How Depression Could Be Driving Menstrual Pain

For millions of women, the link between mental health and physical pain remains a challenge, yet the biological connection between these conditions has been unclear. Researchers from Xi'an Jiaotong-Liverpool University have found evidence suggesting that depression may play a causal role in menstrual pain.

Published in Briefings in Bioinformatics, these findings could lead to more personalized approaches to managing mental and reproductive health.

Depression is more common in women than men

Depression is one of the most common mental health conditions, disproportionately affecting women. Studies report that 21.3% of women will face the condition at one point in their life, compared to 12.7% of men. Differences between sexes are most pronounced during reproductive years, including premenstrual, pregnancy and perimenopausal periods. Previous research has suggested this variation may be due to differences in sensitivity to neurotransmitters and hormones.

Menstrual pain – also termed dysmenorrhea – impacts between 50-90% of menstruating individuals. Women with depression often report more severe physical symptoms, such as sleep disturbances and fatigue, which can make the challenges of menstrual pain even worse. Untreated, the dual burden can result in diminished productivity, strained relationships and increased healthcare costs.

Previous studies have highlighted a connection between menstrual pain and increased rates of depression. Despite this, the precise mechanisms linking mental and reproductive health are still poorly understood.

Depression may play a causal role in dysmenorrhea

Shuhe Liu, lead author and doctoral candidate at Xi'an Jiaotong-Liverpool University, and the team used Mendelian randomization (MR) to explore whether a causal relationship existed between depression and dysmenorrhea.  Through genome-wide association studies, they analyzed genetic variants associated with these conditions and identified specific genes potentially linking depression to menstrual pain. They studied ~600,000 cases from European populations and 8,000 from East Asian populations.

The team also incorporated expression quantitative trait locus data to understand how genetic variations affect gene expression in relevant tissues. Protein-protein interaction networks and colocalization analysis were used to pinpoint shared genetic pathways and causal variants.

They found that depression may play a causal role in dysmenorrhea, with results being strongest in European populations. The causal relationship of depression on dysmenorrhea remained significant even after adjusting for factors such as sleeplessness, anorexia, body-mass index and endometriosis.  

"Our findings provide preliminary evidence that depression may be a cause, rather than a consequence, of dysmenorrhea as we did not find evidence that period pain increased the risk of depression," said Liu.

The results align with earlier MR studies linking depression to gynecological conditions such as endometriosis and reproductive health issues.

"We found that increased sleep disturbances could exacerbate menstrual pain. Addressing sleep issues may therefore be crucial in managing both conditions. However, more research is required to understand the intricate links between these factors," said Liu.

The study also highlighted genetic links between depression and dysmenorrhea, such as a specific gene RBMS3, which may influence both conditions. Biological pathways like the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-ovarian axes were identified as important in connecting mental and reproductive health.

Developing personalized treatments

"Our results provide evidence of a link between our neurological systems and the rest of the body. By exploring and understanding these relationships better, we can make a real difference to the millions of people experiencing period pain and mental health issues," said Lui.

The connection between depression and menstrual pain suggests that addressing mental health, particularly associated issues like sleeplessness, could be an effective approach to managing menstrual pain. Targeting both mental and reproductive health simultaneously may lead to more effective treatment plans.

The identification of genetic and biological pathways linking depression and dysmenorrhea may open new possibilities for personalized medicine. Tailored treatments that address these shared mechanisms could provide innovative solutions for managing the interconnected conditions.

"Mental disorders are often not considered when treating conditions such as period pain. Our findings emphasize the importance of mental health screening for people who suffer from severe menstrual pain. We hope this can lead to more personalized treatment options, improved healthcare and reduce the stigma surrounding the conditions,” Lui added.

Reference: Liu S, Wei Z, Carr DF, Moraros J. Deciphering the genetic interplay between depression and dysmenorrhea: a Mendelian randomization study. Brief Bioinform. 2024. doi: 10.1093/bib/bbae589

This article is a rework of a press release issued by Xi'an Jiaotong-Liverpool University. Material has been edited for length and content.