The genetics of primary dysmenorrhoea: a systematic review

Dysmenorrhoea is the most common gynaecological condition in women of reproductive age. Approximately 90% of cases are primary dysmenorrhoea (PDM), which is not associated with an underlying pathology. Dysmenorrhoea can have a substantial impact on quality of life, yet current therapies do not provide adequate relief to everyone. Family history (FHx) is a known risk factor that suggests genetic involvement. We therefore aimed to synthesise the literature describing the genetics of PDM. Three databases (MEDLINE, Embase and 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 a 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; and n = 4 genome-wide association studies (GWASs)). 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). GWASs 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. The current literature is limited by a lack of adequate secondary dysmenorrhoea 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.

Period pain is extremely common in menstruating women and has a major impact on their lives, yet we still do not 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 is not caused by an existing condition, such as 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.