Estrogen treatment in multiple sclerosis
Section snippets
Inflammation and neurodegeneration in MS
Multiple sclerosis (MS) is a heterogeneous inflammatory, demyelinating disease of a presumed Th1-autoimmune origin. However, over the last decade, abundant neuroimaging studies have indicated a significant neurodegenerative process in MS [1], [2], [3], [4], [5], [6], particularly in gray matter [5], [6], [7], [8]. Gray matter atrophy has been shown to correlate better with permanent disability than markers of inflammation [3], [5], [6]. Pathological findings in MS have described cortical
The need for new treatment options in MS
The currently approved treatments for relapsing–remitting (RR) MS (Interferon-β; Glatiramer Acetate and Mitoxantrone) as well as emerging therapies including monoclonal antibodies (such as Natalizumab, Alemtuzumab, and Rituximab) and oral drugs currently in Phase III trials (Cladribine, Fingolimod (FTY 72), Teriflunomide, Oral fumarate, and Laquinimod) all target the inflammatory component of MS pathogenesis. While these may exert some indirect neuroprotective effects via inhibition of
Protective mechanisms of estrogens in animal models
It has been previously shown by numerous laboratories that the clinical severity of both active and adoptive experimental autoimmune encephalomyelitis (EAE) is reduced by estrogen (estriol or 17β-estradiol) treatment in several strains of mice (SJL, C57BL/6, B10.PL, B10.RIII) [22], [23], [24], [25], [26], [27], [28], [29], [30]. Estriol treatment has also been shown to be effective in EAE when administered after disease onset [22].
Protective mechanisms of estrogen treatment (both estriol and
Safety and risks of estriol treatment for multiple sclerosis
Concerns regarding the use of estrogens as therapeutic agents have been raised after results became available from the Women's Health Initiative (WHI), a set of clinical trials in a very large group of postmenopausal women receiving hormone-replacement-therapy (HRT) [60]. Participants were treated with conjugated equine estrogens (Premarin) with or without medroxyprogesterone acetate (Provera) versus placebo. The estrogen+progestin trial arm was stopped due increased the risk for a number of
Phase I trial of oral estriol in MS
Estriol was administered in a pilot clinical trial to women with MS in an attempt to recapitulate the protective effect of pregnancy on disease [83]. A cross-over study was used whereby patients were followed for 6 months pre-treatment to establish baseline disease activity, which included cerebral MRI every month and neurological examination every 3 months. The patients were then treated with oral estriol (8 mg/day) for 6 months, then observed for 6 more months in the post-treatment period
Conclusions
A large body of evidence supports the therapeutic potential of estrogens in inflammatory autoimmune diseases. Mechanisms of action include both immunomodulatory and neuroprotective pathways thus suggesting that estrogens could beneficially affect the inflammatory as well as the neurodegenerative component of the disease. We now also have pilot clinical evidence for the effectiveness of estriol in MS. Ongoing phase II/III trials of estrogens in MS will provide more definitive evidence regarding
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Sex hormone signaling and regulation of immune function
2023, ImmunityMenopausal hormone therapy in women with medical conditions
2021, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :There have been no reports of severe SLE exacerbations with HT initiation [87]. Furthermore, oral estradiol has been explored as a treatment for MS due to its impact on immunomodulatory and neuroprotective pathways [88]. Beyond relief from menopause symptoms, treatment with HT has been shown to improve physical function in women with MS [89].
Diseases of the Nervous System
2021, Diseases of the Nervous System