Throughout their lives, women experience important changes associated with their reproductive cycle. When living with multiple sclerosis (MS), they need to cope with their condition while adapting to these changes [1]. Addressing existing gaps in knowledge concerning women’s health might ease their journey. “How does MS affect the experience of menopause?”, “How does MS fatigue impact parenting strategies?”, “What are the most effective strategies for managing issues around sexual intimacy, including those related to low sexual desire, changes in physical function, and MS symptoms?” [1, p. 11]. Insights into these and many other enquiries can help alleviate the challenges that women with MS face every day.
For over 30 years, the International Advisory Committee on Clinical Trials in MS – sponsored by ECTRIMS and the US National Multiple Sclerosis Society (NMSS) – has offered perspective and guidance on priority topics to be addressed in clinical trials and clinical practice. Ruth Ann Marrie, Past Chair of the International Committee of Clinical Trials in MS and professor at the University of Manitoba, led the initiative aiming to set priorities in women’s health topics in MS. “After thorough discussions with the entire committee, we identified several topics concerning women’s health as the next critical issues to address. Our priorities were established through collaborative group discussions, followed by the formation of a working group. We conducted a scoping review to understand which topics had previously received attention in the literature and we realised that several topics had been overlooked. Most of the research focused on pregnancy, while very few studies focused on menopause or gynaecological cancer. Therefore, we intended to set priorities to fill some of those gaps,” said Professor Marrie.
The scoping review investigated 353 studies regarding women’s health conducted from 1980 to 2020 [2]. Over time, the number of studies addressing women’s health issues has increased significantly. In 1983, only one study on women’s health was conducted. By 2004, this number increased to 10. By 2020, the number of studies addressing women’s health issues reached 45. In total, over 509 topics were investigated during these years. More than one-third of them focused on pregnancy, with a particular attention given to relapses, pregnancy complications, and exposure to disease-modifying therapy (DMT). Foetal/neonatal outcomes and sexual dysfunction were respectively the second and the third more common topics. The most surprising gap in the literature was related to menopause, which was investigated in only 10 studies [2].
Mar Tintoré, President of ECTRIMS, professor at the University of Vic – Catalonia’s Central University, and clinical coordinator of neurology in the Neurology-Neuroimmunology Department at the MS Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital in Barcelona, told us in a recent interview that: “We are all aware that women’s health has not been a subject of extensive research until 5 to 6 years ago, and the consequences of this have been significant. For many years, women with MS who intended to become pregnant had only two options: either not to be treated or to be under-treated. Data on the safety of the baby were lacking. Therefore, many women had to decide either not to become mothers or to put themselves at risk. Fortunately, over the past years, there has been a remarkable change in this regard, as pregnancy has become a topic of research. As a result, we now have more data on how to proceed and manage pregnancy under treatment, even in cases of high disease activity. Now it is time to address other topics as well, also related to aging.”
The International Committee decided to establish priorities regarding the topics related to women’s health that need to be addressed. Professor Marrie told us, “What we deemed really important was to get input insofar as we could from people around the world living with MS. Therefore, we elaborated a 3-step global engagement process. First, we twice surveyed various stakeholders – people with MS, caregivers, clinicians, researchers, and patient advocacy organisations – to identify which broad research topics relevant to women’s health in MS we should focus on with highest priority. We short-listed 6 topics. Second, we developed specific questions within focus groups. Then, the MS International Federation (MSIF) was kind enough to let me present our work on their International Medical Scientific Board (IMSB). We formed focus groups with them as well, and this enabled us to generate a long list of questions. We prioritised the research questions using a third survey. At the end, this process has given us important topics to work on”.
The two large initial surveys included over 5,000 respondents, who identified menopause, sexual dysfunction, pregnancy, gynaecologic cancer/cancer screening, hormones, and parenthood as the priority topics of interest for future research [1]. After the identification of the priority research topics, members of the MSIF IMSB suggested relevant questions for each topic. The questions were later discussed in focus groups with participants drawn from the respondents to the global survey.
