patient care perspectives

Women With Multiple Sclerosis and the Potential Impacts of Menopause

by Robert A. Bermel, MD, MBA


The interaction between sex hormones and inflammation is a potentially important factor in the occurrence of relapses in women with multiple sclerosis (MS). In the setting of premature or early menopause, it remains unclear whether menopausal hormone therapies may effectively delay the onset of progressive MS.

Expert Commentary

Robert A. Bermel, MD, MBA

Staff Neurologist
Mellen Center for Multiple Sclerosis
Cleveland Clinic
Cleveland, OH

“The impact of hormonal treatments, particularly estrogens, on MS has been a topic of intense study.”

Robert A. Bermel, MD, MBA

The issue of hormonal influence on MS is very important to women with MS, and we often field questions and try to provide as much information about this topic as we can throughout the patient’s life span. Menopause is associated with a reduction in MS disease activity, specific to inflammation. A topic of particular interest is whether the onset of menopause influences the progression of MS. The specific mechanisms themselves are not completely understood, but we would categorize them as degenerative mechanisms whereby the patient would experience a steady or slow accumulation of disability over time rather than an accumulation due to active inflammation in the form of relapse.

As noted above, patients with MS who are entering menopause tend to have a reduction in disease activity due to active inflammation; they may also have a small acceleration of the likelihood of progression. Historically, women in their childbearing years who develop MS are likely to have higher levels of disease activity, active inflammation, new lesions, and relapses. These active inflammation events usually occur more frequently in women with MS who are in their childbearing years compared with men. And the onset of progression, the degenerative mechanisms, tend to be more common in men and somewhat delayed in women. When women hit menopause, whether it is natural, surgical, or hormonal, they assume more male-like characteristics of their disease. So that means less active inflammation and a transition to male levels of risk factors for progression. Further, earlier menopause in women appears to have a detrimental association with long-term MS prognosis.

The impact of hormonal treatments, particularly estrogens, on MS has been a topic of intense study. Estrogens are somewhat protective against progressive MS-related disability. In that sense, estrogen has been investigated as a disease-modifying therapy in women with MS, with mixed results in clinical trials. There does not seem to be a single simple mechanism that we can attribute these findings to; it is likely more complicated, involving multiple mechanisms.

The question of whether a patient should start hormonal therapy in the setting of menopause must be viewed in a context beyond just MS. Factors such as individual risks for breast and ovarian cancers, heart disease, and osteoporosis, as well as MS disease activity and response to disease-modifying therapy, are all important considerations. The decision involves discussions with the patient’s multidisciplinary care team, including their primary care physician, OB-GYN, and neurologist. From a neurologist perspective, I think that there is currently insufficient evidence in favor of hormonal therapy in menopausal women with MS, so we do not strongly advocate for it.


Bove R, Healy BC, Secor E, et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015;4(1):18-24. doi:10.1016/j.msard.2014.11.009

Disanto G, Handel AE, Ramagopalan SV. Estrogen-vitamin D interaction in multiple sclerosis. Fertil Steril. 2011;95(1):e3-e4. doi:10.1016/j.fertnstert.2010.09.047

Maglione A, Rolla S, De Mercanti SF, Cutrupi S, Clerico M. The adaptive immune system in multiple sclerosis: an estrogen-mediated point of view. Cells. 2019;8(10):1280. doi:10.3390/cells8101280

Priyanka HP, Nair RS. Neuroimmunomodulation by estrogen in health and disease. AIMS Neurosci. 2020;7(4):401-417. doi:10.3934/Neuroscience.2020025

Zeydan B, Atkinson EJ, Weis DM, et al. Reproductive history and progressive multiple sclerosis risk in women. Brain Commun. 2020;2(2):fcaa185. doi:10.1093/braincomms/fcaa185

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