Literature review & commentary

Townsend Letter for Doctors and Patients, Nov, 2003 by Alan R. Gaby

Treatment of multiple sclerosis with estriol

Twelve non-pregnant women (mean age, 44 years) with multiple sclerosis (MS) were treated with 8 mg/day of estriol for 6 months. Compared with baseline, 3 months of estriol treatment resulted in a significant 82% decrease in the median number of inflammatory lesions (gadolinium enhancing lesions) of the brain, as determined by MRI, and a significant 79% decrease in total lesion volumes. These improvements were maintained at 6 months. When estriol was discontinued, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Improvement was seen only in the six patients with relapsing remitting MS, not in the four with secondary progressive MS. Three women developed abnormal menstrual bleeding during estriol treatment; all three had biopsies, which were negative for endometrial hyperplasia.

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Comment: Women with MS experience a significant decrease in relapses during pregnancy. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can reduce disease severity. The results of the present study suggest that estriol may be beneficial in the treatment of women with relapsing remitting MS. Long-term placebo-controlled trials are needed to confirm the benefits of estriol, since the improvement could have been due to a placebo effect, or to spontaneous seasonal fluctuations (possibly related to vitamin D levels) which are known to occur in people with MS.

In contrast to the more commonly used forms of estrogen, estriol rarely causes uterine hyperplasia, and does not appear to be carcinogenic. Estriol has been used in Europe and Japan for more than 20 years to treat postmenopausal women, and it appears to be relatively safe.

Sicotte NL, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002;52:421-428.

Huntington's disease:

improvement with fatty acid treatment

Seven patients with end-stage (stage III) Huntington's disease were randomly assigned to receive, in double-blind fashion, 1 g twice a day of the ethyl-ester of eicosapentaenoic acid (E-EPA) or placebo for 6 months. After 6 months, all patients treated with E-EPA improved on the orofacial component of the Unified Huntington's Disease Rating Scale, whereas all patients receiving placebo deteriorated (p<0.03). On the total movement scale, two patients (both in the E-EPA group) improved, while the other five deteriorated; the change in the total movement score differed significantly between groups (p<0.02), in favor of the active-treatment group. Two patients in each group underwent MRI brain scans before and after treatment; both patients in the placebo group showed progressive cerebral atrophy, whereas both patients in the E-EPA group showed a reversal of cerebral atrophy.

Comment: Huntington's disease is a progressive and ultimately fatal neurodegenerative disease that is inherited in an autosomal-dominant fashion. There is no known effective treatment. EPA plays an important role in the structure and function of the brain. Recent studies have shown that E-EPA is clinically beneficial in the treatment of some cases of depression and schizophrenia. Moreover, treatment with E-EPA appeared to reverse cerebral atrophy in a patient with schizophrenia and induced structural changes in the brain including a reduction in the lateral ventricular volume (in conjunction with marked clinical improvement) in a patient with chronic depression. Taken together, these studies suggest that E-EPA treatment can lead to profound, positive changes in the structure and function of the brain. Controlled trials of E-EPA in the treatment of Huntington's disease are currently in progress. E-EPA does not appear to be commercially available at the present time, and it is not known whether fish oil (which contains a mixture of fatty acids including EPA) would have similar effects.

Puri BK, et al. MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment. Neuroreport 2002;13:123-126.

Mercury and fish: the good and the bad

This review article discusses the toxic effects of mercury and evaluates the risks associated with eating fish contaminated with mercury. Inorganic mercury present in aquatic sediments is methylated by microorganisms and accumulates in the food chain. A number of epidemiological studies suggest that prenatal exposure to mercury through fish consumption can damage the fetus. However, epidemiological studies of heavy fish consumers of the Seychelles Islands in the Indian Ocean have not shown adverse effects. On the contrary, the results of some developmental tests indicated beneficial outcomes that correlated with higher mercury levels during pregnancy. The authors suggest that the presence of certain beneficial nutrients in fish (including docosahexaenoic acid, choline, iodine, and iron) may have a positive effect on prenatal brain development, and that this effect may counterbalance or outweigh the adverse effect of the mercury present in fish.