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\n Animation: The Cut; Photo\/Video: Getty\n <\/p>\n
Before perimenopause<\/a>, Angela hiked over 100 miles a month. \u201cI was incredibly active,\u201d she told me. \u201cI moved to the mountains so I could hike,\u201d she tells me. Then: \u201cMan, oh man,\u201d she says with a sigh. \u201cPerimenopause wiped me out.\u201d<\/p>\n With approval from her doctor, Angela began taking HRT, or hormone replacement therapy<\/a>, for her symptoms, but it didn\u2019t make a big enough dent. She was still fatigued and worse, almost completely uninterested in her former hobbies, hiking included. Then, a few months ago, Angela saw a social-media post from a woman who took daily antihistamines (like Allegra, Claritin, or Zyrtec) plus Pepcid AC (a common antacid) for her perimenopause symptoms. Her results, as reported, sounded miraculous: no more brain fog. No more tossing and turning all night. Even her mood vastly improved.<\/p>\n Angela, who is now 55, decided to try the regimen for herself. A former neuroscientist turned data scientist, she was better equipped than most to understand why these ordinary, over-the-counter medications might work to reduce peri- and menopausal symptoms; she knew that hormonal changes can trigger inflammation<\/a> in the body, which antihistamines can help reduce. (Allergy medications like Allegra and Zyrtec block histamine at H1 receptors<\/a>, while Pepcid AC is a histamine-2 blocker.) Angela has since shared her own experiences \u2014 and related research \u2014 on Threads<\/a>, where a number of users\u2019<\/a> posts<\/a> about taking these drugs have gone<\/a> viral<\/a> in recent weeks.<\/p>\n While the most recent online chatter<\/a> around antihistamines is predominantly connected to treating perimenopause or PMDD<\/a> symptoms (which can overlap), these medications have also found favor among people affected by a number of chronic, difficult-to-diagnose illnesses, including mast cell activation syndrome<\/a> (MCAS), long COVID<\/a>, and post-orthostatic tachycardia syndrome<\/a> (POTS).<\/p>\n Zachary Rubin, an allergist and clinical immunologist, has seen patients who take antihistamines for these purposes for years.<\/p>\n \u201cWomen will go to their doctors and say, \u2018I take Allegra and Pepcid and my PMDD symptoms go away. It\u2019s like magic,\u2019\u201d he told me over the phone from his office outside Chicago. He says he\u2019s been getting more questions about this OTC cocktail after his recent interview about it with OB\/GYN and menopause expert Mary Claire Haver on her Substack<\/a>. So far, Rubin says, these experiences are clinically unsupported. \u201cWhen you look at the literature, there are no clinical trials that actually validate and verify that information,\u201d he says \u2014\u00a0however, he notes, that does not mean it\u2019s not working for anyone, and there are plausible reasons for why it might work.<\/p>\n \u201cThere are some studies that suggest that there is dysregulation of the chemical histamine during the luteal phase of the menstrual cycle, which also often corresponds with the symptoms that women report from PMDD,\u201d Rubin says. Histamine also plays a role in<\/a> the sleep-wake cycle, mood, digestion, and pain signaling, and many of these systems are dysregulated during hormonal changes. For these reasons, he adds, it \u201cmakes sense mechanistically\u201d that these medications might provide relief for PMDD and perimenopause symptoms.<\/p>\n Lisa Mosconi, a neuroscientist and author of The Menopause Brain<\/a>, agrees. \u201cBiologically, it\u2019s plausible because ovarian-hormone fluctuations can influence immune activity and mast-cell signaling,\u201d she says. (Mast cells<\/a> are often described as the body\u2019s \u201calarm system\u201d and, when overprotective, can cause unnecessary activation, as is thought to be the case with MCAS.) This antihistamine \u201cblockade\u201d might help dampen that signaling, Mosconi says.<\/p>\n For Henry, a 30-year-old writer, these drugs have provided enormous relief. After a COVID infection became long COVID, and later POTS, most doctors he saw told him his symptoms were caused by his being overweight. \u201cFor a year I had no idea what was going on with me, but I just felt so strange and bad,\u201d he tells me. Henry, who is transmasculine, also experiences severe PMDD and decided to start taking Pepcid AC for PMS after seeing it recommended on TikTok. It seemed to alleviate his mood swings and brain fog almost instantly.