Hormone Estriol Research Articles

Anelosimuseximius bioinspired ZnO nano cobwebs for environmental remediation of drugs and endocrine disruptors from water

The pollution of wastewater with pharmaceuticals and endocrine-disrupting chemicals (EDCs) in populated areas poses a growing threat to humans and ecosystems. To address this serious problem, various one-dimensional (1D) hierarchical ZnO-based nanostructures inspired by Anelosimus eximius cobwebs were developed and successfully grown on a glass substrate through simple hydrothermal synthesis. The nanorods (nr) obtained during primary growth were chemically etched with KOH (ZnOnr-KOH), followed by the secondary growth of nano cobweb-like (ncw) structures using polyethyleneimine (ZnOnr/ncw). These structures were further decorated by the photoreduction of Ag nanoparticles (ZnOnr/ncw/Ag). The feasibility of ZnO-based 1D nanostructures to remove pollutants was demonstrated by degrading commonly prescribed pharmaceutical drugs (diclofenac and carbamazepine) in a miniature cuvette reactor. The photocatalytic activities for drug degradation generally decreased in the order ZnOnr/ncw/Ag > ZnOnr/ncw > ZnOnr-KOH. Additionally, the suitability of the samples for scaling up and practical application was demonstrated by photocatalytic degradation of the hormone estriol (E3) in a flow-through photoreactor. The photocatalytic degradation efficiency of E3 followed the same trend observed for drug degradation, with the complete elimination of the endocrine disruptor achieved by the best-performing ZnOnr/ncw/Ag within 4 h, due to optimized charge transfer and separation at the heterostructure interface.

Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells – innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes and their cytokines in different ways. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS patients.

Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol

In multiple sclerosis (MS), demyelination occurs in the cerebral cortex, and cerebral cortex atrophy correlates with clinical disabilities. Treatments are needed in MS to induce remyelination. Pregnancy is protective in MS. Estriol is made by the fetoplacental unit, and maternal serum estriol levels temporally align with fetal myelination. Here, we determined the effect of estriol treatment on the cerebral cortex in the preclinical model of MS, experimental autoimmune encephalomyelitis (EAE). Estriol treatment initiated after disease onset decreased cerebral cortex atrophy. Neuropathology of the cerebral cortex showed increased cholesterol synthesis proteins in oligodendrocytes, more newly formed remyelinating oligodendrocytes, and increased myelin in estriol-treated EAE mice. Estriol treatment also decreased the loss of cortical layer V pyramidal neurons and their apical dendrites and preserved synapses. Together, estriol treatment after EAE onset reduced atrophy and was neuroprotective in the cerebral cortex.

Гормональная и бактериальная регуляция фенотипических изменений врожденных лимфоидных клеток (ILC) у больных рассеянным склерозом и здоровых доноров

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of innate immunity cells – innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC cells in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes in different ways. In particular, MS patients’ cells are more susceptible to hormonal modulation, while those of healthy donors are more susceptible to bacterial modulation. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS.

Photocatalytic Degradation and Mineralization of Estriol (E3) Hormone Using Boron-Doped TiO2 Catalyst

In this research work, boron-doped titanium oxide (B-TiO2) was prepared by the sol-gel method to investigate its behavior in the degradation of the recalcitrant hormone estriol (E3). The doped photocatalyst was synthesized at different boron/titania ratios of 2, 3, and 5 wt.% of boron with respect to the TiO2 content. The obtained materials were characterized by UV-Vis diffuse reflectance spectroscopy (DRS), X-ray diffraction (XRD), Raman spectroscopy, Scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The textural properties, specific surface area, and porosity were obtained from N2 adsorption–desorption isotherms by BET and BJH methods, respectively. The photocatalytic performance of each synthesized catalyst was evaluated on the degradation of an aqueous solution (10 mg/L) of estriol (E3) under simulated solar radiation. The variation in the hormone concentration was determined by the HPLC technique, and the mineralization was evaluated by the quantification of total organic carbon (TOC). The obtained results indicated that the catalyst with 3 wt.% of boron incorporation exhibited the best performance on the degradation and mineralization of estriol, achieving its complete degradation at 300 kJ/m2 of accumulated energy and 71% of mineralization at 400 kJ/m2 (2 h) obtaining a non-toxic effluent.

