Menopause and MS: a resource for health professionals

In a recent podcast, Dr Francesca Bridge, a neurologist and researcher at Alfred Health and Monash University, explored the connection between menopause and Multiple Sclerosis (MS), shedding light on an area of research that remains relatively underexplored.

Multiple sclerosis is marked by gender disparities, with women being more commonly affected, at a notable three-to-one ratio compared to men.

The role of sex hormones in MS is an area of particular interest. Fluctuations in sex hormone levels can influence MS clinical course. During pregnancy, characterised by elevated estrogen and progesterone levels, inflammatory MS activity often decreases. Conversely, in the postpartum period, marked by reduced estrogen levels, there is often an increase in MS activity and an increased risk of relapse.

A critical yet overlooked area of research pertains to how menopause interacts with MS. Dr. Bridge highlighted the need to fill this knowledge gap, particularly because of the possible association between sex hormones levels and disease activity.

To better understand the nature and extent of the gap, Dr. Bridge and her team undertook an extensive literature review of existing research in this area, confirming a substantial lack of evidence regarding the effects of menopause and associated disease activity.

Menopause itself is a clinical diagnosis, characterized by symptoms that can vary among women. Common indicators include vasomotor symptoms such as hot flashes and night sweats, mood changes, cognitive alterations, and shifts in urinary and sexual function.

Medically, menopause is defined as 12 consecutive months without menstruation, a retrospective diagnosis that can only be confirmed after this period has passed. Diagnostically, menopause is predominantly a clinical diagnosis characterised by classical symptoms and menstrual history. Pathology testing for hormone testing can be supportive of the diagnosis and is helpful in specific circumstances, however, is not routinely required. Symptoms may begin even before menstruation ceases during the perimenopausal stage, which can last for an average of four to six years.

The hormones of interest in relation to MS disease activity include anti-Mullerian hormone (AMH), estrogen, and progesterone. AMH, produced by the ovaries' follicular cells, serves as a substitute marker in assessing ovarian reserve. It peaks in the late 20s and then gradually decreases, becoming nearly undetectable by around 50 to 51 years of age. This early decline in AMH levels makes it a valuable marker for tracking ovarian changes during the perimenopausal period, serving as one of the initial indicators that ovarian reserve is diminishing.

Hormones like estrogen and progesterone are thought to have neuroprotective properties. Research in other neurological conditions, such as Alzheimer's disease, suggests these hormones may offer neuroprotection by reducing the risk of neuroinflammation and neurodegeneration. However, the relationship between these hormones and MS clinical trajectory requires further research.

Small radiological studies suggest that menopausal women with MS may have fewer radiological inflammatory lesions. However, these studies also reveal a concerning trend of increased brain atrophy or loss of brain volume during this time, hinting at a transition from an inflammatory to a more neurodegenerative phase of the disease.

Clinical studies further note subtle yet significant shifts in women with MS disease activity during menopause. Some experience a decline in clinical disability measures despite the absence of clinical or radiological relapses, suggesting that changes in disease can occur over this transitional period.

The interplay between menopause, aging, and MS is complex. While aging likely plays a role in the risk of disease progression, there is also evidence to suggest that hormonal changes can exacerbate these effects. However, further research is needed to confirm how these factors interact.

Dr Bridge also found there was a lack understanding and evidence measuring the relationship between menopausal symptoms and MS symptoms. Measuring these menopausal and MS symptoms objectively is challenging due to the significant variation among individuals. Some women report worsened MS symptoms during menopause, while others experience minimal changes or even improvements.

The impact of Hormone Replacement Therapy (HRT) in women with MS was explored in a number of small studies with varying results. Dr Bridge emphasized that HRT is just one part of the toolkit for managing symptoms during menopause. While it may help some women, the decision to use HRT should be made in consultation with healthcare professionals.

Research into the relationship between menopause and MS is ongoing. Dr. Bridge's current work aims to distinguish the effects of menopause from those of aging. Through her research, Dr Bridge also hopes to empower women to address menopausal symptoms by raising awareness. She encourages women to initiate conversations about menopause with their neurologists or seek guidance from women's health specialists when needed. These conversations should encompass a range of issues, including lifestyle changes, non-pharmacological measures, and medication options including and beyond HRT. By breaking the silence and addressing menopause's unique challenges, women with MS can better navigate this phase in their lives.

Menopause and multiple sclerosis with researcher Dr Francesca Bridge

Dr. Francesca Bridge is a Multiple Sclerosis and Neuroimmunology Fellow at the Alfred Hospital and a PhD Candidate at Monash University.
Listen to the full podcast.