exacerbate their MS symptoms [4]. Despite this, very few studies have investigated the impact of menopause on MS [5]. To address this research gap, the International Advisory Committee on Clinical Trials in MS – sponsored by ECTRIMS and the US National MS Society – has recently identified menopause as a priority topic for future research on women’s health [6].
MS and menopause: two worlds that overlap and interact
The overlap between menopause and MS symptoms can be challenging for women with MS and healthcare providers. MS is a continuum where both inflammation and neurodegeneration are present from the onset. However, as ageing advances, the neurodegenerative component becomes increasingly prominent [7]. Therefore, it can be unclear whether some symptoms are due to a change of the course of MS or rather to menopause [8].
Professor Kerstin Hellwig, from the Ruhr University of Bochum in Germany, shares her perspective with us, “In my experience as a neurologist, I have observed that women with or without MS rarely directly complain about menopause. Instead, they often mention symptoms indirectly related to menopause, such as depression, cognitive decline, and fatigue. Disentangling the substantial changes associated with the transition to menopause from MS symptoms is challenging. We need to be ready to recognise these symptoms and refer our patients to gynecologists for further evaluation”.
Professor Riley Bove, from the University of California, San Francisco (UCSF), also emphasises the need for an interdisciplinary approach, “The two worlds of menopause and MS interact. Therefore, there is a need for a comprehensive approach to clinical management. It is not just about menopause or just about MS, but rather their interplay that requires attention. The menopausal transition varies greatly from person to person, with experiences being highly personal and different from one another. While some women go through it smoothly, others may require support”.
“In my clinical practice”, Professor Bove continues, “women with MS approaching menopause often express their concerns, saying verbatim, « I don’t know if it is my MS, my menopause, or both ». Symptoms can overlap and, in some cases, interact. For example, the heat from hot flashes during menopause can exacerbate preexisting MS symptoms. Mild sleep difficulties may worsen due to hot flashes, leading to increased daytime fatigue. This creates a vicious cycle. Due to intensified sleep difficulties, cognitive problems, and fatigue, some women may fear they are developing another condition alongside MS. They may wonder, « Do I have Alzheimer’s disease now? ». Some women with both MS and menopause may feel extremely tired and depleted. They can be overwhelmed and say, « I can’t take it anymore ». Balancing family and work responsibilities, they might find they need more time for self-care and additional interventions. This could entail taking afternoon naps or even requesting a part-time schedule at work”.
Managing menopause in women with MS
Some women with MS who go through menopause may need to alleviate their vasomotor symptoms. Hot flashes and night sweats can lead to a Uhthoff’s-like phenomenon – a temporary decline in neurological function and exacerbation of MS symptoms [2]. Additionally, menopausal women with MS may see a worsening of disability, possibly due to declining levels of hormones like anti-Müllerian hormone, and estrogens [9]. Professor Hellwig notes, “Women with MS often suffer from fatigue, cognitive disorders, anxiety, or depression, which are also common menopausal symptoms. Lower levels of anti-Müllerian hormone, a marker of ovarian ageing, are associated with greater disability and decreased gray matter in women with MS. This association does not depend on age or disease duration [10]. The impact of menopause on MS remains an unresolved question”.
In the general population, hormone therapy (HT) can help mitigate menopausal symptoms and preserve bone density [11]. However, there is insufficient data on the safety and efficacy of HT in women with MS. For some women, there may be contraindications to the use of HT, such as an increased risk of thromboembolic events [11]. Other pharmacological options include non-hormonal treatments, such as medications that can help regulate mood and relieve depression – selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) [12].
Lifestyle changes and early screenings
Given the insufficient data on treatments for menopausal symptoms in women with MS, we sought Professor Bove’s opinion on behavioral approaches that could aid in the transition to menopause. It is important to note that these approaches currently lack a robust evidence base, highlighting the need for more research in this field.
Professor Bove suggests behavioral approaches that might help women living both MS and menopause feel better, “It is important to frame the menopause transition as a window of opportunity to treat symptoms and improve quality of life. Highlighting the contribution of lifestyle to mental health is crucial. Lifestyle changes are not a luxury but a recipe for well-being. We understand that vasomotor symptoms can sometimes trigger a domino effect, impacting sleep quality, mood, and overall functioning. Therefore, individuals can take steps to manage these symptoms by dressing in layers, maintaining a cool room at night, practicing yoga, using cool packs, and considering cooling vests. We strongly advise to prioritise social connections, spend time with friends and partners, ensure adequate sleep, follow a Mediterranean diet, engage in regular walks and exercise to build muscle mass, and bone strength, and consider psychotherapy. These resources can contribute to overall well-being. Other than that, early screenings in view of the menopausal transition are also recommended, including cardiometabolic testing, cancer screenings, cholesterol and diabetes checks, and assessment of bone mineral density. It is also crucial to ensure that individuals are up to date with all age-related vaccines and receive the necessary booster shots”.
The North American Menopause Society (NAMS) highlights osteoporosis as a health threat for women who reach menopause. With osteoporosis, bones weaken, become fragile and more susceptible to fractures. A good diet, regular physical activity, smoking cessation, and a reduction of alcohol consumption are recommended to improve bone health [13]. For women with significant risks factors for fracture, behavioral approaches can be combined with pharmacological treatments and strategies to prevent fall risk [13]. Additionally, optimising sleep quality, stabilising mood, and reducing hot flashes and their interference in daily life can enhance mental health [2]. For women with MS, complementary modalities may be necessary. The impact and the combination of disease-modifying therapies, symptomatic therapies, lifestyle changes, and rehabilitation should be further investigated, considering important obstacles that can hinder the feasibility of clinical trials [11]. In a recent clinical trial, enrollment was protracted for almost three years, with only one woman recruited per month. Many women declined to participate, expressing main concerns about the safety of hormone therapy [11]. Sharing updated and personalised information about treatment safety can be a good strategy to encourage more women with MS to participate [11].
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Written by Stefania de Vito
Special thanks to Professor Riley Bove (University of California, San Francisco) and to Professor Kerstin Hellwig (Ruhr University Bochum) for their insights.
References
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