The steroid hormone estriol (E3) regulates epigenetic programming of fetal mouse brain and reproductive tract

BackgroundEstriol (E3) is a steroid hormone formed only during pregnancy in primates including humans. Although E3 is synthesized at large amounts through a complex pathway involving the fetus and placenta, it is not required for the maintenance of pregnancy and has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, estrogen exposure during pregnancy may have an effect on organs both within and outside the reproductive system, and compounds with binding affinity for estrogen receptors weaker than E3 have been found to impact reproductive organs and the brain. Here, we explore potential effects of E3 on fetal development using mouse as a model system.ResultsWe administered E3 to pregnant mice, exposing the fetus to E3. Adult females exposed to E3 in utero (E3-mice) had increased fertility and superior pregnancy outcomes. Female and male E3-mice showed decreased anxiety and increased exploratory behavior. The expression levels and DNA methylation patterns of multiple genes in the uteri and brains of E3-mice were distinct from controls. E3 promoted complexing of estrogen receptors with several DNA/histone modifiers and their binding to target genes. E3 functions by driving epigenetic change, mediated through epigenetic modifier interactions with estrogen receptors rather than through canonical nuclear transcriptional activation.ConclusionsWe identify an unexpected functional role for E3 in fetal reproductive system and brain. We further identify a novel mechanism of estrogen action, through recruitment of epigenetic modifiers to estrogen receptors and their target genes, which is not correlated with the traditional view of estrogen potency.

Estriol in regulation of cell-mediated immune reactions in multiple sclerosis

The effect of pregnancy hormone estriol (E3) on innate and adaptive immunity cells functions in patients with multiple sclerosis (MS) in comparison with healthy donors (HD) was studied. E3 inhibited phagocytic activity of neutrophils and enhanced monocytes IDO activity. Treg percentage increased and number of Th17 and iNKT cells decreased under E3 influence. At the same time, E3 stimulated production of IL-10 and inhibited secretion of IL-17. The hormonal effects were realized on the cells of both HD and MS patients. Thus, the MS amelioration during pregnancy may be related to E3 influence.

Does Active Smoking Influence the Second Trimester Biochemical Markers Concentrations?

Cigarette smoke contains over 7000 different substances some of them exerting harmful effects on embryo and pregnant woman. Nowadays 15 % of adult people and around 10-15% of pregnant women smoke. Previous studies showed that cigarette smoke compounds could exert pharmacodinamic effects and influence some of the second trimester biochemical markers concentration. Therefore there is a need to adjust the reference values of second trimester markers depending of the smoker status. The aim of our study was to analyse which of the markers are influenced by smoking and whether the software used to calculate the risk for aneuploidies is able to counterbalance this influence. Alpha-fetoprotein (AFP), chorionic gonadotropin hormone (hCG) and free estriol (uE3) values were measured in second trimester sera of 1242 pregnant women: 1089 non-smokers and 153 smokers. Only hCG second trimester values were influenced by smoking whereas AFP and uE3 values were not. The correction of medians according to the smoking status was able to counterbalance this effect.

ОПТИМІЗАЦІЯ МЕТОДІВ ДІАГНОСТИКИ ПРИ ЗАТРИМЦІ РОСТУ ПЛОДА У ВАГІТНИХ.

