The association of menopausal hormone levels with progression-related biomarkers in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) progression coincides temporally with menopause. However, it remains unclear whether the changes in disease course are related to the changes in reproductive hormone concentrations. We assessed the association of menopausal hormonal levels with progression-related biomarkers of MS and evaluated the changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels during menopausal hormone therapy (MHT) in a prospective baseline-controlled design. METHODS: The baseline serum estradiol, follicle stimulating hormone, and luteinizing hormone levels were measured from menopausal women with MS (n = 16) and healthy controls (HC, n = 15). SNfL and sGFAP were measured by single-molecule array. The associations of hormone levels with sNfL and sGFAP, and with Expanded Disability Status Scale (EDSS) and lesion load and whole brain volumes (WBV) in MRI were analyzed with Spearman's rank correlation and age-adjusted linear regression model. Changes in sNfL and sGFAP during one-year treatment with estradiol hemihydrate combined with cyclic dydrogesterone were assessed with Wilcoxon Signed Ranks Test. RESULTS: In MS group, baseline estradiol had a positive correlation with WBV in MRI and an inverse correlation with lesion load, sNfL and sGFAP, but no correlation with EDSS. The associations of low estradiol with high sGFAP and low WBV were independent of age. During MHT, there was no significant change in sNfL and sGFAP levels in MS group while in HC, sGFAP slightly decreased at three months but returned to baseline at 12 months. CONCLUSION: Our preliminary findings suggest that low estradiol in menopausal women with MS has an age-independent association with more pronounced brain atrophy and higher sGFAP and thus advanced astrogliosis which could partially explain the more rapid progression of MS after menopause. One year of MHT did not alter the sGFAP or sNfL levels in women with MS.

Menopausal symptoms and hormone therapy in women with multiple sclerosis: A baseline-controlled study.

BACKGROUND: Depression, sleep disturbances, and cognitive difficulties impair the quality of life in people with multiple sclerosis (MS). Similar symptoms are also frequent during the menopausal transition. In clinical practice, it is important to consider the multifactorial causes of these overlapping symptoms and the potential benefits of menopausal hormone therapy (MHT). The objective of this study was to evaluate vasomotor symptoms (VMS), mood, sleep, and cognition of menopausal women with and without MS at baseline and during one year of MHT. METHODS: In this prospective baseline-controlled study, peri- and early postmenopausal participants with (n=14) and without (n=13) MS received MHT containing 1 or 2 mg of estradiol and cyclical 10 mg dydrogesterone for one year. VMS frequency, depressive symptoms (measured by Beck Depression Inventory), insomnia severity (Insomnia Severity Index), and cognitive performance (Paced Auditory Serial Addition Test; PASAT, Symbol Digit Modalities Test; SDMT) were evaluated at baseline and at 3 and 12 months of treatment. Differences in the outcome measures between groups at baseline were assessed using the Mann-Whitney U test. Changes during follow-up compared to baseline within groups were evaluated by Wilcoxon Signed Ranks Test. P < 0.05 was considered for statistical significance. MS activity was monitored by clinical assessment and brain MRI at baseline and at 12 months. RESULTS: Depressive symptoms were more common in MS group, while vasomotor and insomnia symptoms were equally common. During follow-up with MHT, VMS frequency decreased in both groups. Depressive symptoms decreased at 3 months (p = 0.031 with MS; p = 0.024 without MS) and the reduction was sustained at 12 months (p = 0.017; p = 0.042, respectively). Alleviation in insomnia symptoms was seen in participants without MS at 3 months (p = 0.029) and in those participants with MS suffering insomnia at baseline (p = 0.016 at 3 months; p = 0.047 at 12 months). Both groups improved their performance in PASAT, but no significant change was observed in SDMT. MS activity at baseline was mainly stable, and no increase in activity was detected during MHT. CONCLUSION: Improvements in vasomotor, depressive, and insomnia symptoms observed during one year of MHT are encouraging and suggest that larger placebo-controlled studies of MHT in women with MS are warranted. Cognitive implications were inconclusive because the findings in PASAT likely result from practice effect. MHT did not show any adverse effect on MS activity and increasing safety data will hopefully facilitate patient recruitment for future studies.