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The study by Hawkins and McDonnell1 found that in multiple sclerosis, women were more likely than men to have a benign course and that young subjects had a more benign course than older subjects with multiple sclerosis. These findings prompt the question: Do postmenopausal women with multiple sclerosis on estrogen replacement therapy do better than those not taking such therapy? Axonal damage is now recognised to be an important determinant of disability in multiple sclerosis (reviewed in Scolding and Franklin2 and de Stefano et al 3) and myself and colleagues have recently reported more severe axon loss in crossed corticospinal tracts in the spinal cord in men than women who died with a diagnosis of multiple sclerosis.4 Estrogen has growth promoting effects on some neurons5 and thus may have the capacity to protect axons from damage in multiple sclerosis. It might be predicted that estrogen replacement therapy could have a beneficial effect on postmenopausal women with multiple sclerosis.
The authors reply:
We appreciate the observations of Esiri on our paper. The reasons for the more benign course experienced by both younger and female patients are unclear but the hormonal theory she outlines is interesting and certainly has merit.
It has previously been demonstrated that in experimental allergic encephalomyelitis the animal model of multiple sclerosis, estrogen therapy significantly reduces the severity of the disease compared with placebo treatment and it has further been postulated that this favourable response may be mediated by increased production of Th2 cytokines such as interleukin-10.1-1 More pertinent has been the findings on the effect of pregnancy on multiple sclerosis where relapse rate declines antenatally only to increase again during the first 3 months postpartum.1-2 Interestingly, relapse rates are at their lowest during the last trimester of pregnancy when estrogen levels are reaching their peak.
The hormonal theory and variation in estrogen levels with age might also help to explain the significant proportion of patients in our study who, after an initially benign course, subsequently slip into the secondary progressive phase and seem to deteriorate at a rate similar to those in the “non-benign” category. Unfortunately we are not placed to confirm whether early menopause is associated with a poorer prognosis or if those taking estrogen replacement therapy enjoy a better prognosis and this is clearly worthy of further study.
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