There used to be a standard treatment for hot flashes and other symptoms of menopause: hormone replacement therapy. But in 2002, studies showed a possible link to cancer and what was once standard practice became a rare prescription. Since then, scientists have been searching for alternative therapies. Recently, a biochemist at UNT Health Science Center found a drug that looks promising.

Hot flashes, depression, anxiety — all these symptoms of menopause are controlled by the brain. But for decades, traditional treatment has been to flood the entire body with hormones. And sometimes, instead of solving the problem, the wave of estrogen and progestin caused an increased risk of heart disease and breast cancer.

That’s why Laszlo Prokai, a professor of pharmacology & neuroscience with UNT’s Health Science Center in Fort Worth, has been searching for an alternative. And he’s finally found a compound capable of slipping past other organs to be recognized by only the brain.

Finding The ‘Trojan Horse’

“What we found was kind of like a Trojan horse,” Prokai says. “That is manifesting not as an estrogen for the rest of the body but after getting into the brain it actually unwraps to become an estrogen, but only in the brain.”

When Prokai and his team gave lab rats the experimental drug, called DHED, estrogen levels in their brains increased, but not in the heart, uterus or breast tissue, where it can cause unwanted side effects. The results are published in the July issue of Science Translational Medicine.

The Importance Of Estrogen

Roberta Diaz Brinton of the University of Southern California’s School of Pharmacy says some women have been scared away from hormone therapy. That’s a problem, she says, because starting treatment as soon as estrogen levels drop can help avoid risks of dementia.

“The time to intervene is when the body and the brain are sending out the message that they are undergoing a deficiency in estrogen,” she says. “That can be manifested by hot flashes, or changes in cognitive function, mood, depressive symptoms.”

Diaz Brinton warns against waiting years after menopause because the brain might stop responding to estrogen.

Fine-Tuning Hormone Therapy

Like Laszlo Prokai, Roberta Diaz Brinton has been working on developing a drug to help replace estrogen with fewer side effects. Whereas Laszlo’s chemical compound targets only the brain, her team has completed clinical trials on a drug that targets the brain and bones. Why the bones? Because estrogen also plays a key role in preventing osteoporosis.

“The type of hormone therapy is very, very important, so the timing and type, and we are really moving towards personalized hormone therapy for women,” she says.

And developing personalized hormone therapy isn’t just important for women going through menopause or who have hysterectomies. Estrogen balance is also critical in men. The next step for the UNT Health Science team is to test the experimental drug on humans. And Laszlo Prokai has already created a company to commercialize the product.