У статті представлені результати пошуку маркерів ранньої діагностики затримки росту плода та оцінка їх ефективності. Проведено дослідження 45 вагітних з затримкою росту плода, що перебували на лікуванні у Тернопільській комунальній міській лікарні № 2. Контрольну групу склали 25 вагітних з фізіологічним перебігом вагітності, які народили живих доношених дітей з масо-ростовими характеристиками відповідно до гестаційного віку. Вивчали стан фетоплацентарного комплексу у вагітних на основі дослідження рівнів гормонів (ПАПП-А, β-хоріонічного гонадотропіну людини (β-ХГЛ), естріолу (Е3), плацентарного лактогену (ПЛ) та прогестерону). Стан внутрішньоутробного плода оцінювали за даними ультразвукового дослідження, кардіотокографії, визначення біофізичного профілю плода. Виявлено, що ранніми ознаками розвитку затримки росту плода є визначення ПАПП, естріолу та хоріонічного гонадотропіну в ранні терміни вагітності та рівні естріолу, прогестерону, плацентарного лактогену в другому триместрі. Використання гравідограми як скринінгового маркера дозволив діагностувати затримку росту й у 95,4 % випадків був підтверджений УЗД та виставлено діагноз затримки росту плода у вагітних. За даними УЗД визначали біометричні маркери затримки росту.

Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial

Relapses of multiple sclerosis decrease during pregnancy, when the hormone estriol is increased. Estriol treatment is anti-inflammatory and neuroprotective in preclinical studies. In a small single-arm study of people with multiple sclerosis estriol reduced gadolinium-enhancing lesions and was favourably immunomodulatory. We assessed whether estriol treatment reduces multiple sclerosis relapses in women. We did a randomised, double-blind, placebo-controlled phase 2 trial at 16 academic neurology centres in the USA, between June 28, 2007, and Jan 9, 2014. Women aged 18-50 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1) with a random permuted block design to either daily oral estriol (8 mg) or placebo, each in combination with injectable glatiramer acetate 20 mg daily. Patients and all study personnel, except for pharmacists and statisticians, were masked to treatment assignment. The primary endpoint was annualised relapse rate after 24 months, with a significance level of p=0.10. Relapses were confirmed by an increase in Expanded Disability Status Scale score assessed by an independent physician. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00451204. We enrolled 164 patients: 83 were allocated to the estriol group and 81 were allocated to the placebo group. The annualised confirmed relapse rate was 0.25 relapses per year (95% CI 0.17-0.37) in the estriol group versus 0.37 relapses per year (0.25-0.53) in the placebo group (adjusted rate ratio 0.63, 95% CI 0.37-1.05; p=0.077). The proportion of patients with serious adverse events did not differ substantially between the estriol group and the placebo group (eight [10%] of 82 patients vs ten [13%] of 76 patients). Irregular menses were more common in the estriol group than in the placebo group (19 [23%] vs three [4%], p=0.0005), but vaginal infections were less common (one [1%] vs eight [11%], p=0.0117). There were no differences in breast fibrocystic disease, uterine fibroids, or endometrial lining thickness as assessed by clinical examination, mammogram, uterine ultrasound, or endometrial lining biopsy. Estriol plus glatiramer acetate met our criteria for reducing relapse rates, and treatment was well tolerated over 24 months. These results warrant further investigation in a phase 3 trial. National Institutes of Health, National Multiple Sclerosis Society, Conrad N Hilton Foundation, Jack H Skirball Foundation, Sherak Family Foundation, and the California Community Foundation.

Unique dose-dependent effects of the human pregnancy hormone estriol on the ratio of blood IgM to IgG in female mice.

The present study aimed to investigate the dose-dependent modulating effect of estriol (E3), an estrogen predominantly produced during human pregnancy, on antigen‑induced production of specific antibodies in female BALB/c mice. The animals were immunized either with bovine serum albumin (BSA) or the pneumococcal polysaccharide serotype-14 (PPS-14), and the levels of specific serum antibodies were determined using ELISA kits. E3 was found to have very different effects on antigen-induced production of specific antibodies in animals immunized with these two antigens. While E3 stimulated the production of PPS-14-specific antibodies, it suppressed the production of BSA-specific antibodies. The results also demonstrated that the modulating effect of E3 on the production of antigen‑specific antibodies depends on the dose of E3 used. For BSA‑induced antibody production, E3 had a dose‑dependent inhibitory effect, whereas for PPS‑14‑specific antibody (Ab) production, E3 exerted the strongest stimulation at a lower dose, and produced less stimulation at higher doses. E3 caused thymus atrophy in animals immunized with either PPS‑14 or BSA, but only induced spleen atrophy in BSA‑injected mice. These observations suggest that E3 increases the ability of a pregnant female to avoid bacterial infections while decreasing the incidence of autoimmune responses against circulating components from either the fetus or pregnant female.

