Estrogen treatment in multiple sclerosis - PubMed (original) (raw)
Estrogen treatment in multiple sclerosis
Stefan M Gold et al. J Neurol Sci. 2009.
Abstract
Currently available treatments for multiple sclerosis (MS) reduce inflammatory lesions on MRI and decrease clinical relapses but have limited effects on disability. Novel treatment options that target both the inflammatory as well as the neurodegenerative component of the disease are therefore needed. A growing body of evidence from basic science and clinical studies supports the therapeutic potential of estrogens in MS. Mechanisms of action include both immunomodulatory and directly neuroprotective pathways. A first pilot trial of oral estriol treatment showed encouraging results. There are now several phase II trials underway to further determine the efficacy of estrogen treatment in MS.
Figures
Figure 1
Direct and indirect neuroprotection in multiple sclerosis. Drugs currently approved for treatment of relapsing-remitting MS (Interferon-β, Glatiramer Acetate, Mitoxantrone) are targeted at the immune system and mainly confer anti-inflammatory effects. While this may exert some indirect neuroprotection by reducing the immune attack on neurons and oligodendrocytes, no approved treatment directly protects CNS cells and/or promotes regeneration and repair (direct neuroprotection). Studies using in vitro systems and in vivo models indicate that estrogen treatment has the potential to be both anti-inflammatory and directly neuroprotective (see text for details).
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References
- Brex PA, Jenkins R, Fox NC, Crum WR, O'Riordan JI, Plant GT, et al. Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology. 2000 Apr 25;54(8):1689–1691. - PubMed
- Filippi M, Bozzali M, Rovaris M, Gonen O, Kesavadas C, Ghezzi A, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003 Feb;126(Pt 2):433–437. - PubMed
- Ge Y, Grossman RI, Udupa JK, Wei L, Mannon LJ, Polansky M, et al. Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis. Radiology. 2000;214(3):665–670. - PubMed
- Losseff NA, Wang L, Lai HM, Yoo DS, Gawne CM, McDonald WI, et al. Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain. 1996:2009–2019. - PubMed
- Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology. 1999;53(8):1698–1704. - PubMed
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