The time from when women have their first menstrual period to the time when they reach menopause corresponds to the most active inflammatory disease period in multiple sclerosis (MS), according to published research. “MS is more common in women than men, and the disease onset is often between ages 20 and 40, which corresponds with the reproductive age in women,” explains Burcu Zeydan, MD. “While women have more frequent MS relapses, men enter the progressive phase earlier in life. In addition to genetic and environmental factors, hormonal factors are also likely contributors to sex differences in MS.”

Comparing Menopause Timing & Type in Women With & Without MS

Dr. Zeydan and colleagues had a study published in Brain Communications that investigated the relationship between reproductive history of menarche, pregnancy, and menopause and the progressive disease course, which is the most important contributor of disability worsening in MS. “Our targets important clinical questions,” says Dr. Zeydan, “as these data may help clinicians provide a more tailored approach in their management of women with MS.”

For the study, survey data were analyzed from 137 postmenopausal women with MS seen at the Mayo Clinic and compared with records from 396 age-matched controls without MS. Menopause type was classified as natural or non-natural, the latter of which included women who entered menopause due to receipt of surgery, chemotherapy, or radiotherapy. Menopause at age 45 or younger was considered premature or early. Progressive MS was defined as an irreversible worsening of neurological symptoms due to MS that lasted for a year or longer.

Does MS Impact Menopause or Does Menopause Impact MS?

Menarche age and age at natural menopause were similar between women with and without MS. “However, women with MS had a lower number of pregnancies compared with the control group,” Dr. Zeydan says. “In addition, nulliparous women had progressive MS onset at an earlier age than females with one or more full-term pregnancies.”

The study also found that women who had menopause before age 46 had earlier progressive MS onset, according to Dr Zeydan (Figure). “Similarly, women who had never given birth had earlier progressive MS onset when compared with women who had one or more pregnancies,” she says. “This association was also dose-dependent—the higher the number of pregnancies, the later the progressive MS onset.”

According to Dr. Zeydan, the findings were unique in that the study team was able to demonstrate that MS does not impact menopause. “Instead, it appears to be the opposite,” says Dr. Zeydan. “We also showed that there is a relationship between reproductive history and the more disabling progressive phase of the disease in women with MS.”

Implications for Counseling Women With MS

Findings from the study are clinically relevant and have potential implications for counseling women with MS about reproductive health, Dr. Zeydan says. “Women with MS who are planning to defer a pregnancy decision may take into consideration that a higher number of pregnancies is beneficial in delaying progressive MS onset,” she says. “If possible, women should also avoid early menopause interventions, such as surgery, because this may help postpone progressive MS onset and prevent or limit disability worsening. Clinicians are encouraged to discuss these decisions with their patients based on their current disease phase and disease activity levels.”

Ultimately, the study sets the stage for a prospective clinical trial to verify if menopausal hormone therapies could play a role in delaying the onset of progressive MS in the setting of premature or early menopause. “While causality remains uncertain, the associations we identified favored the potential impact of sex hormones on the progressive disease course in MS,” Dr. Zeydan says. “A future argument may be made about the role of perimenopausal hormone therapies in delaying progressive MS onset. If patients are already on hormone therapies, our findings may provide another reason to encourage them to stay on treatment. That said, future clinical trials are required for definite recommendations.”

References

Zeydan B, Atkinson EJ, Weis DM. Reproductive history and progressive multiple sclerosis risk in women. Brain Commun. 2020;2(2):fcaa185. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772117/.

Tutuncu M, Tang J, Zeid NA, et al. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler. 2013;19(2):188-198.

Paz Soldán MM, Novotna M, Abou Zeid N, et al. Relapses and disability accumulation in progressive multiple sclerosis. Neurology. 2015;84(1):81-88.