Detection of hormones in surface and drinking water in Brazil by LC-ESI-MS/MS and ecotoxicological assessment with Daphnia magna.

The growing use of pharmaceutical drug is mainly due to several diseases in human and in animal husbandry. As these drugs are discharged into waterways via wastewater, they cause a major impact on the environment. Many of these drugs are hormones; in which even at low concentrations can alter metabolic and physiological functions in many organisms. Hormones were found in surface water, groundwater, soil, and sediment at concentrations from nanograms to milligrams per liter of volume--quantities known to cause changes in the endocrine system of aquatic organisms. This study aimed to develop a methodology for hormone detection (estriol, estrone, 17β-estradiol, 17α-ethinylestradiol, progesterone, and testosterone) on surface and treated water samples. Sample toxicity was assessed by ecotoxicology tests using Daphnia magna. A liquid chromatograph coupled to a mass spectrometer with an electrospray ionization source (LC-ESI-MS/MS) was used for the analysis. The results showed that samples were contaminated by the hormones estriol, estrone, progesterone, 17β-estradiol, and 17α-ethinylestradiol during the sampling period, and the highest concentrations measured were 90, 28, 26, 137, and 194 ng · L(-1), respectively. This indicates the inflow of sewage containing these hormones at some points in the Piracicaba River in the State of Sao Paulo-Brazil. Results indicated little toxicity of the hormone estriol in D. magna, indicating that chronic studies with this microcrustacean are necessary.

Effect of Turmeric Powder to Estriol and Progesterone Hormone Profile of Laying Hens During One Cycle of Ovulation

This research was designed to study the profile of the hormones estriol, progesterone, in the blood during a cycle of ovulation in controlled laying hens and laying hens that treated by giving the turmeric powder. Determination of hormone profile was done on laying hens. Six laying hens aged 20 month were divided into two experimental unit. Each experimental unit consist of three laying hens i.e., P0: control (not supplemented with turmeric powder), P1: turmeric powder supplementation at a dose of 405 mg/laying hens/day for a month. Blood was drawn via jugular vein by 4 mL. Blood sampling performed every 2 h starting after hen lay eggs during a cycle of ovulation, then retrieved and analyzed the serum levels of estrogen and progesterone. The data graphed to determine the profile of the hormones estrogen, progesterone and compared between the controlled and the treated with turmeric powder. The results showed that administration of turmeric powder can shorten the cycle of ovulation about 5 h 35 min. Turmeric powder did not affect the pattern of fluctuations in the hormone progesterone. There are 4 progesterone peaks during the first cycle of ovulation both in controlled laying hens and laying hens that treated with turmeric powder. There was a change to the hormone estriol fluctuations. In controlled laying hens takes four peaks hormone estriol in an ovulatory cycle, whereas in laying hen treated with turmeric powder was 1 hormone estriol peak occurring approximately 15 h before ovulation.

Sonophotolytic Degradation of Estriol at Various Ultraviolet Wavelength in Aqueous Solution

This study investigated degradation of the hormone estriol by sonolysis, photolysis and sonophotolysis at various UV wavelengths. Degradation was determined with UVA (365 nm), UVC (254 nm), or VUV (185 nm) irradiation and/or ultrasound exposure (283 kHz). The pseudo-first order degradation rate constants were in the order of 10-1 to 10-4 min-1 depending on the processes. The dominant reaction mechanism of estriol in sonolysis was estimated as hydroxyl radical reaction by the addition of tert-butanol (t-BuOH), which is a common hydroxyl radical scavenger. Photolytic and sonophotolytic estriol degradation rate also were high at shortest UV wavelength (VUV) due to the higher energy of photons, higher molar absorption coefficient of estriol and increased hydroxyl radical generation from the homolysis of water. Small synergistic effects were observed for sonophotolytic degradation with UVA and UVC irradiation. No synergy was observed for sonophotolysis with VUV irradiation.

