Flushing out the mechanism of hot flashes.

Flushing out the mechanism of hot flashes

Hot flashes plague many women undergoing menopause, sometimes striking as often as once an hour and leaving the women soaked in sweat. Though scientists know very little about what causes these unpleasant internal heat waves, a new study strengthens the case implicating certain neurons within the brain's temperature-regulating center.

Researchers have suspected that the body thermostat of women who suffer from hot flashes somehow goes awry once the ovaries cease making the female sex hormone estrogen. They reason that a loss of estrogen might somehow cause certain neurons in the temperature-regulating hypothalamus to fire abnormally, releasing norepinephrine -- a neurotransmitter believed to affect the body's temperature sensor.

Data indicate that norepinephrine elevations may create the illusion that the body had overheated, and trigger a variety of heat-loss strategies. Despite a normal body temperature, affected women might undergo a temporary flush and rush of heat as blood vessels near the skin surface dilated.

Robert R. Freedman at Wayne State University School of Medicine in Detroit and his colleagues decided to test that theory using certain drugs that manipulate the suspect neurons. They recruited 15 postmenopausal women, aged 43 to 63; six had never experienced a hot flash, nine others reported a mean of 10 a day.

To objectively measure hot flashes, the researchers wired their volunteers with electrodes hooked up to a computer system that recorded an electrical measure of sweating. Then the volunteers received a slow-drip intravenous infusion of saline from a hidden bottle. Varying doses of yohimbine, an experimental drug that boosts norepinephrine levels in the rat hypothalamus, were added to some of these infusions, but participants did not know when.

The computer recorded six flushes among the hot-flash-prone women during their yohimbine infusions. These same women developed no attacks during saline-only infusion, the researchers report in the October OBSTETRICS AND GYNECOLOGY. Previously asumptomatic women remained flush free after both the yohimbine and saline-only treatments.

Next, Freedman's team followed the lead of other researchers who had shown that clonidine, a common high-blood-pressure drug, reduced hot flashes in some women. Here, the researchers infused the same nine hot-flash-prone volunteers with either saline or a saline-and-clonidine drip infusion. After an hour, the team placed hot water pads on each subject's upper body, a procedure that reliably induces hot flashes.

The Michigan researchers found clonidine indeed decreased the number of hot flashes experienced among these women -- from eight during the saline-only infusion to just two among women receiving clonidine treatment.

These findings suggest yohimbine triggers hot flashes among susceptible women by spurring neurons in the hypothalamus to release norepinephrine, Freedman says. He now suspects clonidine may block those hot flashes by reducing norepinephrine overloads.

However, evidence on clonidine's therapeutic potential appears far from conclusive, according to Peter Lomax at the University of California, Los Angeles. Other teams using clonidine have failed to reduce hot flashes among postmenopausal women, he notes. Moreover, he points out that clonidine's blood-pressure-lowering side effect would preclude its use in many women.

Freedman and Lomax do agree, however on both the value of research into the mechanisms underlying hot flashes, and the need for new and better hot-flash blockers. Hot flashes are not trivial, but "a real problem," Lomax says. In severe cases, he notes, 10-minute-long, heart-pounding, sweat-drenching episodes can not only embarrass professional women and homemakers alike, but also interfere with their ability to perform certain critical tasks -- from driving to surgery.