First, we discussed differences between men and women who develop multiple sclerosis. Next we explored how hormones, specifically testosterone, play a significant role in men who develop MS. Then, we saw how testosterone and estradiol affect brain damage seen in women with MS. Today, we’re going to explore how the pregnancy hormone estriol could be used to treat women with MS.
Pregnancy and MS
For years, it has been observed that women with auto-immune diseases are affected by pregnancy. Women with MS (as well as RA or other inflammatory diseases) may experience an improvement of symptoms during pregnancy, but can also experience a temporary “rebound” exacerbation postpartum (3-6 months after the baby is born). It is believed that the change in hormones occurring during pregnancy causes this temporary clinical improvement or temporary relapse.
Research is inconclusive as to if clinical improvement and reduced relapse rates during pregnancy improve long-term outcomes. One short-term study (over 2 years) indicated that a single pregnancy has no real ‘net’ effect on disability. However, a long-term study showed that patients who had at least one pregnancy after the onset of MS were wheelchair dependent after 18.6 years, versus 12.5 years for women who did not have children after MS onset.
Contrary to accepted belief that pregnancy improves MS symptoms during pregnancy, several mothers I know have said the opposite was their experience. So perhaps, we really should say that - statistically - pregnancy seems to positively, and temporarily, effect women with auto-immune diseases.
Estriol and Pregnancy
Pregnancy is characterized by the presence of potentially immuno-modulatory and neuroprotective hormones including estrogens, cortisol, progesterone, and prolactin. It is believed that the secretion of these factors are important for the CNS neuronal and oligodendroglial cell lineages during development of the baby. The mother’s body goes through many other changes as well.
Estriol is the estrogen hormone which is most significant for multiple sclerosis. It is produced by the placenta during pregnancy and seems to have a protective quality on the immune system, as well as the central nervous system, for the mother. Used therapeutically, estriol has been shown to have anti-inflammatory as well as neuroprotective effects in women with MS.
Estriol as Therapy
In a pilot study with a crossover design (meaning each participant acted as her own control), estriol was administered to 10 women with MS (six with RRMS and four with SPMS) in an attempt to recreate the protective effect of pregnancy on the disease. After a 6-month pretreatment period to establish baseline, the patients were treated with oral estriol (8 mg/day) for 6 months, observed for another 6 months during the post-treatment period, followed by another 4-month re-treatment period with daily estriol.
As compared with pretreatment baseline, according to the study, relapsing-remitting patients treated with oral estriol demonstrated significant decreases in delayed type hypersensitivity (DTH) responses, a measure of inflammatory immune response. Treatment also decreased the number and volume of gadolinium-enhancing lesions. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels, but when estriol treatment was begun again, enhancing lesions were once again significantly decreased.
In the group as a whole, improvement was driven by the positive effect of estriol treatment in the relapsing-remitting group, not the secondary-progressive group. Also, estriol treatment significantly increased cognitive function as measured by the PASAT (paced auditory serial addition task) in the RRMS group but not in the SPMS group.
Immunological studies involving the same 10 MS patients revealed that oral estriol treatment was associated with “significant decreases in CD4+ and CD8+ T cells and an increase in CD19+ B cells, with no changes in CD64+ monocytes/macrophages.” This means that estriol had a strong immunomodulatory effect. Changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in the relapsing-remitting patients.
In the next post, we will explore how men and women differ in the areas of health-related quality of life, symptom management, and even personality.
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Sicotte NL, Liva SM, Klutch R, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol, 2002 Oct;52(4):421-8.
Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Immune Modulation in Multiple Sclerosis Patients Treated with the Pregnancy Hormone Estriol. J Immunology, 2003;171:6267-6274.
Gold SM and Voskuhl RR. Estrogen and Testosterone Therapies in Multiple Sclerosis. Prog Brain Res, 2009 ; 175: 239–251.