Estrogen treatment in multiple sclerosis

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.

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).