The genetics of primary dysmenorrhea: a systematic review

Abstract Dysmenorrhea is the most common gynaecological condition in women of reproductive age. Approximately 90% of cases are primary dysmenorrhea (PDM) which is not associated with underlying pathology. Dysmenorrhea can have a substantial impact on quality of life, yet current therapies do not provide adequate relief for everyone. Family history is a known risk factor which suggests genetic involvement. We therefore aimed to synthesize the literature describing the genetics of PDM. Three databases (Medline, Embase, Web of Science) were searched for studies published up to November 2025. Key search terms included “dysmenorrhea”, “polymorphism” and “SNP”. Articles were screened independently by two researchers and data were extracted and presented in narrative format. Quality assessment was conducted using the Newcastle–Ottawa Scale and STREGA guidelines. Fifteen articles were included in the review (N=7 case–control; N=4 cross-sectional; N=4 genome-wide association studies [GWAS]). Candidate gene studies identified seven polymorphisms and two combined genotypes that were associated with PDM. One significant positive association was replicated in two studies (ESR1 PvuII). GWAS highlighted loci near the NGF, ZMIZ1, IL1A and IL1B genes. The NGF and IL1 loci support what is known about the involvement of inflammatory pathways in PDM pathogenesis. However, they are also known endometriosis loci. Current literature is limited by a lack of adequate secondary dysmenorrhea case exclusion, limited ethnic populations and low quality. Further research in multiple ancestries is essential to increase generalisability, while thorough diagnostic protocols will reduce misclassification, improve understanding of PDM pathogenesis and thus help inform new treatment development. Lay summary Period pain is extremely common in menstruating women and has a major impact on their lives, yet we still don’t have a full understanding of its biological causes or how to treat all women effectively. Research shows that period pain can run in families, therefore we conducted this review to highlight which genes appear to be related to period pain (specifically period pain that isn’t caused by an existing condition like endometriosis or fibroids). After searching three academic databases, we found 15 studies that met our criteria. Three genes were highlighted across two or more studies; these genes are known to be involved in pain processing and how the body deals with immune responses and oestrogen (a female hormone). From this review, we know that we need more research on this topic as there are still likely to be more genes involved in period pain and these might vary in different ethnic populations.