<\/p>\n Henry brought his findings to his new psychiatric nurse practitioner, whom he says is more versed in chronic illness and mental health. He also asked her if he could start taking daily Allegra for allergies; she told him she recommended it, having heard Allegra in combination with Pepcid was helpful for people with long COVID and POTS. He\u2019s taken both for a year: Allegra daily and Pepcid for the ten or so days leading up to his cycle. (\u201cI don\u2019t want to be taking Pepcid every day, because I don\u2019t know what the long-term effects are,\u201d he explains.) Since starting the regimen, he says his symptoms \u2014 brain fog, malaise, reduced executive functioning \u2014 have improved enormously.<\/p>\n Sibyl, a 49-year-old consultant, has also been taking daily Zyrtec and Pepcid for a few weeks after reading about it online. For her, it\u2019s helped enormously with joint pain \u2014 a perimenopause symptom exacerbated by her lifelong hypermobility. Though she\u2019s in frequent physical therapy, and takes prescribed Celebrex for pain, she\u2019s found \u201covernight relief\u201d with these antihistamines. \u201cI took it one night, and I was shocked when I woke up the next day,\u201d she says. Her relief might have something to do with how well she slept, she says \u2014\u00a0Zyrtec can cause drowsiness, and since taking it, Sibyl says she\u2019s sleeping through the night for the first time in a long time.<\/p>\n When Sibyl brought up her results with her physical therapist and then her OB\/GYN, they were supportive. Next, she plans to consult her allergist. \u201cI\u2019m gonna get a group consensus on this, but I\u2019m still taking it because it\u2019s working,\u201d she says. For her, the medications have come with additional, and unexpected, benefits. \u201cI have tinnitus, where one of your ears rings all the time \u2014 I got it from a really bad ear infection ten years ago,\u201d she says. \u201cIt\u2019s super-weird, but this is the only thing I\u2019ve ever done that turns the volume way down.\u201d<\/p>\n Among those using antihistamines for off-label conditions, there is substantial variation in routine \u2014\u00a0which is part of the reason a clinical trial would be helpful, Rubin says. \u201cWe haven\u2019t had clinical trials to understand the proper dosage,\u201d he explains. \u201cHow effective is it? Is there a placebo effect involved or not? What is the overall safety?\u201d Rubin notes that while Pepcid AC and antihistamines like Allegra or Zyrtec are sold over the counter, and therefore considered very safe, they aren\u2019t entirely without associated risk.<\/p>\n \u201cAllegra is generally safer, but you can have weight gain and itching that can occur if you stop the medication too quickly,\u201d he adds. \u201cFor Pepcid, while it\u2019s rare to have long-term concerns, there could be issues related to absorption of nutrients like vitamin B-12, magnesium, and calcium.\u201d People with kidney disease need to be particularly careful with long-term Pepcid use, he adds, as it can exacerbate side effects<\/a>.<\/p>\n Mosconi, the neuroscientist, warns that anyone interested in adopting this regimen should consult their clinician, especially if taking them for off-label uses having to do with mood and cognition. Rubin agrees. \u201cI don\u2019t want to miss something that is underlying that could be explaining these symptoms,\u201d he says. \u201cWe don\u2019t want to leave any stones unturned.\u201d For perimenopause, says Mosconi, \u201cThere are more evidence-based options.\u201d<\/p>\n Still, she\u2019s sympathetic to patients\u2019 frustration with insufficient research and treatment options. \u201cWomen\u2019s midlife health has been chronically underfunded, and these are inexpensive generic [medicines] with little commercial incentive to sponsor large trials,\u201d she explains. \u201cAdd in the complexity of studying cyclical symptoms and heterogeneous presentations, and you get a gap where anecdotes spread faster than the science, despite the fact that this is exactly the kind of question we should be testing rigorously.\u201d<\/p>\n Rubin hopes that renewed online attention to these medications\u2019 off-label potential might result in more research but doesn\u2019t seem especially optimistic: As health care becomes more corporatized, and public trust in health-care systems declines<\/a>, people are bound to seek alternatives. \u201cMost adults will search for health information online,\u201d Rubin says. \u201cOne of the powerful tools that social media has is storytelling and people sharing their lived experiences.\u201d<\/p>\n Sibyl says she\u2019s been surprised by the intensity of the response to her post<\/a> on Threads, but it\u2019s obvious the underlying frustration is resonant. \u201cI saw someone else say<\/a> that it feels like every woman over 35 is doing a drug trial in their living room, and that\u2019s what\u2019s happening,\u201d she says. \u201c \u2018Lose weight, you\u2019re fat and anxious\u2019 is the answer to everything at a doctor\u2019s office, no matter where you go. We all get dismissed.\u201d<\/p>\n Related<\/p>\n