Do Antihistamines Work for Hot Flashes in Menopause?
Tackling one of the latest claims
Recently, several people sent me an Instagram post about antihistamines, specifically Zyrtec, possibly being a “cure’ for hot flashes. Apparently, there was some new research, and a study was cited to support the claim.
Here’s the TL;DR (too long; didn’t read) version: no, there is no good data supporting Zyrtec, or antihistamines in general, for hot flashes in menopause. This is the reason it is not listed in the 2023 Menopause Society Guidelines for non-hormonal therapies. If you don’t need or want to know more, that is totally fine! But as it took quite a lot of research and reading to get to the TL;DR, I thought it was worth sharing the full meal deal for those who want to know more.
My First Impression
When a common medication is recommended as being very effective (as the word cure implies) for any condition or symptom, this should be, well, common knowledge. There are, after all, no secret cures. If a therapy is really effective, especially a readily available over-the-counter therapy, it doesn’t stay secret! So, I was immediately skeptical as I couldn’t remember seeing good evidence for antihistamines in any guideline, and if a new study were coming out that dismantled everything we thought we knew about hot flashes, showing antihistamines were THE THING, I like to think I would have heard about it! It wasn’t mentioned at The Menopause Society Meeting in September, and my Google search for a new study turned up a blank.
Another concern for me was the suggestion of a “cure.” This isn’t a word that should be used lightly. We don’t cure hot flashes; we treat them. A cure implies you take a course of medication or have surgery or radiation, and then you are, well, cured and don’t need it anymore. Treatment typically means if you stop the therapy, the symptoms and/or condition may return, for example, medications for high blood pressure or estrogen for hot flashes. The word cure sets up false expectations, and it could lead some people to make a leap and wonder if doctors are misinformed about effective therapies that exist right under their noses.
And let’s be real. Estrogen is the gold standard for hot flashes, and it does not make 100% of hot flashes go away for 100% of people, and it most certainly isn’t a cure. I get that people use hyperbole on social media, but I find it problematic when talking about medical therapies. Hyperbole is not part of informed decision-making.
With those two concerns tucked away in the back of my mind, I proceeded to look at the claim.
The Reference
The post claimed there is “new research” and supports that claim with this reference: Ramos C, Amato P, Sangi-Haghpeykar Y, et al. Cetirizine (Zyrtec) in the management of hot flashes in postmenopausal women: a randomized controlled trial. Menopause 2003;10:596.
A 20-year-old study is not new, but we’ll put that to one side as an annoyance and not a major concern. After all, if the data is solid, it doesn’t matter how old or new.
A randomized controlled trial and in a quality journal, Menopause, indeed sounds promising. But this is not a research paper that has passed peer review; it is a published abstract, which is a summary of research presented at a conference (we’ll get to why that matters shortly). I could not track down the abstract to read it myself because it doesn’t appear to have been digitally archived by the journal. The abstract should be on page 596 of volume 10 from 2003, but when you pull the table of contents from that volume and year, pages 559-610 are missing. The logical explanation is that when the back issues of the journal were archived, the conference abstracts were not included for whatever reason (oversight, cost, who knows?). But this means the abstract is only available to someone with a hard copy of volume 10 of the journal Menopause from 2003. And all my sources for a hard copy turned up dry.
Undeterred, I took to Twitter (no, I do not recognize the new name) and was able to contact one of the authors, Dr. Amato, but unfortunately, she did not have a copy of the abstract (I, too, do not have any information on abstracts that I wrote 20 years ago!).
All I can tell you about the study is that it was a four-week trial of cetirizine, 10 mg a day for hot flashes, and that hot flash scores reduced from 39.7% vs 8.8%. That information comes from a story in OB/GYN News that covered the conference when the abstract was presented in 2003.
I confirmed with Dr. Amato that this abstract was not later published as a full study in a peer-reviewed journal. This is important because an abstract at a conference is not peer-reviewed like a publication. It doesn’t mean anything bad about the abstract, only that it wasn’t turned into a full publication. Lots of abstracts get presented at meetings and then don’t get published as full articles for all kinds of reasons.
