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    So estriol is the culprit, not prolactin.

    I would hope that the women can begin taking the drug now and not have to wait until the next series of trials is complete and the results are in. The drug is already FDA approved.


      Originally posted by antiquity
      So estriol is the culprit, not prolactin.

      I would hope that the women can begin taking the drug now and not have to wait until the next series of trials is complete and the results are in. The drug is already FDA approved.

      I did a literature search on esteriol and multiple sclerosis. The possible beneficial effects of estrogen and estrogen derivatives have long been posulated for multiple sclerosis. In 1994, Janssen, et al. reported that estrogen itself prevents experimental autoimmune encephalomyelitis induced arthritis in mice. In 1998, Correale & Gilmore reported that estradiol (E2) modifies cytokine secretion by CD3+ T cells ioslated from patients with demyelinating diseases, multiple sclerosis, and also normal control subjects. They found that estrone (E1) and esteriol (E3) also enhance secretion of anti-inflammatory IL-10. In 1999, Kim, et al. reported that estriol ameliorates autoimune demyelinating disease in animal models. In 2000, Drew & Chavis showed that female sex steroid homones (estrogen and progesterone) inhbited production of ntiric oxide synthetase (iNOS) and microglial cell activation. Zang, et al. (2002) found that estriol inhibits the pro-inflammatory transcription factor NF-kappa-B.

      On the other hand, it is well known that women are more susceptible to mutliple sclerosis than men, even though they have higher resting levels of estrogen and progesterone. Although females are less susceptible during pregnancies (Voskuhl & Palazynski, 2001; Voskuhl, 2002), one question that has not been asked is whether this simply returns their susceptibility to the same as men.

      In 2002, Sicotte, et al., treated female MS patients with estriol (8 mg/day) and found that this significantly reduced delayed hypersensitivity responses to tetanus, decreased interferon-gamma levels in peripheral blood mononuclear cells, and shrank gadolinium enhancing lesion numbers and volumes on MRI. When estriol treatments were stopped, the lesions increased back to pre-treatment levels. In 2003, Soldan did a second study and found that estriol treatment reduced cytokines and reduction of enhancing lesions in patients with relapsing, remitting multiple sclerosis. In 2004, Palazynski, et al. found that estriol ameliorates disease in male mise with experimental autoimmune encephalomyeltis and suggested that esteriol may be useful for treating males with multiple sclerosis as well.

      Based on these kinds of results, doctors are already using a variety of treatments that are not FDA approved for MS, to treat people with relapsing MS. For example, drugs that are now prescribed by doctors to treat relapses include the statins, mycophenolate mofetil, monoclonal antibodies (alemtuzumab, daclzumab, natalizumab, and rituximab), antibiotics, antivirals, and estriol, and combinations (Rizvi & Bashir, 2004).

      By the way, the article that you cited referred to esteriol which is different from estriol. What is the difference between estriol and esteriol? Here is a picture of estriol.

      I think that esteriol is 17-beta-estradiol:


