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Research suggests that hormones influence the duration and severity of autoimmunity affecting the CNS. One study found abnormally low levels of testosterone in human males with MS, and animal models of MS have shown low levels of testosterone and increased levels of luteinizing hormone,54 as well as an inverse relationship between testosterone levels and levels of inflammatory mediators.54 Another study showed improvement in cognitive performance, a slowing of brain atrophy, and increased lean body mass upon supplementation with a gel containing 100 mg of testosterone given daily to men with relapsing-remitting MS for a 12-month period.55 However, the supplementation had no significant effect on the numbers or volumes of sclerotic lesions.55 Levels of the androgen dehydroepiandrosterone (DHEA) have also been found to be significantly lower in MS patients than in healthy individuals.56

Estrogen levels also appear to play a role in the severity of MS symptoms. Among a group of menopausal women with MS, 82% reported premenstrually increased symptom severity, 54% reported a worsening of symptoms with menopause, and 75% of those who had tried hormone replacement therapy reported an improvement in symptoms.57 Studies indicate that low-dose estradiol may be beneficial for women with MS. Animal models show that low-dose estradiol inhibits T-cell migration into the CNS and has neuroprotective effects that promote axon and myelin survival.58 Estrogens have also been found to inhibit the production of proinflammatory Th1 cytokines such as IL-12, TNF-alpha, and IFN gamma, and to stimulate the production of anti-inflammatory Th2 cytokines such as IL-10, IL-4, and TGF-beta. This may explain why estrogen modulates Th1- and Th2-mediated diseases such as MS.59 Studies of pregnancy in women with MS also suggest a role of hormones in the disease. Of the women studied, 75% showed a distinct shift from a Th2 cytokine bias during pregnancy to a Th1 cytokine bias postpartum.60 Clinical trials using daily doses of estriol that are equivalent to the amount produced during pregnancy have shown significant reduction in MS lesions in patients with the relapsing-remitting form of the disease.11

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