Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis

Abstract

Female gender and hormones have been associated with disease activity in multiple sclerosis (MS). We investigated age at menarche, use of oral contraceptives and pregnancy in relation to progression of disability in relapsing onset and progressive onset MS. We conducted a cross-sectional survey among individuals with MS, registered by the Flemish MS Society in Belgium. A time-to-event analysis and Cox proportional hazard regression were performed with time to Expanded Disability Status Score (EDSS) of 6 (requires a cane) as outcome measure. Hazard ratios for the time from onset and the time from birth were adjusted for age at onset and immunomodulatory treatment. Data on 973 women with definite MS were collected. In the relapsing onset group, women with at least two pregnancies had a reduced risk to reach EDSS 6 compared with nulliparous women. In the progressive onset group, later age at menarche was associated with a reduced risk to reach EDSS 6, whereas oral contraceptive use was associated with a higher risk of reaching EDSS 6. Our study corroborates the association of pregnancies with a reduced progression of disability in relapsing onset MS. In progressive onset MS, a slower progression was found in women with a later onset of menarche and a more rapid progression occurred when women reported the use of oral contraceptives.

Parity Associated with Long-Term Disease Progression in Women with Multiple Sclerosis

“…This suggests that pregnancy may have a different impact during the progressive phase of the disease. These results are in line with D'hooge et al [13] who also show an effect of parity in RRMS but not in the progressive onset types of MS. Previous studies have shown that pregnancy is beneficial for the short term in MS.…”

“…Our data is consistent with Runmarker et al [15] who were one of the first to report a long term benefit of parity on MS disease course. Positive long term effects of parity have also been reported by others, using EDSS 6.0 as the outcome measure [14,13]. However, other studies showed conflicting results, but follow-up periods tended to be inconsistent or too short (3 to 12 months postpartum) [21,22].…”

“…Some studies report a long term beneficial effect on MS disease course among women who had children compared to those who did not [12][13][14][15], but other studies do not [5,[16][17][18].…”

Sex Differences in Resting-State Functional Connectivity in Multiple Sclerosis

“…For example, male and female patients with MS have shown differences in the markers of autoimmune function, [8][9][10] and there has been extensive research on the effects of sex hormones on disease progression, particularly during and after pregnancy. 11,12 There is evidence that fluctuations in hormone levels can affect tissue damage in the brain 13 ; these observations have prompted research on the use of sex hormones as a treatment for MS. 14,15 It is unclear, however, whether there are sex differences in conventional MR imaging measures of disease status. One review concluded that sex does not appear to affect conventional MR imaging measures, 16 whereas other research has found increased gray matter atrophy and decreased development of T2-weighted lesions in men and increased white matter atrophy in women.…”

Hormone therapy use and physical quality of life in postmenopausal women with multiple sclerosis

“…Overall, estrogens have been implicated in both shifts in immunomodulation in MS as well as purported neuroprotective effects. 19 Oral contraceptives, in observational studies, have been reported to have protective, [20][21][22] neutral, 23,24 and negative effects on MS risk and course [25][26][27] ; of note, the composition (estrogen and/or progestogen) and dosing may have varied according to the relevant study epochs, with potentially differing effects on risk. In addition, treatment with estriol (an estrogen markedly elevated during pregnancy, and that at lower doses has been used as HT in Europe and Asia 28 ) for 24 months was recently reported to have beneficial effects on relapses and patientreported fatigue.…”