Tolerogenic DC differentiation and development of immunosuppressive DC precursors (48.13)

Abstract Tolerogenic dendritic cells (tDCs) are important myeloid cells which potently regulate innate and adaptive immune responses. We have previously found that the steroid hormone estriol (E3) generates tDCs in vivo which protect mice from developing autoimmune disease. To better understand tDC generation, we developed an in vitro tDC differentiation model. Myeloid progenitors were differentiated with GM-CSF in the presence of steroid hormones E3 and retinoic acid (RA) and both differentiated tDCs and their precursors (pre-tDCs) were phenotypically and functionally evaluated. We found that both E3 and RA tDCs had increased expression of stimulatory and inhibitory costimulatory markers and suppressed proliferation of responder immune cells in a dose-dependent manner, similar to in vivo tDCs. Interestingly, we also found that pre-tDC had enhanced immunosuppressive abilities over differentiated tDCs without marked changes in phenotypic cell composition. Although CD11b+Gr1+ populations were unchanged, increases in FoxP3+ expression were seen in responder splenocyte populations when co-cultured with pre-tDCs. These results suggest that pre-tDCs may be acting as myeloid derived suppressor cells (MDSCs) and are a potently immunosuppressive immature myeloid population that gives rise to tDCs. A better understanding of how tDCs are generated has potential therapeutic relevance for the treatment of numerous inflammatory diseases.

Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERα)

Matrix metalloproteinases (MMPs) have a crucial function in migration of inflammatory cells into the central nervous system (CNS). Levels of MMP-9 are elevated in multiple sclerosis (MS) and predict the occurrence of new active lesions on magnetic resonance imaging (MRI). This translational study aims to determine whether in vivo treatment with the pregnancy hormone estriol affects MMP-9 levels from immune cells in patients with MS and mice with experimental autoimmune encephalomyelitis (EAE). Peripheral blood mononuclear cells (PBMCs) collected from three female MS patients treated with estriol and splenocytes from EAE mice treated with estriol, estrogen receptor (ER) α ligand, ERβ ligand or vehicle were stimulated ex vivo and analyzed for levels of MMP-9. Markers of CNS infiltration were assessed using MRI in patients and immunohistochemistry in mice. Supernatants from PBMCs obtained during estriol treatment in female MS patients showed significantly decreased MMP-9 compared with pretreatment. Decreases in MMP-9 coincided with a decrease in enhancing lesion volume on MRI. Estriol treatment of mice with EAE reduced MMP-9 in supernatants from autoantigen-stimulated splenocytes, coinciding with decreased CNS infiltration by T cells and monocytes. Experiments with selective ER ligands showed that this effect was mediated through ERα. In conclusion, estriol acting through ERα to reduce MMP-9 from immune cells is one mechanism potentially underlying the estriol-mediated reduction in enhancing lesions in MS and inflammatory lesions in EAE.

Estrogen and testosterone therapies in multiple sclerosis

It has been known for decades that females are more susceptible than men to inflammatory autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis, and psoriasis. In addition, female patients with these diseases experience clinical improvements during pregnancy with a temporary "rebound" exacerbation postpartum. These clinical observations indicate an effect of sex hormones on disease and suggest the potential use of the male hormone testosterone and the pregnancy hormone estriol, respectively, for the treatment of MS. A growing number of studies using the MS animal model experimental autoimmune encephalomyelitis (EAE) support a therapeutic effect of these hormones. Both testosterone and estriol have been found to induce anti-inflammatory as well as neuroprotective effects. Findings from two recent pilot studies of transdermal testosterone in male MS patients and oral estriol in female MS patients are encouraging. In this paper, we review the preclinical and clinical evidence for sex hormone treatments in MS and discuss potential mechanisms of action.