      1. Jansson L, Olsson T and Holmdahl R (1994). Estrogen induces a potent suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis in mice. J Neuroimmunol 53: 203-7. We have earlier described a chronic relapsing experimental autoimmune encephalomyelitis (EAE) in B10.RIII mice induced with a peptide of myelin basic protein (MBP), mimicking the course of multiple sclerosis in man. We now show that estrogens ameliorate chronic EAE. Castration of female mice led to an earlier disease onset (day 9 +/- 2 postimmunization (p.i.) in castrated mice vs. day 16 +/- 4 p.i. in normal mice). Long-term treatment with high levels of 17 beta-estradiol (E2) given as Silastic implants led to a dramatically delayed onset of disease in both castrated and normal female mice (mean onset day was day 39 +/- 14 and day 50 +/- 3, respectively). Treatment of castrated females by injections of E2, at a concentration which induces the serum levels seen at late stage pregnancy, delayed the onset approximately 1 week (mean onset 21 +/- 8). In contrast, treatment with estriol (E3), which was also given at doses corresponding to those levels seen during pregnancy, delayed the disease onset for a longer time (mean onset day 31 +/- 5). Five times higher doses of E2, compared with those seen during pregnancy, were required to obtain similar effects as the low E3 dose. The same mouse strain (B10.RIII) is also susceptible to induction of collagen-induced arthritis (CIA). We show here that also CIA is suppressed by the same treatments with E2 and E3, suggesting that similar estrogen-mediated mechanisms may operate to suppress these T-cell-dependent autoimmune disease models. Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
      2. Correale J, Arias M and Gilmore W (1998). Steroid hormone regulation of cytokine secretion by proteolipid protein-specific CD4+ T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol 161: 3365-74. Steroid hormones have long been known to modulate immune function, and recent studies indicate that one of the means by which they do so involves effects on the secretion of immunoregulatory cytokines. Our laboratory has found recently that estradiol (E2) selectively modifies cytokine secretion in proteolipid protein (PLP)-specific, CD4+ T cell clones isolated from patients with the demyelinating disease, multiple sclerosis, and from normal control subjects. The data suggest that E2 may play a role in regulating the balance between pro- and antiinflammatory conditions, especially at concentrations typical of pregnancy. To determine whether other pregnancy-associated steroid hormones are capable of similar activity, we expanded our testing to include estrone (E1), estriol (E3), progesterone, and dexamethasone. The results indicate that E1 and E3 enhance secretion of Ag- or anti-CD3-stimulated IL-10 and IFN-gamma in dose-dependent fashion, almost identical to that of E2. The effect on IL-10 was more potent than occurred with IFN-gamma. In addition, E1 and E3, like E2, had a biphasic effect on TNF-alphabeta secretion, with low concentrations stimulatory, and high doses inhibitory. None of the estrogens influenced IL-4 or TGF-beta secretion. Progesterone enhanced secretion of IL-4, without affecting any other tested cytokine. Finally, dexamethasone induced TGF-beta secretion, but inhibited IFN-gamma and TNF-alphabeta. This differential effect of steroid hormones on the secretion of cytokines by CD4+ human T cell clones is consistent with the possibility that, collectively, they promote antiinflammatory conditions at high concentrations typical of pregnancy. Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033, USA.
      3. Kim S, Liva SM, Dalal MA, Verity MA and Voskuhl RR (1999). Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology 52: 1230-8. OBJECTIVE: To evaluate the use of estriol in the treatment of experimental autoimmune encephalomyelitis (EAE) and other cell mediated autoimmune diseases. BACKGROUND: Experimental autoimmune encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune demyelinating disease that is a useful model for the study of immune responses in MS. Interestingly, both EAE and MS have been shown to be ameliorated during late pregnancy. METHODS: Estriol, progesterone, and placebo pellets were implanted in mice during the effector phase of adoptive EAE. Disease scores were compared between treatment groups, and autoantigen-specific humoral and cellular responses were examined. RESULTS: Estriol treatment reduced the severity of EAE significantly compared with placebo treatment whereas progesterone treatment had no effect. Estriol doses that induced serum estriol levels that approximated estriol levels during late pregnancy were capable of ameliorating disease. Estriol-treated EAE mice had significantly higher levels of serum antibodies of the immunoglobulin (Ig) G1 isotype specific for the autoantigen myelin basic protein (MBP). Further, MBP-specific T-lymphocyte responses from estriol-treated EAE mice were characterized by significantly increased production of the Th2 cytokine interleukin 10 (IL-10). T lymphocytes were shown to be the primary source of IL-10 within antigen-stimulated splenocyte populations. CONCLUSIONS: Estriol as a hormone involved in immune changes during pregnancy may provide a basis for the novel therapeutic use of estriol for MS and other putative Th1-mediated autoimmune diseases that improve during late pregnancy. Department of Neurology, University of California Los Angeles School of Medicine, USA.
