In a pilot study at UCLA, women took Trimesta, a synthesized form of estriol used in Europe and Asia for treating hot flashes. They showed an 80 percent reduction in M.S.-related lesions on the brain within three months of treatment. After six months, their cognitive function improved by 14 percent.
    Now the Pipex Pharmaceuticals drug is being studied at the University of Utah and six other sites in the country in a three-year, Phase II clinical study.
    About 150 women with relapsing-remitting M.S. will participate, half of whom will be injected with Copaxone - a common drug therapy for M.S. - and take placebo pills, while the other half will receive the injections plus estriol pills.
    "We're very excited about this trial because we think it will be a completely new direction for women with M.S.," said John Rose, chief of neurology at the VA Medical Center and a professor of neurology at the U. "The mechanism of action of the drug looks to be very gentle, b ut potentially very effective."
    During pregnancy, Rose said, women experience a shift in their immune system, from cells protecting them from disease to antibodies taking on the role. The change works to the advantage of M.S. patients, whose cells secrete proteins that trigger an autoimmune response.
    Estriol, it is believed, may play a role in this change in immune repose.
    The goal of the study, said Rhonda Voskuhl, a professor of neurology at UCLA, is to see if estriol leads to a reduction in relapses, disabilities such as fatigue and depression, and brain atrophy. She's also eager to see if it leads to better "neuroprotection," reducing the ability of immune cells to attack the brain while at the same time making it more resistant to damage.
    Voskuhl, the overall principal investigator, showed in her pilot study that estriol stimulated cells to rebuild the brain's protective coating of myelin, a fatty nerve-insulating protein that's typically worn thin or disintegrated by M.S. The resulting neuron inflammation leads to the formation of lesions or plaques on the brain.
    Voskuhl said interest and research in estriol was in part stimulated by the National Multiple Sclerosis Society's creation of a task force to explore gender and M.S.
    "The National MS Society recognized in 1997, as a field, that it is very fertile to discover new suppressive mechanisms," she said.
    On the horizon, Voskuhl said, are larger studies to explore how testosterone may reduce M.S. symptoms in men. The hormone is already used to prevent muscle wasting in male HIV patients and cognitive degeneration in the elderly.
    One pilot study conducted by Voskuhl showed that testosterone - which converts to estrogen in the brain - may also have a measurable impact on M.S. symptoms in men, though not to the extent estriol does in women, she said.
    "We showed improvement in cognition and also slowing of brain atrophy," she said.
    Added Rose, "All of these hormones have many different analogs. It could be that something a little bit special will have an impact, but I don't know we'll have . . . an equivalent right away."

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