The implications of the menopausal transition on neuromuscular function

October 16, 2023

MyAge funded Dr Jessica Piasecki to work with Dr Paul Ansdell and Dr Daniele Magistro on a ‘proof of concept’ study investigating how the menopausal transition may influence how our brain controls our muscles. Jessica explains more about the project.

What’s the problem you wanted to address? 

Females typically live longer than males but spend a greater proportion of their later life in poor health. This happens because the strength of our muscle declines with age, which makes falls more likely, and may eventually result in a lack of independence.  Older females are also more likely to get fractures from their falls, due to their loss of hormones through the menopause. It is thought this change in hormonal environment, through the menopause, could be one of the major factors responsible for the differences in health between older males and females 

The sex hormones that females have within their body, can cross from the blood stream into the brain and may influence the way our brain controls our muscles; these dramatically drop off through the menopause. Previous findings from the researchers involved in this study have shown that nerve signals to the muscles decline from middle to older age in females, but this was not observed in males of the same age.

It is important to understand these disproportionately worse effects in older females through research to then be able to overcome them and improve later life health.   

How did your research help solve this? 

The aims of our research project were to: 

1) Establish neuromuscular alterations across the menopause (pre, peri and post menopause,  with and without hormone replacement therapy (HRT)). 

2) Understand the contributing behavioural changes shown by females across the menopausal transition.  

What did you find out? 

  • The physical impact 

We collected neuromuscular data from 35 participants. Although much still needs to be analysed, our initial data indicate a reduction in excitability (the communication between nerve cells of the brain and spinal cord) within post-menopausal females compared to those pre-menopausal.  

With ongoing analyses, we hope to establish whether the menopause, particularly the loss of sex hormones, can influence the ability of the nervous system to adapt and respond to commands from the brain. We believe these limitations may influence the ability of females to produce muscle force and explain why older females may experience more frailty.

  • HRT medication in public health 

Through our initial data we were able to identify differences in neuroplasticity between pre- and post-menopausal females. Post-menopausal females demonstrate a ‘blunting’ of the ‘corticospinal adaptation.’ However, it is a possibility that this blunting is reduced with females who are taking hormone replacement therapy (HRT). Thus, our study will look at, with further analysis, whether the use of HRT medication could be a viable means to reduce the impact of the menopausal transition on neuromuscular deconditioning in older age. This, could lead to discoveries that allow older women to remain active and independent, delaying the onset of frailty and poor musculoskeletal health. However, much more data needs to be collected to confirm this finding. 

  • Understanding the menopause experience  

We have also spoken with a wider population of females who are currently going through the menopause. Some of the more commonly expressed symptoms were brain fog, fatigue, anxiety and depression. All of these were reported to influence daily behaviours. It is clear these females want to understand more about their symptoms and the ways in which they can possibly manage these.  

This research project has highlighted the significant influence that menopause has on our neuromuscular system and how limiting the experience can be for some people. We hope to continue to add to this data, providing further mechanistic insight and provide education on the wider implications of the menopause. 

  • Increasing awareness

Our patient and public involvement activities have demonstrated the ability to enhance knowledge in and around the workplace regarding the menopause. If the data collected from these events demonstrate a significant change in knowledge around the menopause, these events could be utilised later by other institutions as a validated tool. If we can provide more consistent education and improve the knowledge of the population surrounding this topic, it is more likely to improve general health at an earlier stage of life, before the more drastic changes occur to the musculoskeletal system, particularly those associated with the menopausal transition. This would support a healthier workforce, provide benefits to public health, reducing the cost for health care systems and the number of dependent older females.

What are the wider impacts from the project and how does the collaboration contribute to development of the MyAge Roadmap?  

  • Interdisciplinary working 

The MyAge roadmap seeks to bring together interdisciplinary researchers to investigate elements of muscle resilience across the life course, building toward future UKRI applications.  

This project has already led to a number of grant applications within the same interdisciplinary research team, continuing to build our knowledge and understanding of muscle resilience across the lifespan, particularly in relation to the menopause. Collectively these projects will provide insights into how these changes work within the body and the implications on neuromuscular functions, whilst also understanding the lived experiences and behaviours associated with this particular time in the female lifespan.  

This detail will be able to support tailored interventions, specific to females, to be designed to alleviate neuromuscular deconditioning in later life, and later, the higher levels of frailty already identified in females compared to males. These projects will contribute towards levelling of the sex-health-ageing paradox and allow females to live in better health throughout older age.  

Research and skill capacity building  

We will continue to seek further funding to support ongoing projects, developing the skills through additional PhD students and securing UKRI grants to conduct a specified intervention study, based on outcome of the projects currently being pursued.  This MyAge funding has helped support several junior researchers in their pursuit of grant income, widening our skill base and enabling us to establish an interdisciplinary research team. 

What next? 

Dr Jessica Piasecki has received further grant income from the Royal Society and The Society of Endocrinology with Dr Paul Ansdell and Dr Daniele Magistro as Co-Investigators. This grant will expand upon work funded by MyAge, to include age-matched males and include further muscle groups. Dr Paul Ansdell has also secured further funding as co-Principal Investigator from the Office for Veteran’s Affairs for a project titled ‘Determinants of Female Veteran Brain Health’. Early pilot data collected as part of the MyAge project was included in this application.  

The outline of this grant application would be to map the responsiveness to a resistance exercise training regime, designed for the improvement of neuromuscular function, in both males and females across the lifespan. This would be an important element of the overarching aim of this research that seeks to address and identify any differences in biological sexes to exercise. It will also identify the most critical periods within the lifespan of males and females that will be most responsive to interventions, ultimately contributing to the improved health of males and females in older age. Data generated from this intervention would allow us to discern which aspect of nervous system function limits adaptation at different stages of the male and female lifespan, permitting future therapeutic interventions to be tailored accordingly.