Women with multiple sclerosis (MS) who had never given birth and those who began menopause prematurely developed progressive MS earlier, a single-center observational analysis suggested.
Nulliparous women experienced progressive MS onset at a mean age of 41.9, while women with one or more full-term pregnancies had progressive MS onset at a mean age of 47.1 (P=0.069), reported Burcu Zeydan, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.
Pregnancies appeared to have a dose effect on delaying progressive MS onset. Women with a history of one to three full pregnancies had progressive MS at a mean age of 46.4, while those with four or more pregnancies had progressive MS at a mean age of 52.6 (P=0.005).
Menopause age also was associated with progressive MS onset age (R2=0.359, P<0.001), Zeydan and colleagues wrote in Brain Communications.
The study explores the intricate relationship between sex hormones and MS, Zeydan said. “It is unique because it demonstrates that MS does not impact menopause, but potentially vice versa,” she told MedPage Today.
The findings have potential implications for counseling women with MS about reproductive health, Zeydan added. “For example, women with MS who are questioning a pregnancy decision may now consider that a higher number of pregnancies are actually associated with a delay in progressive MS onset,” she said. “Similarly, prevention of early menopause, such as avoiding oophorectomy, may help delay progressive MS onset and prevent long-term disability accumulation.”
Numerous reports, including a 1998 prospective study, have shown that women have a reduced risk of relapse during pregnancy followed by an increased risk of disease reactivation after delivery. How MS is related to longer-term outcomes like disease progression is less clear, however.
In this analysis, Zeydan and colleagues looked at survey data from 137 postmenopausal MS patients seen at the Mayo Clinic, and records of 396 age-matched controls without MS, from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2, a population-based cohort in Olmsted, Minnesota. MS patients were a median age of 62.6, and survey data were cross-checked against Mayo Clinic medical records.
Menopause type was classified as natural or non-natural, which included women who went into menopause due to surgical intervention or chemotherapy/radiotherapy. Menopause at age 45 or younger was considered premature/early. Progressive MS was defined as an insidious, irreversible worsening of neurological symptoms due to MS lasting for 1 year or more.
Menarche age was similar between MS patients and controls (P=0.306). Women with MS had fewer full-term pregnancies than the controls (P<0.001). Non-natural menopause was more common in MS patients (40.7%) than in controls (30.1%, P=0.030). Median age at natural menopause was similar between groups (age 50 for MS patients; 51 for controls).
Time from onset of MS relapses to onset of progressive MS was shorter for women with premature/early menopause (mean 12.9 years) than for women with normal menopause (mean 17.8 years). Age at menopause also was associated with age at reaching severe disability, defined as an Expanded Disability Status Scale (EDSS) score of 6 (R2=0.229, P<0.003).
The researchers also saw a pregnancy-dose relationship with the age that women reached EDSS 6. Women who had never given birth reached EDSS-6 at age 43. Women with one to three full pregnancies reached EDSS-6 at age 51.7, and women with four or more pregnancies reached EDSS- 6 at age 53.5 (P=0.013).
The study had several limitations. The clinical series of patients from which the survey respondents were drawn was enriched for progressive MS and for older patients. Patients and controls may not represent women outside the Mayo Clinic groups. Modern disease-modifying therapies also may affect findings, since the study group consisted of older patients who would have not received immunomodulation early in their disease course, Zeydan and colleagues noted.
The study was supported by the NIH. Controls were from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2, made possible by the Rochester Epidemiology Project.
Researchers disclosed relevant relationships with Biogen, RSR, MedImmune, Alexion, Caladrius Biosciences, Brainstorm Therapeutics, Novartis, Takeda, Avid Radiopharmaceuticals, and Eli Lilly.