Re: Estriol may ease MS---RACHEL!

January 8, 2008

This is probably why women who are pregnant feel so much better if

they have an autoimmune disease...and after birth, their symptoms

return.

RACHEL....I hope you are seeing this!!!! How are you? when are you

due?

Patty

>

> http://www.neurologyreviews.com/nov02/nr_nov02_estriol.html

>

> ESTRIOL MAY EASE RELAPSING-REMITTING MS IN WOMEN

> BALTIMORE—Administration of oral estriol, the predominant

estrogen of pregnancy, to nonpregnant women with relapsing-remitting

multiple sclerosis increased protective immune responses and

decreased the number and volume of gadolinium-enhancing lesions on

monthly cerebral magnetic resonance imagings (MRIs), a phase I study

has shown.

> " To our knowledge, this is the first time a pregnancy hormone has

been given at a pregnancy dose to [patients] in an attempt to

ameliorate a putative Th1-mediated autoimmune disease by using highly

sensitive subclinical markers of disease activity as an indicator, "

reported Rhonda Voskuhl, MD, and colleagues in the October ls of

Neurology. Dr. Voskuhl is Associate Professor of Neurology at the

Geffen School of Medicine at the University of California, Los

Angeles (UCLA).

> " This novel treatment strategy of using pregnancy doses of

estriol in multiple sclerosis has relevance to other autoimmune

diseases that also improve during pregnancy, " the authors noted,

including rheumatoid arthritis, uveitis, thyroiditis, and a number of

other arthritides.

> HORMONES AND MS

> Two widely accepted clinical observations implicate hormones in

multiple sclerosis. First, " women are clearly more susceptible than

men to multiple sclerosis; second, women with multiple sclerosis

improve transiently during pregnancy, " particularly during the last

trimester, said Dr. Voskuhl at the 7th Annual Meeting of the Americas

Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS)

and the 18th Congress of the European Committee for Treatment and

Research in Multiple Sclerosis (ECTRIMS).

> Estriol, produced by the fetal placental unit, is not detectable

at appreciable amounts until pregnancy, when it progressively

increases. Previous studies have found that estriol administered to

mice with experimental autoimmune encephalomyelitis resulted in

amelioration of multiple sclerosis, with a favorable shift in immune

response similar to that seen during pregnancy.

> Dr. Voskuhl, who is also a research scientist at UCLA's Brain

Research and Neuropsychiatric Institutes, explained that estriol at

pregnancy doses has been given in Europe and Asia in the form of

hormone replacement therapy for symptoms of menopause, " which means

we didn't have to reinvent the wheel on assessing toxicity. It was

very well known how this estriol preparation would be tolerated.

Therefore, we could go straight to a phase I clinical trial focusing

on multiple sclerosis–related disease measures. "

> Noting that all currently available anti-inflammatory therapies

for multiple sclerosis are injections, Dr. Voskuhl reported that the

purpose of the trial " was to test a noninjectable, oral anti-

inflammatory hormonal treatment " in an attempt " to recapitulate the

beneficial effect of pregnancy. " The study included a six-month

baseline pretreatment period, six months of treatment with oral

estriol 8 mg/d, and a six-month posttreatment evaluation period.

Patients with relapsing-remitting multiple sclerosis received an

additional four months' retreatment with oral estriol 8 mg/d with

progesterone, she added.

> Twelve women with clinically definite multiple sclerosis were

included in the study; six with relapsing-remitting and six with

secondary progressive disease. Patients were excluded if they had

been taking interferon-beta or glatiramer acetate for six months or

steroid therapy for three months prior to enrollment.

> " We did an MRI every month throughout—we followed them in the

clinic every three months, " Dr. Voskuhl said. A delayed-type

hypersensitivity (DTH) response to tetanus and candida was performed,

once in the pretreatment period and once in the treatment period, as

was Paced Auditory Serial Additional Task (PASAT) cognitive testing.

> All six patients with relapsing-remitting multiple sclerosis and

four with secondary progressive multiple sclerosis completed the

study. One patient was disqualified because of concurrent steroid

treatment " and the other did not wish to go untreated in the

posttreatment period, " the investigators noted. Mean age of those who

completed the study was 44 years (range, 28 to 50). For all patients,

mean Expanded Disability Status Scale score was 3.3 (range, 1.0 to

6.5); for those with relapsing-remitting disease it was 2.2 and for

secondary progressive, 5.0.

> ENHANCING RESULTS

> Compared with the six-month pretreatment baseline period, the

total volume and number of enhancing lesions for all 10 patients

decreased during the treatment period, the investigators found, with

cognitive improvement seen entirely in the relapsing-remitting group.

In this group, median total enhancing lesion volumes decreased by 79%

and number of lesions by 82% within the first three months. Over the

next three months, lesion volumes decreased by 82% and numbers by 82%.

> During the six-month posttreatment period, " median total

enhancing lesion volumes and numbers became variable in the first

three months off treatment, before returning to near-baseline levels

in the last three months, " the researchers remarked.

> Patients retreated over four months had a decrease in enhancing

lesion volumes of 88% and in numbers of 48% compared with original

baseline scores. " Changes in median new enhancing lesion volumes and

numbers followed similar patterns as median total lesion numbers and

volumes, " they observed.

> For the entire group, median T2 lesions were 15.3 cm3 (range, 6.1

to 33.8); no significant differences were seen between the two

subgroups. In the relapsing-remitting group, median T2 lesion volumes

showed no change during the six-month treatment period, a 7.4%

increase during the six-month posttreatment period, and a 2.0%

decrease in the four-month retreatment period.

> After six months of estriol treatment, patients' DTH responses to

tetanus decreased significantly compared with month 3 (pretreatment

baseline), whereas responses to candida " were decreased less

drastically and more variably, " the researchers found. In relapsing-

remitting patients, interferon-gamma levels were significantly

decreased after six months of treatment compared with baseline. No

decrease was seen in the patients with secondary progressive disease.

Similarly, in the relapsing-remitting group, PASAT cognitive testing

scores improved significantly and no change was seen in the secondary

progressive group.

> During treatment and retreatment, serum estriol levels

approximated " those observed in women who were six months pregnant

but were lower than those who were 8.5 months pregnant, " the authors

wrote. Few relapses were observed during the study, and the estriol

was found to be well tolerated.

> Since the study was submitted for publication, Dr. Voskuhl

reported that additional immunologic studies performed on the six

patients with relapsing-remitting disease showed an increase in IL-5

and a decrease in TNF with estriol treatment. A double-blind placebo-

controlled study is now being planned in patients with relapsing

remitting multiple sclerosis only, with the goal " to reproduce what

we did in the pilot—that is, to get a decrease in gadolinium-

enhancing lesions, a favorable shift toward cytokine production, and

an improvement in PASAT, " Dr. Voskuhl concluded.

> NR

>

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January 8, 2008