Women with multiple sclerosis (MS) have long claimed that their disease seems to go into remission when they're pregnant, and that they feel better overall while carrying their babies. This was merely anecdotal until researchers at the University of California, Los Angeles (UCLA) published the results of a recent study.
Dr. Rhonda Voskuhl, a neurologist at UCLA, and her team have shown that pairing a female hormone called estriol with Copaxone, a disease-modifying therapy (DMT) used to treat MS, cuts relapse rates nearly in half with only one year of treatment.
A Winning Combination
The study divided 158 patients into two groups. One received Copaxone and estriol; the other, Copaxone and a placebo.
Relapse rates were reduced, and Voskuhl was pleased to see estriol had significant beneficial effects on cognition.
“I knew it was possible because of all the data that shows estrogen can help with cognition,” Voskuhl said in an interview with Healthline. “But it was really a pleasant surprise.”
Not every “combi” trial for MS treatment has resulted in success, however. One
“It made me think that estrogen probably works through mechanisms other than a mere anti-inflammatory,” said Voskuhl. “Interferon is a good anti-inflammatory and that didn't help with [their] clinical outcomes at all.”
“At the time that we did this study, most researchers thought it was a bad idea to have people with relapsing-remitting MS on placebo for two years,” explained Voskuhl. Until now, most of the DMTs were tested against placebo, but “those days may be gone.”
With a choice of 10 DMTs approved by the Food and Drug Administration (FDA), Voskuhl said the reason for selecting Copaxone for this study “was very calculated.”
While all of the DMTs are comparable, the time it takes them to become effective varies. Within one to three months, the interferons have been shown to cut relapse rates by up to 80 percent. Copaxone takes about six to nine months to reach its full effect.
“It seems to be as good as the others,” Voskuhl told Healthline, “but in that first year it doesn't work quite as quickly so that gives a little bit of room … where we might see an effect of adding estriol onto it.”
Many types of female hormones exist, but not all of them have been studied. According to Voskuhl, estradiol—found in birth control pills and hormone replacement therapies (HRTs)—might work, but patients can’t use a high enough dose to have the same effects that the researchers saw with estriol in this study. Estradiol can cause breast cancer, endometrial cancer, and blood clots, so higher doses wouldn’t be safe. Instead, the researchers chose to use estriol, which doesn’t have those same side effects, although estriol is not currently FDA approved.
“It's been known to be safe in Europe and Asia for decades,” said Voskuhl. "And you can push the dose of estriol up to a pregnancy level and it's still safe, whereas you'll never be able to do that with estradiol.”
Double Duty: HRTs and Birth Control as MS Protection?
According to Voskuhl, it won’t be that easy to say definitively that birth control can benefit MS patients. It would require testing an estrogen that’s safe to give at pregnancy level—like estriol. Current birth control pills contain mostly estradiol.
Whether HRTs could give dual benefit to menopausal women with MS is “a really good question,” said Voskuhl, “and a study needs to be done.” If the trial were up to her, she’d experiment with estriol in the same 8 mg dose she used for this study, or the 2 mg dose that is currently approved for menopausal women in Europe.
What About Men?
Voskuhl’s team has already completed a study in men with low testosterone that showed boosting the levels of the hormone slowed brain atrophy and had other beneficial effects, such as “improvement in muscle mass and bone density, less fatigue, and better sexual function.” She’s now submitting a trial to the National Institutes of Health that will be a multi-center placebo-controlled study that tests testosterone in men with MS.
Voskuhl believes testosterone is neuroprotective, like estriol, “because testosterone is converted to estrogen by an enzyme in the brain.” So it works the same way once it enters the brain. That means a drug tailored to gender may come in the future.
Voskuhl has filed an Investigational New Drug application for estriol with the FDA to conduct further studies. But these studies will be very costly, and her team at UCLA desperately needs funding.
“I hope a company will work with us and help us do the next study and bring it to pharmacies that are FDA regulated so everything is done the way it should be done,” said Voskuhl.
Perhaps the makers of the DMTs will see a benefit in adding estriol to their own drugs that aren't currently neuroprotective, creating an even more powerful treatment option.