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If you're among the 75 percent of women who experience hot flashes during perimenopause, you're probably used to peeling off clothes and perpetually adjusting the thermostat. Given all the bad news about hormone therapy, we're lucky that a small community of researchers (including Robert R. Freedman, PhD, the director of the Behavior Medicine Laboratory at the C.S. Mott Center and a professor of ob/gyn at Wayne State University in Detroit, whom we interview here) has long been looking to develop a fuller picture of what causes hot flashes -- and what remedies really bring relief. Read on for surprising news.
Q. How on earth did you end up studying hot flashes? A. "About twenty years ago, a graduate student who had read my research on using biofeedback to treat Raynaud's disease [a condition that causes blood vessels to constrict, limiting blood flow] came to me and said, 'You've taken cold women and made them warm. Can we do the opposite?' His mother had breast cancer, so she couldn't take hormone therapy. So this kid got me started."
Q. Was there any other research back then? A. "Not much. Even today, only a handful of scientists in the country are studying hot flashes. Probably the first important paper, which was published over twenty years ago, was by Samuel Yen, an endocrinologist then at UCLA. It showed that seventy percent of hot flashes recorded in the laboratory corresponded with LH pulses [leutinizing hormone, which is produced in the pituitary gland and involved in ovulation and menstruation]. People worked on the theory that LH pulses were the trigger for five to ten years, until another group at UCLA disproved it."
Q. What do you think causes hot flashes? A. "My guess is it's a combination of aging, and estrogen withdrawal affecting hermoregulation in the brain. Estrogen withdrawal is necessary, but not alone responsible, for hot flashes to occur. We do know that norepinephrine levels are higher in the brains of women who have flashes compared to women who don't. Estrogen withdrawal has been linked to elevated brain norepinephrine levels in several animal and a few human studies. "The master temperature control in your body is probably in the hypothalamus, and it's affected by norepinephrine. The hypothalamus is like your living-room thermostat, which has a neutral zone in which neither the air conditioning nor heating system is turned on. It's the same in the body. Everyone has a thermoneutral zone -- the span between the upper threshold, at which sweating occurs, and the lower threshold, at which shivering occurs. In women who don't get flashes, the neutral zone is about .4 degrees centigrade wide, which means they have a lot of play. But in the flashers, it's almost zero -- probably because increased norepinephrine, possibly brought on by reduced estrogen, has narrowed the zone. Hot flashes occur when small elevations in core body temperature cause a rise that's above this small neutral zone."
Q. What's actually happening in the body during a hot flash? A. "The hypothalamus likely gets information that body temperature is going up. As soon as the sensor detects that a woman's body temperature is above the threshold for sweating, she'll sweat, mostly on the upper body (from the sternum up). Almost at the same time, there is peripheral vasodilation in your hands, arms, feet, legs and face. The combination is what causes flashing."
Q. Is there any benefit or downside (besides temporary discomfort) of having a hot flash? A. "Nope, nothing that we can think of. We're almost done with a sleep study, and the latest results show that flashing and nonflashing postmenopausal women, and even premenopausal women, all sleep about the same."
Q. How do you measure hot flashes? A. "We have three temperature- and humidity-controlled laboratory rooms, with beds and reclining chairs. Each patient is connected to a polygraph, which records physiological data, including heart rate, sweat rate, skin temperature, and rectal temperature. In most studies, we also measure core body temperature by having subjects swallow a telemetry pill, which measures core temperature about every thirty seconds and reports the information to a small recorder (worn on a belt) until the pill is excreted."
Q. If a woman volunteers to have her hot flashes studied in your lab, what can she expect? A. "A standard study involves a group of postmenopausal woman with flashes and a group of postmenopausal women who have never had them. The latter is extremely hard to find. Subjects definitely are not on hormones. "Patients change into scrubs. Then the research assistant will put four little metal disks [thermistors] on their skin to measure temperature. The patient will also insert one herself, in her rectum, and swallow a telemetry pill. Other wires are attached to the body to measure heart rate, as is a plastic gadget we designed that fits over the chest to measure sweat rate. "For night experiments, patients sleep for three to four nights at their regular bedtimes. Sometimes, after night two, they stay through the afternoon and we give them a napping test; we see how fast they fall asleep to determine how sleepy they are."
