Medical science has now explained hot flashes — and help may be on the way

Menopause is hot … still … again … and always, as anyone who has experienced it knows (Menopause is having a moment, and many say it’s about time – YouTube). But there may be good news on the way for women who suffer from its most common symptom, hot flashes or flushes, if new drugs that tackle the problem in a completely new way pan out.

I complained in this space back in 2016 that hot flashes were a medical mystery (Why do hot flashes remain a medical mystery? | Carolyn Brown). Fortunately for me, my hot flashes were manageable and lasted only about seven years before dissipating. For some women, they can last up to 15 years and can cause difficulty with everyday life and severe effects such as insomnia.

But there has been a scientific breakthrough since then, and we now understand why hot flashes happen. I’m going to explain it, but you might want to take a deep breath, because it’s not simple. It’s neuroendocrinology.

The reproductive cycle

The following is heavily simplified for everyday readers.

In medical terms, hot flashes are “vasomotor symptoms” — meaning they involve the blood vessels constricting and dilating. It was clear that these symptoms were tied to the drop in estrogen that happens with menopause as the ovaries stop producing this important hormone. Women who have to have their ovaries removed at a younger age than normal menopause often experience very severe vasomotor symptoms after the abrupt cut-off of estrogen.

For the following, I’ve leaned heavily on a very good review article published in the journal Neuroendocrinology in 2019 (Neurokinin 3 Receptor Antagonism: A Novel Treatment for Menopausal Hot Flushes (

Before menopause, women’s reproductive systems go through their regular monthly phases thanks to a complex process involving nerves, peptides and hormones, all acting in a delicate choreography. It starts in the hypothalamus of the brain, where specific nerves release a hormone, gonadotropin-releasing hormone. This hormone reaches the pituitary, a gland involved in growth, metabolism and reproduction, where, in turn, it stimulates the release of two other hormones, follicle-stimulating hormone and luteinizing hormone. In the first phase of the monthly cycle, the follicle-stimulating hormone controls the ovary’s production of eggs. The luteinizing hormone triggers the release of the eggs from the ovary.

These hormones also lead to the release of two other hormones — estradiol (the most potent form of estrogen) from the ovaries and testosterone from the ovaries, adrenal glands and other tissues. These hormones signal the original nerve in the hypothalamus to cease production, and hormone levels drop throughout the chain. Then the cycle starts again. This process controls women’s monthly changes in an extraordinary way without which none of us would be here.

Why menopause causes hot flashes

The big discovery is about two neuropeptides in the hypothalamus that are really key to this process — kisspeptin and neurokinin B. They are the link between estrogen and the release of gonadotropin-releasing hormone. When estrogen levels are high, these two neuropeptides lower the levels of gonadotropin-releasing hormone.

The thing is, the nerves in the hypothalamus that produce (“express”) these two peptides are in an area of the hypothalamus responsible for regulating body temperature. One of the messages from this part of the hypothalamus reduces body heat through dilating blood vessels on the skin and sweating. In hot flashes, this message is sent from the hypothalamus when it shouldn’t be.

This is a side effect of the drop in estrogen when the ovaries stop functioning in menopause. Researchers believe that the loss of estrogen means that the other hormones are not controlled and therefore increase, changing the way that the two key neuropeptides work, leading the hypothalamus to send mistaken messages to reduce body heat.

During the process, neurokinin B binds to a receptor called the neurokinin 3 receptor. If this receptor could be blocked, the hot flashes would cease.

The search for new drugs

And that’s exactly what some new drugs in development do, quite successfully, according to initial tests in women with hot flashes. Two drugs have been tested. One reduced hot flashes by 73% (45% lower than placebo), and the other, by 93% (46% lower than placebo). Unfortunately, further studies of the first drug have been halted because of concerns about risks versus benefits. Studies of the other are proceeding.

The hope is that drugs targeting the neurokinin 3 receptor can reduce hot flashes substantially with few side effects. Currently, the best treatment for hot flashes is estrogen replacement, but estrogen — especially used over many years — can increase the risks of heart disease and certain types of cancer in menopausal women. The new drugs would not increase estrogen and would therefore avoid these risks.