The focus groups
Marcia Finlayson, professor at Queen’s University, was invited to lead the focus groups with a semi-structured interview guide, which included open-ended questions to explore during the session. “Focus groups are interesting because they allow people to share similar experiences and learn from each other. Moreover, in the process of having a discussion, they build on each other’s ideas. This results in a rich, fulsome, and comprehensive perspective on a particular issue or concern. I remember a discussion about menopause. People were describing their symptoms and experiences, but they were struggling to figure out how MS was affecting their experience of menopause. One would hear questions such as, ‘Is this my MS or is it a menopausal symptom?’, or ‘Is my menopausal symptom making my MS worse?’. I hope that we will have soon special research calls for some of the topic questions. All of us want to enable people with MS to have quality of life and live well with MS. Maybe studying some of these topics will enable that to happen,” explained Professor Finlayson.
Dr. Lindsay Ross, neurologist at the Cleveland Clinic, is the first author of the study. She told us, “It impressed me to see how open and honest people were willing to be about sharing their experiences. Moreover, it was really eye opening to look at things from the other side, from the perspective of the patients. As clinicians taking care of individuals with MS, we often talk with our patients about fatigue. However, in the focus groups we could learn from the patients how they really experience fatigue in their daily life. The people in the focus groups highlighted aspects that we would have perhaps not thought of. I remember that many persons with MS and their caregivers mentioned being referred to pelvic floor physical therapy, but only a few of them were prepared for what it would be like. They were honest in sharing their surprise and fear. This experience will certainly enrich my clinical practice. Beyond that, we see concerted efforts from patients, founders, and researchers to advance our understanding of women’s health issues of persons with MS. I think we will closely monitor how the field will respond to this work and see where that can go.”
Resolving uncertainty by addressing the priority topics
“The results of this study – mainly driven by the patients and their caregivers – were extremely logical and powerful,” commented Professor Tintoré. “Worldwide, the population is living longer than ever before and is aging. All the topics related to aging, including menopause, are becoming more and more relevant. While our understanding of pregnancy has improved, there are still many uncertainties surrounding menopause and various other women’s health issue. Also, the second selected topic – women’s sexual dysfunction – is worth our attention. We know very little about sexual dysfunction in MS. The parenting topic is very interesting as well. This is something that patients tell us a lot. Mothers of small children sometimes receive complaints, ‘Mom, you are always tired!’. It is challenging for a mother with MS because the fatigue cannot be seen from the outside and this can create difficulties in personal relationships. We need to address these priority topics and engage people with MS and caregivers in our studies.”
Professor Marrie added: “We identified a specific set of priorities in women’s health topics in MS, ensuring that the voice of people with MS contributed to determine these priorities. The results highlighted how much MS can impact all facets of women’s lives and how we really need to think of this in our discussions about symptom management and disease modifying therapies. We must think about how to tailor the management of those issues, asking more specific kind of questions, and providing people with resources and appropriate guidance. Even people who do not have MS may face many challenges associated to the priority topics that we identified. For example, women with menopause can experience hot flashes, lack of sleep, more fatigue, troubles with brain fog, and body aches. These are common experiences in women with MS. What happens then during menopause? Do these symptoms get worse? Does the MS-related fatigue exacerbate if someone starts having trouble sleeping? These and many other questions need answers. This uncertainty must be solved as soon as possible. I hope that our initiative will encourage researchers to investigate these questions in a timely fashion, and that funders will be willing to support research targeting these priorities. This will enable us to better manage these issues and to help patients take decisions and live a better life.”
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Written by Stefania de Vito
Special thanks to Prof. Ruth Ann Marrie (University of Manitoba), Prof. Mar Tintoré (President of ECTRIMS; Cemcat), Prof. Marcia Finlayson (Queen’s University), and Dr. Lindsay Ross (Cleveland Clinic), for their insights.
References
[1] Ross L et al. Front. Neurol. 2024; 15, 1355817.
[2] Ross L et al. Front. Neurol. 2022; 12: 812147.