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Although there is sufficient knowledge speculating the unique and potentially debilitating side effects associated with multiple sclerosis, little attention is focused on the MS symptoms that exclusively affect women. Comprising the vast majority of patients living with MS, it is crucial to underscore the importance of understanding and managing these symptoms within the MS community. According to recent research, women are approximately four times more likely to be diagnosed with MS compared to their male counterparts. With this in mind, it is encouraging to see studies devoted to women’s health issues as they relate to MS continue to emerge. 

As both an autoimmune and neurodegenerative disease, MS can present in a variety of ways, with an extensive list of symptoms. Many of these symptoms – such as numbness, tingling, fatigue, weakness, and vision problems – are commonly recognized as they present in most patients irrespective of gender. Receiving much less attention are the symptoms specific to women, such as menstrual problems, menopausal issues, and pregnancy-related concerns. As most women receive their MS diagnosis between the ages of 20-40, all three of these health concerns become issues for many women living with MS. Menopause specifically has been shown to synchronously worsen as MS progresses in some women. With menopause typically lasting five to seven years in the majority of women in the United States, the compounded effects of MS can pose a relatively long-term hardship for hundreds of thousands of women.

Menopause commences as a result of hormonal changes that occur as women enter their late 40s and into their early 50s. Up to this pivotal point, the ovaries produce healthy levels of estrogen, progesterone, and testosterone (the main steroid hormones) that contribute to the cyclic menstruation patterns women experience from puberty to about 37 years old. As women age, the ovarian cells deteriorate and estradiol, a form of estrogen, consequentially declines. Menstrual irregularity is typically the first sign of menopause, but some of the cardinal signs and symptoms also include hot flashes, night sweats, urogenital issues, sleep disruption, and cognitive impairments including memory loss. Although these symptoms can affect all women, studies have shown that women with MS experience more severe symptoms after menopause, presumably due to a loss of estrogen. Assuming estrogen regression is the culprit, hormone replacement therapy is being studied in women with MS to evaluate its efficacy in mitigating symptom exacerbation. 

Estriol, a weaker estrogen, surges during pregnancy and acts as an estrogen receptor agonist. Women with MS have been known to go into remission during pregnancy, in part because of hormone fluctuations. Estriol is employed in a similar manner as hormone replacement therapy for women experiencing menopause to improve their quality of life. Studies are beginning to show a link between steroid hormones and the process of myelination, which is damaged during the course of MS. Furthermore, estriol possesses immunomodulatory effects as it reduces proinflammatory cytokines that contribute to some MS symptoms. Although utilized in other countries, estriol is not yet FDA approved in the U.S. for prescription use.

A pilot study conducted in London evaluated the effects of estrogen hormone replacement therapy in patients with MS who are going through menopause. The researchers distributed questionnaires to participants which described changes in the severity of MS symptoms. Of the 19 postmenopausal women who participated, about half concurrently took hormone replacement therapy in combination with their disease modifying agents. The questionnaires revealed these women reported 75 percent improvement in their disability compared to 8 percent improvement in the group without hormone replacement therapy. The American Academy of Neurology published a slightly larger study in which 95 postmenopausal women with MS completed a physical function test to evaluate their quality of life. Out of the 95 participants, 61 women had been using hormone replacement therapy (systemic estrogen with or without progestin) for at least 12 months. This study found that the women who used hormone replacement therapy had physical function scores (PF10 scores) that were, on average, 23 points higher than to nonhormone replacement therapy users. Researchers also noted that women who had been on hormone replacement therapy for longer periods of time translated to higher PF10 scores. A third study out of Brigham and Women’s Hospital explored the evolution of disability after menopause in women with MS and suggested a potential protective effect from initiating hormonal therapies in perimenopausal women with MS. 

Although the results discussed in these studies are encouraging as to the potential benefits of hormone replacement therapy in menopausal and postmenopausal women with MS, there is a lack of representation in many studies dedicated to confirming this relationship. That being said, more studies are warranted in the future to evaluate this theory on a larger scale. Of equal concern is the risk versus benefit of initiating hormone replacement therapy as there are associated health concerns that may make these therapies unsafe in some women. Patients should always discuss new therapy options with their primary care doctor and neurologist to ensure there are no contraindications to hormone supplementation. 

As we progress with an aging population, it is imperative to focus attention on women with MS who will likely live at least a third of their lives after menopause. Most therapeutic options in the MS world are disease modifying agents with little attention dedicated to symptom management. Even less attention is devoted to women’s health issues regardless of the fact that MS disproportionately affects women year after year. Although many studies show promising results of hormone replacement therapy utilization in women with MS during their menopausal years, further exploration is needed to substantiate these findings. 

-- Savannah Gross is a doctor of pharmacy candidate at the University of Georgia.