A new drug promises hot flashes due to menopause

A new treatment for hot flashes has brought relief and a better night’s rest to women who experience these devastating symptoms during menopause.

Two phase 3 clinical trials compared the drug elizanetant with a placebo at two time points. The drug quickly eased hot flashes: By the fourth week, most of those taking the drug reported at least a 50 percent reduction in frequency.

By week 12, more than 70 percent of those taking elinzanetant, compared with more than 40 percent on placebo, experienced that decrease in hot flash frequency, researchers reported Aug. 22 in. Journal of the American Medical Association. Participants on elinzanetant also reported significantly improved sleep compared to those taking placebo at the 12-week mark.

“Elinzanetant is a promising new nonhormonal treatment,” says Talia Sobel, a women’s health internist specializing in menopause at the Mayo Clinic in Scottsdale, Ariz., who was not involved in the trials.

After the first 12 weeks, the trials switched placebo users to the drug. Studies of treatments for hot flashes often show a placebo effect, says JoAnn Pinkerton, a gynecologist specializing in menopause at the University of Virginia Health System in Charlottesville. This may be due in part to the therapeutic rituals of trials, the researchers have proposed.

“We wanted to see if there was an additional effect beyond the placebo,” says Pinkerton. “And indeed, there was.” At week 26, 82 percent of participants who took elinzanetant throughout, and more than 84 percent of those who switched from placebo, reported at least a 50 percent reduction in hot flash frequency. The finding that more than 80 percent of all participants benefited, regardless of whether they started or switched to the drug partway through the trial, “is pretty dramatic,” Pinkerton says.

In menopause, which signals the end of ovulation and menstruation, ovarian production of the sex hormones estrogen and progesterone fluctuates and eventually stops. During menopause and for years afterward, people can experience a variety of severe symptoms, including hot flashes, night sweats, restless sleep, mood swings, loss of concentration, vaginal dryness, and urinary urgency.

Up to 80 percent of women experience hot flashes at some point during the menopausal transition, and symptoms can persist for many women for more than seven years. Hot flashes are thought to be due to a narrowing of the range of sensitivity to body temperature, such that a small rise in body temperature can be felt as a flash of heat. The body’s exaggerated cooling response can cause excessive sweating and a flushed appearance from dilated blood vessels.

Hormone therapy—estrogen with progesterone or estrogen alone—is the most effective treatment for hot flashes and menopausal symptoms affecting the vagina and urinary tract.SN: 1/9/18). The North American Menopause Society reaffirmed in 2022 that, in the absence of certain health conditions, hormone therapy is a safe choice for women who are younger than 60 or who begin therapy within 10 years of the onset of menopause. Hormone therapy also protects against bone loss, which occurs as estrogen declines with menopause.

There is also a need for non-hormonal treatments. For women older than 60 or those more than 10 years past menopause, hormone therapy is associated with a higher risk of coronary heart disease, stroke, and blood clots. People who have had estrogen-sensitive breast cancer, previous blood clots, a history of stroke, severe endometriosis and migraines with aura are among those who would not be good candidates for hormone therapy, Pinkerton says.

Research focused on a group of neurons in the hypothalamus – called KNDy neurons – that are involved in temperature regulation, has led to the development of new non-hormonal treatments for hot flashes. As estrogen levels drop, these neurons grow and become overactive, which stimulates the production of certain chemical messengers. One of the messengers binds to a receptor found on KNDy neurons and nearby thermoregulatory neurons that appears to trigger hot flashes.

A drug called fezolinetant, which blocks that receptor, received approval from the US Food and Drug Administration in 2023. The new drug, elinzanetant, targets the same receptor but also interferes with another receptor displayed by neurons NCDs that may play a role in insomnia.

Participants in the two phase 3 clinical trials for elinzanetant were postmenopausal women 40 to 65 years old who had 50 or more moderate to severe hot flashes in a week. Headache and fatigue were the most common side effects reported by participants taking the drug compared to those taking placebo. There is a 52-week trial of elinzanetant evaluating long-term safety, while another trial is looking at how well the drug works for women receiving therapy for hormone-positive breast cancer (SN: 5/3/23).

Many women who experience hot flashes and other troubling menopausal symptoms aren’t getting enough or appropriate treatment, Sobel says. “There are safe and effective options, both hormonal and non-hormonal, that can help improve their symptoms and quality of life…I encourage women to find a trusted clinician who is trained in menopause management .”