If you’re suffering from hot flashes right now, don’t get excited. Years of testing are needed to ensure that new drugs are safe and effective. As we have seen, one potential drug has already been shelved. It will take time, but women in their reproductive years today may have better alternatives to ease their menopausal years.

BC provincial government site publishes unsupported lifestyle advice on hot flashes

At the risk of being a one-note Johnny, I am very concerned when lifestyle advice to menopausal women from normally credible, reputable sources is unsupported by evidence, at best, or is basically old-wives’ tales, at worst. If other health information were based on such equivocal and weak evidence, it would not be considered acceptable.

The Globe and Mail recently published a lifestyle article on hormone therapy for hot flashes, which I read with interest. It mentioned that HealthLink BC, a patient health information site run by the government of British Columbia, was recommending lifestyle advice that my own literature review indicates is unsupported. By contrast, its advice on medical therapy is generally referenced and based on evidence.

This is what HealthLinkBC says:

  • Avoid using tobacco or drinking a lot of alcohol. They tend to make hot flashes worse.

The evidence on both of these is equivocal (see my previous post). There is some limited evidence from well-designed observational studies that never smoking and quitting smoking are associated with fewer hot flashes. The evidence on alcohol is mixed, with some studies showing alcohol decreases hot flashes.

  • Manage stress. Stress can make hot flashes worse.

Well, there is evidence showing that being happy and contented actually increases hot flashes and stress decreases them. There is little good evidence about effects of stress.

  • Exercise regularly, and eat a healthy diet.

As I indicated in my earlier post, the evidence on exercise is mixed and shows only modest changes. There is evidence that obesity (but not healthy weight) is associated with hot flashes, so losing weight is advisable as a way to decrease hot flashes only if you are obese.

  • Try rhythmic breathing exercises. This is called paced respiration. It can help you meditate and relax, and it may reduce your hot flashes.

OK, the first randomized controlled trial on this recently reported. There was a modest (less than 20%) decrease in hot flashes in the group that used this paced respiration method in which you slow your resting breathing rate (kind of conflicts with the exercise advice). But (get this) the control group, which listened to music instead, had a 44% decrease in hot flashes. Keeping in mind that placebo effect is huge in hot flashes, we should all be listening to music rather than breathing slowly.

  • Drink cold liquids rather than hot ones.

Hot liquids (and anything hot) can bring on a hot flash, but there is no evidence that they increase the overall frequency or severity of hot flashes.

  • Eat smaller, more frequent meals. Digesting a lot of food can make you feel hotter.

No evidence. Also, while the immediate trigger of a hot flash may be warm ambient temperature and other heat sources, the problem is not that women affected are overly hot. Menopausal women in Canada have hot flashes in minus 20 degree Celsius weather. Hot flashes do not feel like being hot from ambient temperature or exercise, and body temperature before a hot flash is normal and then actually rises measurably during the hot flash.

  • Stay cool
  • Keep your area cool. Use a fan.
  • Dress in layers. Then you can remove clothes as needed.
  • Wear natural fabrics, such as cotton and silk.
  • Sleep with fewer blankets.

Staying cool does help prevent the immediate onset of hot flashes and helps women recover from them quickly when they occur. However, from personal experience, I’m not sure it reduces the overall frequency.

No evidence.

From HealthLinkBC’s medical therapy section:

  • Black cohosh may reduce or prevent hot flashes, depression, and anxiety.

There is a reference for the paragraph containing this statement to a Health Canada page on traditional herbal use of black cohosh, which includes menopausal symptoms. There is no reference to the medical literature, which has plenty on black cohosh. There have been some small randomized controlled trials (around 300 patients) showing benefit of black cohosh in hot flashes and published in a respected, peer-reviewed journal (Obstetrics and Gynecology). However, a Cochrane systematic review pooling data from 16 randomized controlled trials involving more than 2000 women with menopausal symptoms found “insufficient evidence to support the use of black cohosh for menopausal symptoms.” However, since some studies found some benefit, the review called for more research on this traditional herbal remedy.