What is important is that we don’t base treatment decisions on abstracts presented at meetings; we need to wait for the full publication because abstracts leave many unanswered questions. Some of the unanswered questions I would want to see answered in a paper are what happened after four weeks? Cetirizine can be sedating for some people, so how many knew they were taking an active medication? The placebo response was quite low, so how was that explained? It’s okay that I don’t have these answers because an abstract at a meeting isn’t meant to answer all the questions; that is what the full peer-reviewed publication does.
In fact, at this year’s Menopause Society meeting, one author who presented a very interesting abstract asked us not to write about it because the full statistical analysis was not yet complete, so their conclusions could possibly change. I was totally bummed because it was really exciting, but it was a good reminder that abstracts don’t represent the completed work.
The important takeaway here is four weeks of data from a conference abstract is interesting and hypothesis-generating and might lead someone to investigate this in other studies, but this is not the basis for treatment recommendations.
Do Antihistamines Help Hot Flashes?
Is there any other work here?
I can’t find any published peer-reviewed clinical trial showing a benefit from antihistamines for hot flashes. I did find one study from 2011 that showed cinnarizine, which is also an antihistamine (that also has other properties), was ineffective at treating hot flashes. I am fairly confident that I haven’t missed anything significant, as antihistamines aren't mentioned in the 2023 Menopause Society Guidelines for non-hormonal medications; it appears they didn’t even make the cut to discuss the quality of the data.
The European Menopause and Andropause Society (EMAS) 2015 guidelines also don’t mention antihistamines as a treatment option, and neither does a 2016 guideline from the Australasian Menopause Society (AMS). Although an AMS fact sheet from 2017 states, “Small studies have shown that a widely available antihistamine (cetirizine) might help some women with menopausal symptoms. At this stage, more research is needed to confirm this is a future treatment option.” I can’t find these small studies, and there are no references listed. I personally wouldn’t include a conference abstract as a study, but others might feel differently. Regardless, “more research is needed” isn’t in the same universe as a cure.
Could Antihistamines Help Hot Flashes?
The original study was designed because one of the authors thought that patients who were starting antihistamines said they were having fewer hot flashes. That is a good basis for a study, especially as histamine is an important neurotransmitter in the brain. Histamine plays a role in the control of body temperature, the cardiovascular system, and stress-triggered responses, so it is biologically plausible that histamine could have a role in hot flashes. However, cetirizine doesn’t cross into the brain as well as other older antihistamines (the ones that can make you super drowsy), so the idea that it would be effective working at the level of the brain for hot flashes is questionable. But that is why we study things; sometimes, we are surprised by the results! If there were an appropriate peer-reviewed study that ran with the hypothesis from 2003 and showed cetirizine worked for hot flashes, I’d gladly accept it.
Another way medications can work on hot flashes is outside of the brain, on sweat glands, and the blood vessels that dilate in the skin. However, most research suggests the sweating and flushing of a hot flash are primarily controlled at the level of the skin by the neurotransmitter acetylcholine. This is likely one of the ways that the nonhormonal medication oxybutynin works for hot flashes, as it blocks acetylcholine. The biology of hot flashes is poorly understood (they are incredibly complex), so could histamine affect sweat glands and/or blood vessels, and we don’t yet know? I am open to whatever good science can tell me, but right now, we don’t have that data.
Histamine can also stimulate estrogen production in the follicles (in work done in a lab), but this would speak against an antihistamine being useful for hot flashes.
Estrogen can magnify skin reactivity to histamine. We know this because when allergy testing is done, research suggests the most pronounced response coincides with ovulation which is when estrogen levels are at their highest. Basically, if something is going to give you an allergic reaction or make you itch, biologically, your response could be worse mid-cycle when estrogen levels are higher. During the late menopause transition, estradiol levels can sometimes be higher even than in a typical cycle, so if you are someone with allergies or eczema, you could theoretically have more reactions of flares at times during the menopause transition. If that is happening to you, an antihistamine might be helpful. But here, an antihistamine is not being used for hot flashes.
Is it possible that the ups and downs of hormones in the menopause transition might result in histamine changes that we have yet to know about because they are unstudied? Sure, but that would be just a hypothesis, and people deserve more than unstudied hypotheses.
