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Link to fever response provides hope for hot flash relief

Women who have compared a hot flash to a raging fever may have been on to something: Hot flashes are connected to the body's fever response, scientists now believe. So will this lead to an effective treatment for hot flashes? "As a menopausal expert I'm interested in how this might help us develop potential therapies to treat hot flashes," said Dr. JoAnn V. Pinkerton, a professor of obstetrics and gynecology at the University of Virginia Health Sciences Center and a past president of the North American Menopause Society. "I can envision research coming out of this."

In the meantime, it looks like this new understanding of what links hot flashes to fever will soon provide an effective new treatment for osteoporosis.

But what, exactly, do hot flashes, bone loss and fever have to do with each other?

A new drug called denosumab reduced hip fractures in postmenopausal women by 40 percent over three years, and fractures of vertebrae by 68 percent, according to a study published in August in the New England Journal of Medicine.

It was reported in February that the Food and Drug Administration is expected to make a decision about the approval of the drug, also known as Prolia, by July.

Hot flashes, bone loss and the body's fever response are linked by a protein known as RANKL. Discovered 12 years ago, scientists quickly figured out that the protein is involved in breaking down the bones of pregnant women — a normal process that frees up calcium for the baby's bones, and triggers lactation after birth. During menopause, when estrogen declines, this process continues and can cause serious bone loss. Denosumab protects the bones because it is an antibody that inhibits RANKL.

More recently, scientists in Vienna noticed that the protein is present in the brain too. They had no idea why, but they figured they had better find out before millions of women started taking denosumab. If the drug affected the brain, that could be a problem.

Experiments showed that injecting extra RANKL directly into a rodent's brain produced a raging fever. Inhibiting the protein with another drug brought the fever down.

Also, the ability of RANKL to regulate body temperature seemed to be affected by female sex hormones produced by the ovaries — a hint that fluctuations of these proteins caused by the loss of estrogen in menopausal women would allow body temperature to spike from time to time, producing hot flashes.

Unfortunately, denosumab appears to have no impact on hot flashes.

So what else can women do?

Hormone replacement therapy certainly works, but carries with it a slightly increased risk for breast cancer, heart attack and stroke.

Antidepressants including Effexor, Paxil and Prozac have been shown to be effective at reducing hot flashes.

Clonidine, which acts on the brain to control blood pressure, has helped reduce hot flashes in some women but not others.

Soy, chickpeas and lentils contain plant-derived estrogens known as phytoestrogens, which provide relief from hot flashes for some women. Some evidence suggests that black cohosh helps some women, as does vitamin E.

Health food stores offer an array of other treatments, such as licorice, evening primrose oil, dong quai, chasteberry and wild yam, but no rigorous scientific studies prove their effectiveness.

If hot flashes are related to fever, wouldn't ibuprofen, aspirin and other medications that bring down body temperature also constrain hot flashes?

Apparently not.

"Anti-inflammatory agents improve fever but not hot flashes," Pinkerton said.

For now, women have few options for controlling flushing, overheating, racing heartbeat, night sweats and other discomforts that accompany hot flashes, but fortunately hot flashes themselves are harmless. That's why some women choose to tolerate them. Though the hot flashes may make them sweat, they simply don't sweat it.

Tom Valeo writes frequently about health matters. You may write him at tom.valeo@gmail.com.

fast facts

Help for hot flashes?

Soy, chickpeas and lentils contain plant-derived estrogens known as phytoestrogens, which provide relief from hot flashes for some women. Some evidence suggests that black cohosh helps some women, as does vitamin E. Health food stores offer an array of other treatments, such as licorice, evening primrose oil, dong quai, chasteberry and wild yam, but no rigorous scientific studies prove their effectiveness.

On the Web

North American Menopause Society: www.menopause.org

Link to fever response provides hope for hot flash relief 03/23/10 [Last modified: Tuesday, March 23, 2010 4:30am]
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