Histamine is a molecule that your immune system creates in response to allergens. Some researchers have studied the relationship between histamine and estrogen, but most of these are observational studies from the 1960s and 1970s (e.g., Ferrando 1968, Jonassen 1976, Shelesnyak 1959).

Antihistamines are medications that block the action of histamine to reduce allergy symptoms. It is certainly possible that histamine could play a role in PMDD, at least for some people. However, using antihistamines to treat PMDD symptoms has not been studied enough to know whether this is an effective treatment or the potential mechanisms.

First-generation antihistamines (such as hydroxyzine/Vistaril) do have sedative effects, which can have anti-anxiety or sleep benefits. This mechanism may explain why some individuals anecdotally report that antihistamines help their PMDD symptoms if they experience sleep problems or anxiety premenstrually.

Antihistamines are typically well tolerated by many and have limited risk, hence being available without a prescription. If they are an option you are considering, always consult a care provider and/or pharmacist - especially if combined with other meds- and be mindful of any sedative effects.

Summary: Antihistamines have not been tested or approved for PMDD, and research (such as clinical trials) would need to be done before we could state if there is a known benefit/whether it beats a placebo.

We have been hearing mixed patient anecdotes and have communicated these patient anecdotes to scientists working in this area.

Added June 2023