Can Antihistamines Help Women With PMDD?

Women online are sharing an unusual over-the-counter treatment for premenstrual dysphoric disorder (PMDD) symptom relief: doubling up on antihistamines.

In one video, a woman said that after taking fexofenadine (Allegra) and famotidine (Pepcid AC) she “felt a wave of joy come over my brain and body, like somebody pressed a button” and that she felt relief within 45 minutes.

Sidra Yunas, MD, an ob/gyn at UTHealth Houston, told MedPage Today that with PMDD, a more extreme version of premenstrual syndrome, symptoms generally occur the week before someone’s menstrual cycle. Estrogen and progesterone levels change throughout the month, which is what drives the different phases of the menstrual cycle.

But what do antihistamines have to do with fluctuating estrogen and progesterone levels?

Zachary Rubin, MD, a pediatric allergist who practices near Chicago, has reacted on social media to a few videos of women praising the antihistamine hack. He explained that “estrogen and progesterone interact with cells of your immune system, like mast cells, which contain histamine.” Histamine is the chemical that causes many allergy symptoms, but it also does other things, like regulating mood, hunger, and sleep.

“So when you have these fluctuations in estrogen and progesterone, it can affect mast cell activation and the number of histamine receptors where this chemical can bind to and create different actions on the body,” he said.

Yunas explained that estrogen upregulates mast cells, making them more activated, while progesterone stabilizes them. During the luteal phase, which follows ovulation and ends before menstrual bleeding, estrogen is higher and progesterone drops quickly, meaning there is more histamine release at the point in the cycle when PMDD symptoms tend to be worst. The idea behind taking antihistamines for PMDD is to down-regulate histamine release.

“In theory what it’s doing is it’s decreasing histamine in our body, and in turn, helping with the mood changes, irritability, sleep disturbances, hunger, and inflammation,” Yunas said.

Rubin noted that the two drugs women are taking to mitigate PMDD symptoms are in different antihistamine classes. Fexofenadine works on the H1 receptor while famotidine, an antacid, works on the H2 receptor.

Still, the standard of care for PMDD “does not involve antihistamines, because there’s no clinical trials on this to really understand whether this works,” he said.

Yunas said that physiologically, the double antihistamine combination makes sense, but until there are clinical trials proving that it works to treat PMDD beyond the cellular level, other evidence-backed treatments are better.

Selective serotonin reuptake inhibitors and hormonal birth control are better studied treatments for PMDD. Lifestyle interventions that increase serotonin, like exercise, are known to help as well. Yunas said that if anything, taking the two antihistamines could be a potential adjunct therapy to these other options, but not as primary therapy until it’s better studied.

Yunas also noted that there’s probably a level of placebo effect at play and that any benefits wouldn’t take effect within an hour like some people claim.

“PMDD is truly a severe medical condition” requiring medical treatment, Yunas emphasized. While taking antihistamines is likely not harmful, unless a patient was taking a contraindicated medication, she said, it might not be the full extent of care that a patient suffering from PMDD can get and deserves to have.