Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen

Christianson, Mindy S.; Mensah, Virginia; Shen, Wen

doi:10.1016/j.maturitas.2014.11.013

Cited by 26 publications

(20 citation statements)

References 94 publications

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“…One promising approach is enhancing the immunoregulatory properties of the lymphocyte population of invariant natural killer T (iNKT) cells [27]. For many years, estrogen-based therapies have been considered promising immunoregulatory strategies in autoimmune diseases such as multiple sclerosis [28–30]. E2 therapy protects female non-obese diabetic (NOD) mice from autoimmune T1D by preventing islet insulitis [31].…”

Section: Role Of Estrogensmentioning

confidence: 99%

Role of Sex Steroids in β Cell Function, Growth, and Survival

Mauvais-Jarvis

2016

Trends in Endocrinology & Metabolism

104

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The gonads have long been considered as endocrine glands producing sex steroids such as estrogens, androgens and progesterone, for the sole purpose of sexual differentiation, puberty and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in different physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogen, androgen and progesterone via their receptors in pancreatic β-cells in the gender-specific tuning of insulin secretion. We also discuss potential gender-specific therapeutic avenues that this knowledge may open in the future.

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Section: Role Of Estrogensmentioning

confidence: 99%

Role of Sex Steroids in β Cell Function, Growth, and Survival

Mauvais-Jarvis

2016

Trends in Endocrinology & Metabolism

104

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“…Proper hormone therapy (HT) could ameliorate the onset and severity of deterioration, but it has been mired in controversy since the Women’s Health Initiative (WHI). Subsequently, the use of human estradiol (E), as well as administration during the perimenopause, have yielded positive effects on mood [1,2], cognition [3], carotid intima-media thickness (CIMT; [4]), metabolism and body composition [5], lung function [6] and immune function [7] (including multiple sclerosis [8]), compared to no treatment or delayed treatment. In contrast, the ELITE trial reported no difference in cognitive function in women taking oral E within 4 years of menopause or after 10 years of menopause [9].…”

Section: Introductionmentioning

confidence: 99%

Effects of obesogenic diet and estradiol on dorsal raphe gene expression in old female macaques

et al. 2017

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The beneficial effects of bioidentical ovarian steroid hormone therapy (HT) during the perimenopause are gaining recognition. However, the positive effects of estrogen (E) plus or minus progesterone (P) administration to ovariectomized (Ovx) lab animals were recognized in multiple systems for years before clinical trials could adequately duplicate the results. Moreover, very large numbers of women are often needed to find statistically significant results in clinical trials of HT; and there are still opposing results being published, especially in neural and cardiovascular systems. One of the obvious differences between human and animal studies is diet. Laboratory animals are fed a diet that is low in fat and refined sugar, but high in micronutrients. In the US, a large portion of the population eats what is known as a “western style diet” or WSD that provides calories from 36% fat, 44% carbohydrates (includes 18.5% sugars) and 18% protein. Unfortunately, obesity and diabetes have reached epidemic proportions and the percentage of obese women in clinical trials may be overlooked. We questioned whether WSD and obesity could decrease the positive neural effects of estradiol (E) in the serotonin system of old macaques that were surgically menopausal. Old ovo-hysterectomized female monkeys were fed WSD for 2.5 years, and treated with placebo, Immediate E (ImE) or Delayed E (DE). Compared to old Ovx macaques on primate chow and treated with placebo or E, the WSD-fed monkeys exhibited greater individual variance and blunted responses to E-treatment in the expression of genes related to serotonin neurotransmission, CRH components in the midbrain, synapse assembly, DNA repair, protein folding, ubiquitylation, transport and neurodegeneration. For many of the genes examined, transcript abundance was lower in WSD-fed than chow-fed monkeys. In summary, an obesogenic diet for 2.5 years in old surgically menopausal macaques blunted or increased variability in E-induced gene expression in the dorsal raphe. These results suggest that with regard to function and viability in the dorsal raphe, HT may not be as beneficial for obese women as normal weight women.

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“…During pregnancy, levels of estrogen, progesterone, glucocorticoids, h-human chorionic gonadotropin (h-HCG), and thyroid hormones were increased to some degrees. [111213] High level of serum HCG may drive an expansion of interleukin-10 (IL-10)-producing regulatory B-cells, a subtype of B lymphocytes with strong immunosuppressive functions, during pregnancy. [14] Th2 cells mainly secrete IL-6, IL-4 which can stimulate the activation of B lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

“…[16] Progesterone can also protect neuron by thickening myelin sheath and enhancing the fibril connection. [111718]…”

Section: Discussionmentioning

confidence: 99%

Insights into Initial Demyelinating Episodes of Central Nervous System during Puerperium

Chen

Liu

et al. 2017

Chinese Medical Journal

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Background:Inflammatory demyelinating disease of central nervous system (CNS) is an inflammatory disease characterized by a high childbearing female predominance. Labor-related alterations for postpartum demyelinating attacks are not entirely clear. This study aimed to summarize clinical features of female patients of reproductive age with initial CNS inflammatory demyelinating attacks during puerperium.Methods:Fourteen female patients with initial demyelinating events during puerperium between January 2013 and December 2016 were retrospectively studied. Records of clinical features, neuroimaging, serum antibodies, cerebrospinal fluid (CSF) findings, annualized relapse rate (ARR), and treatment were analyzed.Results:Among 14 patients, 5 patients were diagnosed with multiple sclerosis (MS), four as neuromyelitis optica (NMO), two as longitudinal extensive transverse myelitis, two as clinical isolated syndrome (CIS), and one as acute brainstem syndrome. All the 14 puerperal female patients presented with more than one manifestation of hemiplegia, paraplegia, uroschesis, visual loss or dysarthria, and with mild to moderate abnormalities of CSF. Attacks occurred during the first trimester postpartum and cesarean section was the main delivery way (n = 10). Median Expanded Disability Status Scale (EDSS) scores were 5.0 (range: 2.0–9.0) at the onset and 2.5 (range: 0–7.0) at the end of follow-ups. Patients with MS and CIS had a significantly lower EDSS scores than patients with NMO spectrum disorders (P < 0.05). Median ARR was 0.46 (range: 0–1.16); all patients had a low ARR (0.49 ± 0.34, 95% confidence interval: 0.29–0.69) with standardized treatments.Conclusion:Labor-related alterations in the mother's immune system might result in newly-onset demyelinating diseases of central nervous system.

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Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen

Cited by 26 publications

References 94 publications

Role of Sex Steroids in β Cell Function, Growth, and Survival

Role of Sex Steroids in β Cell Function, Growth, and Survival

Effects of obesogenic diet and estradiol on dorsal raphe gene expression in old female macaques

Insights into Initial Demyelinating Episodes of Central Nervous System during Puerperium

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