Pharma is well acquainted with antihistamines, and my completely unproven hunch is if these medications were very effective for hot flashes, it’s almost certain Pharma would be developing a new “better” and much more expensive prescription antihistamine that was actually just an older antihistamine that was off patent with a minor tweak to get a new patent. But that’s a hunch and possibly even bordering on conspiracy theory thinking (I need to be mindful of that!).
Summary
And now you know how I go about researching these claims. A good shortcut for those interested in looking into claims themselves about nonhormonal medications is to see what The Menopause Society guidelines have to say (the link is below in the references). And, of course, you can always ask here in the comments, and I will gladly fall down a few rabbit holes.
When I Googled “antihistamines and hot flashes,” some of the hits were about histamine intolerance. It took a little bit of digging to find information from evidence-based sources, so after I’d done a TON of reading that really had nothing to do with the original question, I felt compelled to write up a summary that you can find below after the references. This is a bonus for subscribers, but it is not needed to answer the original question about hot flashes.
Is there anything wrong with trying cetirizine for hot flashes? In general, it’s a safe medication, and as long as it doesn’t make you sedated, interfere with your day or driving, or react with medications you are already taking, probably not. Just keep in mind that the placebo response with medications for hot flashes is pretty high.
While we don’t think histamine is a big driver of hot flashes, it’s a largely untested hypothesis, and we don’t know what we don’t know, so I am always open to what new research might tell us. In fact, I think it’s a privilege to get paradigm-shifting results. Being proven wrong is a joy because it means we have learned something new, and in this case, something that could help people. But as of now, there is no quality data supporting the use of antihistamines for hot flashes due to the menopause transition or menopause.
References
The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023 Jun 1;30(6):573-590. doi: 10.1097/GME.0000000000002200. PMID: 37252752.
OB/GYN News, Nov. 1 2003. https://www.thefreelibrary.com/Zyrtec+may+reduce+hot+flashes+in+postmenopausal+women%3A+small+trial.-a0110804576
Cezarino PY, Bagnoli VR, Fonseca AM, Soares JM, Baracat EC. The effects of cinnarizine on menopausal symptoms in women. Climacteric. 2011;14:492–6.
Mintziori G, Lambrinoudaki I, Goulis DG, Ceausu I, Depypere H, Erel CT, Pérez-López FR, Schenck-Gustafsson K, Simoncini T, Tremollieres F, Rees M. EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms. Maturitas. 2015 Apr 22. pii: S0378-5122(15)00649-0. doi: 10.1016/j.maturitas.2015.04.009.
Australasian Menopause Society, Non-Hormonal Treatments for Menopasual Symptoms 2016, Information Sheet. https://www.menopause.org.au/images/stories/infosheets/docs/AMS_Nonhormonal_Treatments_for_Menopausal_Symptoms.pdf
Australasian Menopause Society Fact, Non-Hormonal Treatments for Menopasual Symtpoms. Fact Sheet 2017 https://www.menopause.org.au/health-info/fact-sheets/non-hormonal-treatment-options-for-menopausal-symptoms
Haas HL, Sergeeva OA, Selbach O. Histamine in the Nervous System. Physiological Reviews 2008;88:1183-1241.
Lundius EG, Sanchez-Alavez M, Ghochani Y, Klaus J, Tabarean IV. Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons. J Neurosci. 2010 Mar 24;30(12):4369-81.
Bódis J, Tinneberg H-R, Schwarz H, et al. The effect of histamine on progesterone and estradiol secretion of human granulosa cells in serum-free culture, Gynecolog Endocrin 1993;7:235-239, DOI: 10.3109/09513599309152507.
Kalogeromitros D, Katsarou A, Armenaka M, et al. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clinical & Experimental Allergy. 1995;25:461-466. https://doi.org/10.1111/j.1365-2222.1995.tb01078.x
Maintz L, Novak N. Histamine and Histamine Intolerance. Am J Clin Nutrition
Balla Kohn J. Is there a diet for histamine intolerance? J Acad Nutri Diet 2014;24:860.
Reese I, Ballmer-Weber B, Beyer K, Fuchs T, et al. German guideline for the management of adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI). Allergo J Int. 2017;26(2):72-79. doi: 10.1007/s40629-017-0011-5. Epub 2017 Feb 27.
What About Histamine Intolerance?