Understanding the Molecules Behind Period Pain—and What Might Help

Period pain (also known as dysmenorrhea) affects more than 4 in 10 women and is one of the leading reasons young people miss school or work. Despite how common it is, scientists still don’t fully understand what causes this pain—or how to treat it most effectively.

To explore this further, we reviewed 15 scientific studies that analyzed the substances (biomolecules) found in menstrual fluid. We focused on whether these molecules are linked to pain, and whether non-hormonal treatments like ibuprofen (which blocks inflammation) change their levels.

Our review confirmed that many people with period pain have higher levels of prostaglandins—molecules that cause the uterus to contract, leading to cramping and pain. Anti-inflammatory drugs like ibuprofen can reduce prostaglandin levels, but most studies used multiple doses over several days. It's still unclear how well a single dose works on these molecules.This review is available at the journal of Molecular Pain- see https://doi.org/10.1177/17448069251360092

Interestingly, a few small studies identified other molecules that may also play a role. One of these, PAF (platelet-activating factor), was found at higher levels in people with dysmenorrhea. In animal studies, PAF has been shown to affect uterine activity and pain. Drugs that block PAF—such as rupatadine, BN52021, and Lexipafant—have been tested safely in humans for other conditions and may be worth exploring in menstrual pain research.

Another molecule, 12-HETE, may also contribute to pain. This suggests that targeting multiple inflammatory pathways—such as those controlled by COX-2, LOX, and cytochrome-P450 enzymes—could be more effective than standard treatments. Drugs like Zileuton (a 5-LOX inhibitor) and GSK2256294A (a soluble epoxide hydrolase inhibitor) are promising candidates for future study.

While these findings are preliminary and based on small studies, they point to the possibility of new, more targeted treatments for menstrual pain. Larger, better-designed clinical trials are needed to test whether these alternative pathways and medications can offer relief to the many people living with dysmenorrhea.