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Flush point

One minute you're cool, the next minute you're burning up. In the wake of hormone fears, scientists are seeking alternatives.

July 23, 2007|Chandra Shekhar; Rosie Mestel and Special to The Times

VIVIAN AIZAWA of Salinas vividly remembers the first time her body was hit by a heat wave out of the blue -- an episode of warmth, flushing and sweating that "almost felt like climate change," the 53-year-old says. The hot flashes and night sweats affected her sleep and strained her relationships. "It is ruining my life," she told her doctor.

Nearly three out of four women will share Aizawa's experience as they go through menopause. Many, in fact, will get hot flashes and night sweats several times a day for years, each episode lasting from a few seconds to several minutes.

"It impacts literally millions of women worldwide," says Dr. Wulf Utian, president of the Ohio-based North American Menopause Society, a nonprofit that promotes menopause research. "While not life-threatening, it is a major impediment to their quality of life."

For relief, women have tried dozens of remedies: herbs, low-fat diets, antidepressants. Then, in 1942, came a major advance. The U.S. Food and Drug Administration approved Premarin, a form of the female sex hormone estrogen extracted from horse urine. Since then, extensive studies have shown that the hormone, either alone or in combination with other sex hormones, really works: It relieves moderate to severe symptoms in 90% of women who take estrogen.

For The Record
Los Angeles Times Friday July 27, 2007 Home Edition Main News Part A Page 2 National Desk 1 inches; 62 words Type of Material: Correction
Hot flashes: A July 23 Health article on remedies for hot flashes said that a study led by Johns Hopkins Medicine researchers found that women who have hot flashes could have oversensitive serotonin receptors. The statement was a theory based on rat studies -- not a finding -- included in a review of hot flash studies written by the Johns Hopkins researchers.
For The Record
Los Angeles Times Monday, July 30, 2007 Home Edition Health Part F Page 7 Features Desk 1 inches; 61 words Type of Material: Correction
Hot flashes: An article in last week's section on hot flashes said that a study led by Johns Hopkins Medicine researchers found that women who have hot flashes may have oversensitive serotonin receptors. The statement was a theory -- not a finding -- based on rat studies included in a review of hot flash studies written by the Johns Hopkins researchers.

But hormone therapy does not suit all women; those with a family history of early breast or ovarian cancer, for instance, probably have to avoid it. And many others have concerns about long-term estrogen use, especially in the years since the landmark Women's Health Initiative trial, which reported a few years back that hormones slightly raised the risk of not only breast cancer but also heart attacks and strokes. (See "Hormones: Is age the key?")

Others are willing to take the hormone but suffer unpleasant side effects such as breast tenderness and vaginal discharges. "For these women, the cure is worse than the problem," says Dr. Nananda Col, associate professor of medicine at Brown Medical School in Providence, R.I.

And so researchers are looking for alternatives -- substances that can calm sweats and flashes while presenting fewer risks. They have identified some possible candidates -- drugs such as the antidepressant venlafaxine, the steroid tibolone and the anticonvulsant gabapentin -- and trials are underway to evaluate some of them. At the same time, scientists are gaining a better understanding of what actually causes hot flashes.

In hot surroundings, humans cool their bodies in two ways: by sweating, which dissipates heat by evaporation, or by flushing, which cools heated blood by circulating it through dilated blood vessels in the skin.

In hot-flash sufferers, both responses are often inappropriately triggered by signals from the hypothalamus, the part of the brain that regulates temperature. When this occurs, there is a discrepancy between the woman's sensation of warmth and her actual body temperature.

Old studies using thermometers placed in the mouth, ear or rectum failed to detect a temperature change during a hot flash. More recent studies, using ingested thermometers, show that there is often a core temperature change, but a small one: less than one-tenth of a degree Fahrenheit. This increase precedes 60% of hot-flash episodes.

How this tiny thermal spike could trigger such an intense feeling of warmth is less clear, though. Further, small temperature fluctuations occur even in women who don't get hot flashes. Evidently, some women tolerate body temperature fluctuations better than others.

To explain how this could be, Dr. Robert Freedman, professor of psychiatry at Wayne State University School of Medicine in Detroit, has devised the notion of a "thermoneutral zone," the range of body temperatures a person endures comfortably. It's sandwiched between a "sweating threshold," above which one feels too hot, and a "shivering threshold," below which one feels too cold.

The size of this zone in younger, non-menopausal women is about one degree, but in hot-flash sufferers it shrinks to almost zero, Freedman has found. Even a minuscule spike in temperature pushes the body over the sweating threshold, triggering a hot flash. "You've got no play in the system in these women," Freedman says.

What causes this loss of heat tolerance is still a mystery. Earlier researchers put the blame squarely on the loss of estrogen during menopause, but now scientists think that the picture may be more complex. For one thing, researchers have found no connection between a hot-flash episode and the sufferer's estrogen level at that moment. Also, there is no difference between estrogen levels of hot-flash sufferers and other menopausal women.

Finally, although estrogen is nearly 90% effective in treating hot flashes, it doesn't work for everyone. "Hormone deficiency is one factor but not the whole deal," Freedman says.

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