I find a lot of information for patients tries to get around the fact that the evidence is poor by using words like “may” or “might.” As in, “black cohost may reduce or prevent hot flashes.” Or it may not. I suspect many patient-readers looking for something to try are not going to pick up on the subtle distinction of a remedy that may or will provide some benefit. And this is concerning, as many herbal remedies are not risk-free. Black cohosh has been linked with liver-damage events in people who have taken it, although a meta-analysis of black cohosh studies found no evidence of liver problems. Black cohosh may or may not have risky side effects.

But why not just be upfront with readers about the state of the research evidence on various lifestyle advice and herbal remedies? And why tell women something is going to help when it isn’t? I also find that a lot of patient advice is good, general health advice. But it’s like health authorities are trying to trick readers into following advice by selling it as something that’s going to help with a particular problem.

There are lots of good reasons to eat properly, quit smoking and limit alcohol. Like heart disease, cancer and diabetes. Don’t tell women healthy living will help their hot flashes when it won’t.

Why do hot flashes remain a medical mystery?

It’s 3:05 in the afternoon, and I’m working at my desk when I start to get an uncomfortable prickly heat sensation. Within 30 seconds, my body temperature goes from its normal range (35.8 to 36.4 degrees Celsius) up to 36.8 degrees. My face reddens, my pulse increases from my normal 53 beats per minute to 59. I’m breathing faster and harder, and sometimes I even feel breathless. I may have to stop what I’m doing because of a sudden lack of energy. I may feel light-headed and even nauseated. At about 40 seconds in, the heat starts to subside as I break into a sweat. My skin from my scalp to my ankles is bathed in perspiration. By one and half minutes, it’s all over. But if the room is cool, the sweat may leave me feeling clammy and chilled.

Hot flashes happen day and night. On a good day, I might have about 12 hot flashes that cause only a light sweat. On a bad day, I can have more than 30 hot flashes and be so drenched in sweat that I need to change clothes and take extra showers. I’m lucky that I usually sleep through the night sweats or awaken only momentarily – many women suffer insomnia because of night sweats.

I am one member of the first generation of women to go through menopause without hormone replacement therapy (HRT), which was used to help women from the World War II to the baby boom generations avoid menopausal symptoms. Widespread use of HRT stopped after studies showed it raised the risk of some types of cancer as well as heart disease. Nevertheless, some women I know who are really suffering with symptoms are taking bioidentical hormones for a few years; it works well for some women and less well for others.

Estimates say 70% to 80% of menopausal women will have hot flashes (rates vary by country), and a recent study says they last seven and a half years on average, much longer than previously thought.

While this is mainly a women’s problem, some men also experience hot flashes as their hormone levels drop during “andropause.” My father had them during a therapy for prostate cancer that lowered his androgen hormone levels.

So, this is an almost-universal natural process. You would think that we would understand why it happens. But here’s the thing – medical knowledge really does not know why menopause causes hot flashes. For example, the Mayo Clinic website states: “The exact cause of hot flashes isn’t known.” Most medical sources explain that your estrogen level drops and then you have vasomotor symptoms, but stop short of explaining the mechanism leading from one to another. Because they don’t know.

There are a few teams working on research into the mechanism, and I’m eager to hear from them, because maybe research could shed a little light on how to cope with them.

Because there’s another ugly little fact: most of the advice well-intentioned health care professionals give to menopausal women about hot flashes has little evidence to back it up. And some of it is completely wrong.

Here is typical advice, from WebMD.

“To prevent hot flashes, avoid these triggers:

  • Stress
  • Caffeine
  • Alcohol
  • Spicy foods
  • Tight clothing
  • Heat
  • Cigarette smoke

Other things you can do to keep hot flashes at bay include:

  • Stay cool. Keep your bedroom cool at night. Use fans during the day. Wear light layers of clothes with natural fibers such as cotton.
  • Try deep, slow abdominal breathing (six to eight breaths per minute). Practice deep breathing for 15 minutes in the morning, 15 minutes in the evening and at the onset of hot flashes.
  • Exercise daily. Walking, swimming, dancing, and bicycling are all good choices.
  • Try chill pillows. Cooler pillows to lay your head on at night might be helpful.”