      4. Drew PD and Chavis JA (2000). Female sex steroids: effects upon microglial cell activation. J Neuroimmunol 111: 77-85. Multiple sclerosis occurs more commonly in females than males. However, the mechanisms resulting in gender differences in multiple sclerosis are unknown. Activated microglia are believed to contribute to multiple sclerosis pathology, perhaps in part due to production of nitric oxide (NO) and TNF-alpha, molecules which can be toxic to cells including oligodendrocytes. The current study demonstrates that the female sex steroids estriol, beta-estradiol and progesterone inhibit lipopolysaccharide (LPS) induction of nitric oxide (NO) production by primary rat microglia and by the mouse N9 microglial cell line. These hormones act by inhibiting the production of inducible nitric oxide synthase (iNOS) which catalyses the synthesis of NO. Estriol likely inhibits iNOS gene expression since the hormone blocks LPS induction of iNOS RNA levels. The pro-inflammatory cytokines IFN-gamma and TNF-alpha are believed to be important modulators of multiple sclerosis. Here, we demonstrate that estrogens and progesterone also inhibit NO production by microglial cells activated in response to these cytokines. Activated microglia elicit TNF-alpha in addition to NO and we further demonstrate that estrogens and progesterone repress TNF-alpha production by these cells. Finally, estriol and progesterone, at concentrations consistent with late pregnancy, inhibit NO and TNF-alpha production by activated microglia, suggesting that hormone inhibition of microglial cell activation may contribute to the decreased severity of multiple sclerosis symptoms commonly associated with pregnancy. University of Arkansas for Medical Sciences, Department of Anatomy, Slot 510, Shorey Bldg., Rm. 922, 4301 W. Markham St., 72205, Little Rock, AR, USA.
      5. Voskuhl RR and Palaszynski K (2001). Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. Neuroscientist 7: 258-70. For decades, it has been known that females are more susceptible than males to multiple sclerosis (MS). It has also long been appreciated that during late pregnancy there is a decrease in MS disease activity. Interestingly, these two observations have also been made in an extensively used animal model for MS, experimental autoimmune encephalomyelitis (EAE) in SJL mice. Female mice are more susceptible to disease than male mice, and there is an improvement in disease during late pregnancy. In this review, the role of sex hormones in each of these two observations is characterized in this EAE model using castration and exogenous hormone treatment strategies. The gender difference in EAE susceptibility is due primarily to a protective effect of testosterone in male mice. The decrease in disease severity during late pregnancy appears to be due at least in part to high levels of estriol, which characterize this time period. Department of Neurology, University of California, Los Angeles 90095, USA.
      6. Voskuhl RR (2002). Gender issues and multiple sclerosis. Curr Neurol Neurosci Rep 2: 277-86. Gender-related issues in multiple sclerosis include the important and widely accepted clinical observations that men are less susceptible to the disease than women and also that disease activity in multiple sclerosis is decreased during late pregnancy. This article reviews mechanisms underlying each of these clinical observations and discusses the role of sex hormones in each. Specifically, the protective role of testosterone in young men and the protective role of the pregnancy hormone estriol in pregnant women are discussed. Rationale for novel therapies in multiple sclerosis based on the protective roles of these sex hormones is presented. UCLA Department of Neurology, Reed Neurological Research Center, Room A-145, 710 Westwood Plaza, Los Angeles, CA 90024, USA.
