For a condition as widespread as Premenstrual Symptoms (PMSx) and as frequently debilitating, the lack of research into causes is astonishing. A new paper in the Journal of Women's Health reports the largest and most diverse investigation of the possible relationship between PMSx and inflammation. In the process, the authors have identified a protein that could be targeted for future medications.
“About 80 percent of women may experience PMSx,” the paper reports. In developed nations half of women can seek medical care for symptoms including “irritability, depression, fatigue, water retention, weight gain, breast tenderness, headaches, abdominal cramps, and mood swings.”
Nevertheless, little is known about the causes, something only a cynic would attribute to the historical domination of medical research by people who don't menstruate. However, High-Sensitivity C-reactive protein (hs-CRP), has previously been found to be associated with some of the factors linked to increased PMSx risk. Hs-CRP is an indicator of inflammation also associated with cardiovascular disease. Small sample studies, in the paper's words, have “found suggestive, but not always significant, differences in inflammation between women reporting and women not reporting emotional or physical PMSx.”
Combining this with the relief many PMSx sufferers experience when using anti-inflammatory agents, inspired Dr Ellen Gold of the University of California, Davis to investigate further. She recruited 3,302 racially diverse American women aged 42 to 52 who were not using hormone therapy or oral contraceptives. The women answered a survey on the timing and extent of eight common PMSx symptoms and were tested for hs-CRP.
Women with hs-CRP values greater than 3 milligrams per liter were significantly more likely to suffer from six of the eight symptoms, with breast pain and headaches the exceptions. The relationship remained after checking for confounding factors. Obesity, smoking, and depression were also associated with most of the symptoms.
The authors caution that establishing causality “requires future investigation using longitudinal data to establish the temporal sequence.” It is, for example, possible that the inflammation is a response to treatments for PMSx. Nevertheless, they argue the findings “have potential clinical implications for the treatment of these symptoms, and possibly prevention” by avoiding factors known to trigger inflammation.
Promising as all this sounds, hs-CRP only made women modestly more likely to experience these symptoms. Low levels were far from a guarantee of relief, so even highly effective anti-inflammatory intervention is unlikely to provide a total cure. Hispanic women without inflammation were more likely to experience cramps, for example, than women with east Asian backgrounds and high hs-CRP levels.
An accompanying editorial by Elizabeth Bertone-Johnson of the University of Massachusetts commented: “Establishing PMS as an inflammatory condition suggests that PMS may be a useful sentinel of future chronic disease risk.”