Unique effect of the pregnancy hormone estriol on antigen-induced production of specific antibodies in female BALB/c mice

We investigated the modulatory effect of estriol (E 3), an estrogen predominantly produced during human pregnancy, on the antigen-induced production of specific antibodies in female BALB/c mice, and its effect was compared with 17β-estradiol (E 2). Estriol (E 3) had a very different effect than E 2 on the antigen-induced production of specific antibodies in animals immunized with two different antigens, i.e., the bovine serum albumin (BSA) and pneumococcal polysaccharide serotype-14 (PPS-14). While E 2 strongly stimulated the production of BSA-specific antibodies (mostly IgG1), E 3 had little or no effect on their production. In comparison, when the bacterial PPS-14 was the immunogen, E 3 and E 2 both strongly increased the production of PPS-14-specific antibodies (mostly IgM). E 3 and E 2 also had a similar effect on the thymus weight reduction and on the spontaneous antibody production in these animals. Our results provided an example demonstrating that the pregnancy hormone E 3 has a distinctly different profile of modulatory actions in the immune system compared to E 2, while the former strongly enhanced the body's ability to produce bacteria-specific IgM antibodies, it had no effect on the production of specific antibodies against a soluble protein. This differential effect of E 3 may be beneficial for reducing the risk of developing antibody-mediated immune attack against the maternal and fetal elements during pregnancy.

Osteogenic Potential of Estriol-Treated Cultured Bone - In Vitro and In Vivo -

Osseous tissue can be formed by culturing marrow cells with compounds such as dexamethasone and that a bone matrix cultured in this manner possesses BMP activity. We have reported that artificial bones with a high level of osteogenic potential can be prepared by culturing artificial bone materials with cultured osseous tissue. Here, in an attempt to develop activated cultured bone constructs with even greater osteogenic potential, the effects of the female hormone estriol on osteogenesis were investigated. Bone marrow cells were collected from the femur shafts of 7-week-old male Fischer rats, and subjected to primary and secondary cultures. During secondary culture with or without dexamethasone (Dx), 10-5, 10-6, 10-7, 10-8 or 10-9 M of estriol was added to a standard culture medium containing ascorbic acid and β-glycerophosphosphate. The alkaline phosphatase(ALP) activity and Ca levels were measured and statistically analyzed. There was a significant difference in ALP activity between the control group and the estriol groups, and ALP activity was the highest in the 10-7 and 10-8 M groups, being about 2.5 times higher than in the control group. Similar results were seen for Ca levels. Furthermore, in vivo study showed10-7M-estriol-treated-cultured bone/ceramic construct has significant high osteogenic potential when it is grafted into in vivo. Estriol has been reported to increase bone mass, and the results of the present study suggest that the osteogenic potential of cultured bone constructs can be more than doubled by adjusting the concentration of estriol in bone marrow cell culture. Therefore, the use of estriol may be able to facilitate osteogenesis in bone regeneration therapy.

Other therapy options and future strategies for treating patients with multiple sclerosis

Research into therapy for multiple sclerosis (MS) is occurring at a rapid pace, and current treatment options approved by the FDA specifically target the inflammatory phase of MS. However, drugs that are not FDA-approved are routinely used to treat MS. One example is corticosteroids, which are commonly used to treat acute relapses. Other drugs that are commonly used to treat patients who do not respond to the FDA-approved agents include the following: methotrexate, azathioprine, cyclophosphamide, and pulse steroids. Drugs being studied as possible therapeutic agents include the statins, mycophenolate mofetil, various monoclonal antibodies (e.g., alemtuzumab, daclzumab, natalizumab, and rituximab), antibiotics and antivirals, and the pregnancy hormone estriol. Disease modifying agents (DMAs) that promote remyelination would be beneficial for preventing long-term disability, and such agents are also under active investigation (e.g., IV immunoglobulin G and stem cell transplantation). Combination therapy with DMAs with different mechanisms of action may be advantageous in the future for providing optimal treatment that both delays the progression of disability and promotes repair and remyelination.