Menopause in women with multiple sclerosis: A systematic review

Aim: Sex hormones have been suggested to have neuroprotective effects in the natural history of multiple sclerosis (MS), particularly in animal studies. The aim of the present review was to retrieve and systematically synthesize the evidence on the effect of menopause and hormonal replacement treatment (HRT) on the course of MS. Methods: A systematic literature search was conducted in the databases MEDLINE (accessed through PubMed), Scopus, clinicaltrials.gov and Cochrane Controlled Register of Trials (CENTRAL). Eligible studies were all those that included women with MS and reported on at least one of the following: a) disability and MS relapse rate before and after menopause, b) serum sex hormone concentrations, c) sexual function, d) age at menopause onset. Effects of HRT on MS clinical outcomes were also assessed. Results: Of the 4,102 retrieved studies, 28 were included in the systematic review. Of these, one reported the age at menopause for both controls and women with MS and found no difference between the two groups. There was no difference in the rates of relapse before and after menopause (risk ratio 1.21, 95 % confidence interval 0.91-1.61, p=0.218). Two intervention studies reported beneficial effects of estrogen therapy on women with MS; however, the majority of women were premenopausal. Three studies addressed the issue of sexual dysfunction in women with MS, but information on hormonal parameters was limited. Conclusions: The age at menopause is not associated with the presence of MS. The evidence on a potential causal effect of estrogen depletion on disability is inconclusive; still, relapse rate seems not be associated with menopause. The effect of HRT on the natural course of the disease remains to be defined.