      7. Zang YC, Halder JB, Hong J, Rivera VM and Zhang JZ (2002). Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B. J Neuroimmunol 124: 106-14. The protective role of pregnancy in autoimmune conditions, such as multiple sclerosis (MS), is potentially associated with immune regulation by sex hormones produced during pregnancy. This study was undertaken to examine the regulatory effects of estriol on the T cell functions, including transmigration and the cytokine production. The results revealed for the first time that estriol significantly inhibited T cell transmigration at a concentration range typical of pregnancy, which correlated with decreased T cell expression of matrix metalloproteinase-9. Estriol was also found to alter the cytokine profile of T cells toward Th2 phenotype by up-regulating the production of IL-10 and inhibiting TNFalpha secretion of T cells. However, the inhibitory effects of estriol on T cells were not antigen-dependent. Further characterization indicated that estriol inhibited nuclear transcription factor kappa B (NF-kappa B), which controls a variety of immune-related genes. This study provides new evidence that estriol is a potent regulator for the T cell functions potentially through its interaction with the NF-kappa B signaling pathway. Multiple Sclerosis Research Unit, Baylor-Methodist Multiple Sclerosis Center and Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
      8. Soldan SS, Alvarez Retuerto AI, Sicotte NL and Voskuhl RR (2003). Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol 171: 6267-74. The protective effect of pregnancy on putative Th1-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis. In addition, estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects of oral estriol therapy were assessed. PBMCs collected longitudinally during the trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine profiles of stimulated PBMCs were determined by intracellular cytokine staining (IL-5, IL-10, IL-12 p40, TNF-alpha, and IFN-gamma) and cytometric bead array (IL-2, IL-4, IL-5, IL-10, TNF-alpha, and IFN-gamma). Significantly increased levels of IL-5 and IL-10 and decreased TNF-alpha were observed in stimulated PBMC isolated during estriol treatment. These changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in relapsing remitting multiple sclerosis. The increase in IL-5 was primarily due to an increase in CD4(+) and CD8(+) T cells, the increase in IL-10 was primarily due to an increase in CD64(+) monocytes/macrophages with some effect in T cells, while the decrease in TNF-alpha was primarily due to a decrease in CD8(+) T cells. Further study of oral estriol therapy is warranted in Th1-mediated autoimmune diseases with known improvement during pregnancy. Department of Neurology, Reed Neurological Research Center, University of California School of Medicine, Los Angeles, CA 90095, USA.
      9. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC and Voskuhl RR (2002). Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 52: 421-8. Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8 mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo-controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy. Department of Neurology, Reed Neurological Research Center, University of California Los Angeles, Los Angeles, CA 90095, USA.
      10. Palaszynski KM, Liu H, Loo KK and Voskuhl RR (2004). Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol 149: 84-9. Estrogen treatment has been found to be protective in experimental autoimmune encephalomyelitis (EAE) and possibly multiple sclerosis (MS). We investigated whether the effect of estrogen treatment is gender-specific. Estrogen receptor (ER) expressions, ERalpha and ERbeta, were found to be equivalent in both genders. EAE disease severity in both females and males was decreased with estriol treatment as compared to placebo. Finally, proinflammatory cytokine production during autoantigen-specific immune responses was decreased with estriol treatment in both females and males. These data support a potential role for estriol treatment for men in addition to women with MS. Department of Neurology, Reed Neurological Research Center, University of California School of Medicine, 750 Westwood Plaza, Los Angeles, CA 90095, USA.
      11. Rizvi SA and Bashir K (2004). Other therapy options and future strategies for treating patients with multiple sclerosis. Neurology 63: S47-54. 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. Department of Clinical Neurosciences, Brown University School of Medicine, 2 Dudley Street, Suite 555, Providence, Rhode Island 02905, USA.


        the pictures of estriol and esteriol are not showing up for some reason... but it doesn't matter. They are very similar to each other.



          low activity and rise of estrogens could be a reason of elevated prolactin too. Dostinex Carbengoline is great drug to use in such case. Vitamin B6 200-300 mg per day can help too.


            Originally posted by maxititer
            low activity and rise of estrogens could be a reason of elevated prolactin too.
            I thought that elevated levels of prolactin LOWERED estrogen levels.

            Dostinex Carbengoline is great drug to use in such case.
            It works, but it sure ain't cheap.