Abstract / Summary
Background: Dysmenorrhoea and endometriosis-associated pelvic pain are among the most common causes of pain in women of reproductive age. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies are the standard of care, but both have limits on tolerability, contraindications and compatibility with fertility goals. Palmitoylethanolamide (PEA) is an endogenous fatty-acid amide that modulates inflammation and pain. It acts mainly through peroxisome proliferator-activated receptor-α (PPAR-α) and by down-regulating mast cells and glia. Methods: This narrative review summarises the pharmacology of PEA and the clinical studies of oral PEA, alone or in combination, in primary dysmenorrhoea and endometriosis-associated pelvic pain. It also draws on recent meta-analyses of PEA in chronic pain. Results: In a randomised, double-blind, placebo-controlled trial in 61 women after laparoscopy for endometriosis, micronised PEA with trans-polydatin (400 mg/40 mg twice daily for 3 months) reduced pelvic pain more than placebo. Open-label studies report reductions in pelvic pain, dysmenorrhoea and dyspareunia, with improved quality of life. A 2017 meta-analysis of four studies, all of low quality, found clinically relevant improvement in chronic pelvic pain and dysmenorrhoea. In primary dysmenorrhoea, a randomised study of 220 young women and a 2025 double-blind crossover trial of single-dose PEA (300 mg) both reported less menstrual pain than placebo. No serious adverse events were attributed to PEA in any study reviewed. Conclusions: PEA is a biologically plausible, well-tolerated option for women with dysmenorrhoea and endometriosis-associated pain, particularly when NSAIDs or hormonal therapy are unsuitable. The evidence is still limited by small samples, open-label designs and the frequent use of PEA in combination products. Adequately powered, double-blind trials of PEA alone are needed.