Site logo

Estrogen Treatment and MS

Estrogen Treatment and MS The first major study to examine the effects of pregnancy on MS was the "Pregnancy in Multiple Sclerosis Study" (PRIMS),2 which examined 254 women between 4 and 36 weeks gestation. Women were examined by a neurologist at 20 and 28 weeks gestation, depending on the time of enrolment, and at 36 weeks. Postpartum, they were examined at 3, 6 and 12 months. The results showed that during the last trimester, relapse rates were substantially lower, and in the first three months postpartum, relapses were higher compared to the pre-pregnancy stage. In the remaining follow up periods, disease status was similar to that prior to pregnancy.

Estrogen Treatment and MS The first major study to examine the effects of pregnancy on MS was the “Pregnancy in Multiple Sclerosis Study” (PRIMS),2 which examined 254 women between 4 and 36 weeks gestation. Women were examined by a neurologist at 20 and 28 weeks gestation, depending on the time of enrolment, and at 36 weeks. Postpartum, they were examined at 3, 6 and 12 months. The results showed that during the last trimester, relapse rates were substantially lower, and in the first three months postpartum, relapses were higher compared to the pre-pregnancy stage. In the remaining follow up periods, disease status was similar to that prior to pregnancy. 

The risk of relapse was not related to the use of epidurals and was also lower in women who breastfed. The overall rate of progression of the disease did not change, but the decrease in the relapse rate during pregnancy was more marked than any other intervention previously reported. Following this observational study, clinical trials were conducted to determine whether supplementing with estriol could induce the same effect in non-pregnant females with MS. In one study, women between the ages of 28 and 50 were included, 6 with SPMS and 4 with RRMS.8 There were 4 phases to the trial; a 6 month pre-treatment phase where women received monthly magnetic resonance imaging (MRI) studies to establish a baseline; a 6 month treatment phase where women were supplemented with 8 mg/day of oral estriol; a 6 month post-treatment observation period; and finally a 4 month re-treatment phase with estriol supplementation once again. Blood tests were taken during the treatment phases and showed that estriol levels in the blood were similar to those of six-month pregnant females.

For safety concerns, gynaecological exams and mammograms were performed at the beginning and end of the study, with no evidence of hyperplasia. Results showed that estriol was well tolerated with only a few women having menstrual cycle irregularities. Additionally, the size and number of neurological lesions shown on MRI decreased in all 10 patients during the treatment and re-treatment phases, but only reached significance in the RRMS patients. Lesions returned to the original size and number Sex Hormone Treatments for Multiple Sclerosis 3 during the six month observation period. Additionally, all participants were given the same cognitive function test.

The cognitive function scores improved in the RRMS group, but not in the SPMS group. This preliminary evidence is promising. Since remissions result from a TH1 dominant state shifting to a TH2 dominant state, it would be interesting to ascertain whether estriol affects changes in cytokine production related to these immunological changes. A study evaluated RRMS patients given 8 mg/ day of estriol in combination with 100 mg/ day of progesterone (i.e., to protect against endometrial hyperplasia).9 Monthly MRIs and blood draws were taken and peripheral blood mononuclear cells were isolated and analyzed to detect cytokine secretion. During the treatment and re-treatment phases, IL-5 and IL-10, and both TH2 associated cytokines were significantly increased, while TNF-α and IFN-γ, and TH1 associated cytokines were significantly decreased. There was no effect on IL-2 and IL-4. Like the previous study, lesions on MRI decreased in size and number in the RRMS group only.

Therefore, it appears that there is a relationship between estriol supplementation and its ability to support a shift from TH1 to TH2 dominance, which is associated with decreased lesions as evidenced by MRI findings. However, this effect seems to only be beneficial in women with RRMS compared to women with SPMS. RRMS is characterized by inflammation, whereas SPMS is characterized by neuronal cell loss and degeneration with little inflammation. Treatments that moderate cytokine production and reduce inflammation are therefore more efficacious among patients with RRMS. Subsequent studies have continued to further examine the effects of estriol supplementation on symptoms of MS. Ten women with MS (6 with RRMS and 4 with SPMS) were supplemented with 8 mg/day of oral estriol for 6 months, followed by a 6 month observation period and 4 month re-treatment period.4 In the RRMS group, MRIs showed fewer lesions during the treatment period, which returned to baseline during the post-treatment period, only to again decrease during the pre-treatment period. Improvements in cognitive function were also observed. No significant clinical benefits were shown in the SPMS group. Epidemiological evidence has reviewed the use of oral contraceptives (OCs) and the risk of developing MS.10 Data was obtained from 106 women younger than 50 years old with a definitive diagnosis of MS. Women were included if they were either past users or current users of OCs. The types of OCs used in the analysis included synthetic estrogens and progestins. The results showed that users of OCs had a 40% decreased incidence of MS than women who had never used them. While previous research has been extremely mixed on this subject, a recent review suggested that the use of OCs might delay the onset of disease, as opposed to preventing its development.11

Click here for more about this topic, conclusion and references