Let’s start with caffeine. While a 2005 study found some evidence that caffeine triggers hot flashes, a 2010 study found only a small effect of caffeine on hot flashes (this study included caffeinated sodas and cocoa). However, a very well-conducted 2011 study found that “women who drank more coffee had less severe [hot flashes] than the ones who drank less coffee.” I’m not seeing a lot of reasons to avoid caffeine, and coffee may actually help (in fact, I find that it provides short-term relief).

Which brings me to alcohol. The 2010 study found only a small effect of alcohol on hot flashes, and the 2011 study found no effect of alcohol drinking. A study just out showed that drinking alcohol during menopause actually decreased the chance of having hot flashes at all, as well as their severity. Alcohol is associated with health and social problems, so I wouldn’t start or increase drinking because of hot flashes, but there is no evidence that you should avoid alcohol if you are currently a moderate drinker.

Deep, slow abdominal breathing: This is a new approach being tested; results are not yet available. It may help cope with a hot flash. The jury is out on whether it could prevent hot flashes or make them less severe.

Anything that heats you up: Warm clothing, warm weather, warm beverages, warm food… basically anything warm can bring on a hot flash. One of my friends can get a hot flash walking by a hot stove. Keeping the room cool, turning on a fan or air conditioner, sleeping with fewer covers, etc. can all prevent hot flashes or make them less severe. But not entirely. You are still going to get them.

Tight clothing: I could find absolutely no evidence for this. The fact that women loosen or take off their clothes during hot flashes is just to get cool.

Spicy food: I found one study that came out in 2013 showing that a diet with regular hot spicy food intake increased hot flashes. The odd spicy dish might bring on a hot flash just because it warms you, but I wouldn’t cut out spicy food if it’s not a big part of your diet.

Cigarette smoke: I found mention of one study that found second-hand smoke increases hot flashes in non-smokers. More important is the evidence on smoking, which is conflicting. Observational studies have shown a negative effect of smoking, but that could be due to other positive health behaviour among non-smokers. The 2011 study, which had a strong design to detect triggers, found no effect of smoking. A new study shows that quitting smoking has a positive effect on hot flashes, making them less frequent and less severe, and that hot flashes were worse among women who had smoked than among non-smokers. Quitting smoking is a good idea for many reasons, and there is some limited evidence that it helps with hot flashes.

Obesity: Many studies have shown that obesity is a risk factor for hot flashes, so losing weight will help those who are really overweight. Women with a healthy weight should not try to lose weight to help with hot flashes – there’s no evidence for this. Furthermore, one study found that fasting (empty stomach) worsened hot flashes, and glucose improved them, so make sure you are not going hungry.

Stress: A 2005 study found that feeling happy and in control actually increased hot flashes, and stress decreased them. A small controlled study conducted in Japan and published in 2008 showed that doing a difficult mental task increased hot flashes on the spot. A recent study found that greater perceived stress and more depression and anxiety symptoms when hot flashes started were associated with more years of hot flashes. However, these stress symptoms may be an effect rather than a cause, and depression and anxiety are also symptoms of menopause itself. Limiting stress is a good idea for lots of reasons, but it’s unclear whether it helps with hot flashes. And I’m not going to stop doing difficult mental tasks because they might cause hot flashes.

Exercise: A very good randomized controlled trial published this year showed that exercise had no effect on hot flashes. A previous study showed that exercise actually worsened hot flashes, unless it was intensive exercise, in which case it improved them. Exercise is good for your general health, and there are lots of reasons to get exercise, but it probably won’t help with hot flashes.

The problem with trying to study hot flashes is that there are strong placebo effects – basically, if you think something might help, it probably will, but it seems to be mind over matter. And hot flash frequency and severity change often during menopause, sometimes day to day, so it’s difficult to say that doing any particular thing affected hot flashes. That’s why anecdotal reports from women that something improved their hot flash experience are unfortunately unreliable. The lifestyle advice has very little evidence behind it, except for losing weight if you are obese and for quitting smoking. Help for hot flashes will come from basic research into what causes them – I’m waiting for that news.