Q. Do you wait for hot flashes to occur naturally, or can you trigger them? A. "We do it both ways. To trigger them, we raise the room temperature to 26° centigrade [78.8° Fahrenheit], and we put two special heating pads, which have water circulating through them at a temperature of 42° centigrade [107.6° Fahrenheit], on them."
Q. Have these experiments yielded any helpful information? A. "One of the important things we found is that women with flashes sweat at a lower body temperature than women without flashes, so it's easier for them to sweat at a given temperature; and they also sweat twice as much as the nonflashers."
Q. What are some of the worst-case scenarios you've encountered? A. "The normal duration of a hot flash is about five to fifteen minutes. The worst case I saw was a woman who, based on her physiological readings, had a flash that lasted an hour. You need to have at least six flashes a day -- that's a little on the high side for the general population -- to be admitted to our studies. But I have seen a handful of women in the lab who get as many as twenty-four in one day -- about one an hour. You often see that in women who are on tamoxifen. I suspect it's because the estrogen receptors relevant to thermoregulation are being blocked by the antagonist properties of tamoxifen."
Q. What can women do to mitigate symptoms? A. "Anything that cools you down -- cooling towels, drinking ice water -- is good. Yoga breathing is also very helpful; it's as effective as some medications are during the day. The problem is, you can't do it while you're sleeping. We're still not sure how it works: We measured several indicators of sympathetic nervous system activity, and the results weren't due to the effect of breathing on that system."
Q. Do you still recommend that women take hormone therapy for the short term? A. "Ultimately, it's up to the patient. I'm a PhD, not an MD, so I've never prescribed it. But I've stopped recommending it. Women who have chosen HT will typically find that their symptoms return when they go off it. Tapering off slowly might help."
Q. Don't hot flashes stop a year after menstruation has ceased? A. "No. At this time, we don't know what makes them stop when. There are even a few women in their 70s who are still having them."
Q. Besides hormone therapy, what other options exist? A. "Clonidine, a blood-pressure medication, is one, but the side effects can be bothersome. It makes you tired and gives you a dry mouth, plus women who have low blood pressure to begin with can't take it. I tried it myself to see what it was like, and I didn't like it one bit."
Q. Are any herbs useful? A. "My opinion is that none of the herbs work. There have been at least a dozen major soy studies, and the results have been disappointing. Black cohosh, red clover.... So far nothing really seems to be effective."
Q. What about antidepressants? A. "If I really wanted a pharmacological treatment, I would consider it. All of the studies have been on Effexor and Paxil, and they seem comparable. There is zero data explaining how these work for hot flashes. A lot of animal data show that norepinephrine and serotonin work in opposite fashion. So my theory is that if you boost serotonin -- which is what these antidepressants do -- you widen the thermoneutral zone."
Q. Should women consider gabapentin, an antiseizure drug? A. "It's a maybe. There have been two pilot studies, and one larger study showed that it reduced hot-flash frequency about fifty percent. There's no obvious research pathway -- I can't imagine how it works."
Q. Do you expect any big breakthroughs soon? A. "Ultimately, we're trying to find out the definitive cause of hot flashes. We know that they're triggered by temperature fluctuations in a narrow thermoneutral zone, but the question is, do these fluctuations arise over time, or do you always have them? It's rare, but some much younger women have flashes during their menstrual period, after the preovulatory surge of estrogen. We know their hormone levels spike and then plummet quickly enough to cause a flash. "To get a better understanding of how and when temperature fluctuations arise, we've just started studies on younger women. In general, they have thermoneutral zones that are similar in range to the postmenopausal nonflashers. We're taking about a dozen premenopausal women, a dozen postmenopausal women with flashes, and a dozen postmenopausal women who have never had flashes, and having them swallow the telemetry pills, measuring their thermoneutral zones -- the whole thing. We would be surprised to see the menstrual women flash, but we're studying them to learn more about temperature fluctuations. Preliminary results will be available in one year."