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SUZHOU, China — Up to 90% of girls and women who menstruate experience pain during their periods. For some, that pain is severe and linked with symptoms of depression, which are often thought to be a result of the intense throbbing or cramps.
But a new study published Wednesday in the journal Briefings in Bioinformatics suggests it may be depression causing period pain, due to specific genes the authors identified — while other researchers said the interplay of internal mechanisms is more complicated than that.
"Depression and menstrual pain significantly impact women's lives across the world, yet their connection remains poorly understood," lead author Dr. John Moraros, dean and professor at the School of Science at Xi'an Jiaotong-Liverpool University in China, said via email. "Our collective goal is to critically investigate these issues and improve care for women by uncovering these complex connections and finding better ways to address them."
Menstrual pain is known as dysmenorrhea, which occurs in the pelvis or abdomen for typically up to three days once the bleeding starts. Previous studies have shown a correlation between dysmenorrhea and depression but didn't establish a causal relationship at the genetic level, Moraros said.
"We used a clever approach called Mendelian randomization," he said. "This method works like nature's experiment. It uses genetic data … to see if having certain genes linked to depression also makes people more likely to have menstrual pain. This helps us understand cause-and-effect without the need to test it directly on people."
The authors collected the genetic data of around 600,000 people from European populations and 8,000 from East Asian populations from various sources, including the UK Biobank study, the Psychiatric Genomics Consortium and FinnGen, a large-scale research project in genomics and personalized medicine.
"Next, we used bioinformatics," Moraros said. "It helps us find patterns in the genes and biological pathways that connect depression and menstrual pain."
The study contends it has demonstrated a "significant" causal relationship between depression and dysmenorrhea, with the mood disorder increasing the odds of menstrual pain by 1.51 times, or 51%. The authors found several genetic pathways and proteins through which depression may affect reproductive function.
The research team also found that sleeplessness, experienced by some people with depression, may worsen the link between depression and dysmenorrhea. No evidence was found to support a causal effect of dysmenorrhea on depression, however, the authors said.
The findings help expand the important, and often overlooked, discussion around mental health and period pain.
"I'm excited about some of the potential for some of these larger database-style studies, especially as more genetic testing is advancing," said Dr. Anne-Marie Amies Oelschlager, professor of obstetrics and gynecology at the University of Washington School of Medicine. She wasn't involved in the new research.
But there are also concerns about some of the study's broader assertions, according to Amies Oelschlager and other experts.
"Where I think the paper's falling short is that because there's a strong genetic connection, you attributed that as a causal relationship, and I think it's still a stretch," said Dr. Claudio Soares, president of the Menopause Society and professor in the department of psychiatry at Queen's University School of Medicine in Kingston, Ontario. Soares also wasn't involved in the study.
Below, experts elaborate on newfound and known associations between period pain and depression, why a genetic cause can't be inferred from a genetic connection, and ways you can manage depressive symptoms and painful periods.
Two-way street between mood and painful periods
Many people who have depression or other mood disorders experience pain more acutely, said Amies Oelschlager, also chairwoman of the Committee for Clinical Consensus–Gynecology at the American College of Obstetricians and Gynecologists.
That increased intensity is due to how the brain interprets and experiences pain signals, and to depression limiting one's ability to cope with pain, she added. But Amies Oelschlager said she also wouldn't tell someone with dysmenorrhea "you must have this gene," since for many, some level of pain during menstruation is normal.
Primary dysmenorrhea is caused by highly active prostaglandins, the chemicals that cause the uterus to contract during the menstrual cycle, Amies Oelschlager said. "That's why ibuprofen is so effective, because it's a prostaglandin inhibitor."
The disorder is also associated with early menopause, Soares said.
Additionally, the Mendelian randomization method assumes there are no environmental factors that could influence someone's depression status, period pain or genetics — which contradicts the fact that the relationship between those things can be multifactorial and different for everyone, experts said.
There are probably also underlying mechanisms making people more vulnerable to having both depression and dysmenorrhea, Soares said.
Since the study doesn't have more personal data at an individual level, it's unclear whether differences in individuals' severity and treatment of depression would also affect the results, Amies Oelschlager said.
On the other hand, experts noted that the opposite relationship — period pain or reproductive shifts preceding depression — has occurred in both human and animal research and in clinical practice.
"We know that's true in patients with some chronic pelvic pain conditions, something we call central sensitization, where the brain becomes more sensitive to even normal stimuli and starts to feel them as painful," said Dr. Hugh Taylor, the Anita O'Keeffe Young Professor and chairman of the department of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine. Taylor wasn't involved in the study.
In animal models, endometriosis, a secondary cause of dysmenorrhea, led to depression. Endometriosis is a chronic disease in which tissues similar to the uterine lining grow outside, rather than inside, the uterus, causing pain and fertility issues.
And women with dysmenorrhea may be more likely to experience postpartum depression, Taylor added.
Experts have also known for years that having your first period at an early age increases your risk for depression, Soares said.
