A safer estrogen therapy for women?
Scientists have found a way to boost estrogen only in the brain, a success in rats that may translate to safer treatments for people.
“This could be very applicable for women suffering from hot flashes or depression for whom estrogen therapy is really counter-indicated,” says neuropharmacologist Roberta Brinton of the University of Southern California in Los Angeles, who was not involved in the new work.
Researchers led by biochemist Laszlo Prokai of the University of North Texas Health Science Center in Fort Worth were studying the production of estrogen in the body when they realized that one estrogen-generating pathway was only active in the brain. A compound called 10β,17β-dihydroxyestra 1,4 dien-3-one (DHED), they found, relies on an enzyme in the brain to be converted from its “prodrug” form into the active form of estrogen; other organs in the body use different starting blocks to generate the hormone. That means that, theoretically, treating animals with DHED would only result in an estrogen increase in the brain, not in the heart, uterus, or breast tissue, where it can cause unwanted side effects.
And indeed, when the researchers gave rats doses of DHED, estrogen levels in their brains increased, whereas levels elsewhere in the body remained stable. What’s more, in female rats lacking ovaries—prone to hot flashes, depression, memory problems, and stroke—DHED reversed these nervous system–linked menopause symptoms without any detectable impacts on the rest of the body, the scientists report online today in Science Translational Medicine.
“Because this prodrug remains completely inactive everywhere else in the body, you can remedy the neurological and psychiatric symptoms associated with estrogen deficiency while avoiding side effects in the rest of the body,” Prokai says.
Science| DOI: 10.1126/science.aac8891
