How Inflammation and the Immune System Are Fundamentally Connected to Menstruation

We tend to treat the menstrual cycle so simplistically. Uterine lining grows. Egg is released. Uterine lining sheds. Replace pads/tampons/menstrual cup. Repeat every 28-ish days. 

And while true, this narrative is so simple that it misleads because it neglects the rest of us. Treating the menstrual cycle as a story about our ovaries and uterus is wrong because it is fundamental to so many parts of our health for those of us with XX chromosomes. Every cell in our body is connected to every other cell, and that is why we at Semaine believe that periods – especially if they are painful – need to be taken seriously, and our health understood holistically.  
At the heart of the entire menstrual cycle are hormonal changes that affect not just ovulation or menstruation, but your whole body, ranging from your intestinal microbiome to your immune system. The consequences are wide ranging and important, but the immune system is what we want to talk about here because it explains so much about period pain, and yet very few of us have been told about this fundamental connection in our bodies. To be honest, no doctor has ever talked to us about it, and this has been a painstaking attempt to understand human physiology based on Lauren’s and Cath’s experiences with endometriosis. 

The big questions 

  1. Why do between 50-80% of women experience moderate to significant pain on their periods(13)?  
  2. Why does asthma often get worse when you start period(46)?  
  3. Why does IBS (Irritable Bowel Syndrome) get worse during periods(7)? 
  4. Why are you more likely to get an infection when you are ovulating(89)? 

All of these may come down to the role that inflammation and your immune system play during the menstrual cycle (1011).  

Immune system and menstrual cycle

What's happening during ovulation?

As your body approaches ovulation and prepares to release an egg, it is preparing for the possibility that a fertilized egg could be implanted in the uterine lining and begin to grow. This newly fertilized egg would have half your DNA ... and also be half-foreign. 

Your immune system relentlessly seeks out and destroys cells in your body that don’t belong there (think bacteria, viruses and even your own cells that have gone a little wonky and are looking cancerous). All of these are things that your body needs to destroy, but right around ovulation it has to prepare for the possibility that a WHOLE bunch of cells that don’t match up with your DNA are going to be growing inside you … and that your immune system isn’t supposed to kill them. 
So, hormonal cues during ovulation dial down your immune system so it is less likely to attack this newly fertilized egg, but this dialing down of the immune system also makes women more likely to get an infection during and after ovulation(8912). Once you are past that fertile window, the immune system comes back strong as your body switches into menstruation and period mode. This switch helps break up and clear out the uterine lining (and could reduce your risk of getting sick), but can also exacerbate inflammation and certain immune diseases(10).  

What happens the week of your period?

The more inflammation you have in your body as your immune system comes back and your period starts, the worse PMS you’ll probably have (1314). And although this seems resoundingly obvious because if your body is inflamed of course your PMS is going to be worse, the research about inflammation and more acute PMS was only done a few years ago. This could have important health implications because inflammation is a significant risk factor for many diseases including heart disease(15), Alzheimer’s(16) and type 2 diabetes(17). 

Inflammation and endometriosis

Women with endometriosis have even more altered immune function(1819). Although endometriosis is often talked about from an estrogen perspective, chronic inflammation and significant alterations to the immune system are fundamental to the disease and to its progression(2023).  

Scientific studies

There’s a lot more to talk about regarding studies on how reducing inflammation can affect period pain, and how this research forms the scientific basis for how we designed Semaine. So stay tuned for more juicy science info coming your way in future posts! 

  1. S.Iacovides, I. Avidon, F. C. Baker, What we know about primary dysmenorrhea today: a critical review. Hum. Reprod. Update21, 762–778 (2015). 
  2. H. Ju, M. Jones, G. Mishra, The prevalence and risk factors of dysmenorrhea.Epidemiol. Rev. 36, 104–113 (2014). 
  3. G. Grandiet al., Prevalence of menstrual pain in young women: what is dysmenorrhea? J. Pain Res. 5, 169–174 (2012). 
  4. E. M.Skobeloff et al., The effect of the menstrual cycle on asthma presentations in the emergency department. Arch. Intern. Med. 156, 1837–1840 (1996). 
  5. A. Vrieze, D. S. Postma, H. A. m.Kerstjens, Perimenstrual asthma: a syndrome without known cause or cure. J. Allergy Clin. Immunol. 112, 271–282 (2003). 
  6. A.Graziottin, A. Serafini, Perimenstrual asthma: from pathophysiology to treatment strategies. Multidiscip. Respir. Med. 11, 30 (2016). 
  7. W. E. Whiteheadet al., Evidence for exacerbation of irritable bowel syndrome during menses. Gastroenterology98, 1485–1489 (1990). 
  8. C. R. Wira, J. V. Fahey, A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle.AIDS22, 1909–1917 (2008). 
  9. W. H. Kutteh, S. J. Prince, K. R. Hammond, C. C. Kutteh, J.Mestecky, Variations in immunoglobulins and IgA subclasses of human uterine cervical secretions around the time of ovulation. Clin. Exp. Immunol. 104, 538–542 (1996). 
  10. A.Alvergne, V. Högqvist Tabor, Is Female Health Cyclical? Evolutionary Perspectives on Menstruation. Trends Ecol. Evol. 33, 399–414 (2018). 
  11. J. Jarrell, The significance and evolution of menstruation.Best Pract. Res. Clin. Obstet. Gynaecol. 50, 18–26 (2018). 
  12. M.Relloso et al., Estradiol impairs the Th17 immune response against Candida albicans. J. Leukoc. Biol. 91, 159–165 (2012). 
  13. E. R. Bertone-Johnsonet al., Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women. Hum. Reprod. 29, 1987–1994 (2014). 
  14. E. B. Gold, C. Wells, M. O. Rasor, The Association of Inflammation with Premenstrual Symptoms.J. Womens. Health 25, 865–874 (2016). 
  15. P. M.Ridker, N. Rifai, N. R. Cook, G. Bradwin, J. E. Buring, Non–HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women. JAMA294, 326–333 (2005). 
  16. Q. Taoet al., Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers. JAMA Netw Open1, e183597 (2018). 
  17. B. B. Duncanet al., Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes52, 1799–1805 (2003). 
  18. L. G. C. Riccio, E. C.Baracat, C. Chapron, F. Batteux, M. S. Abrão, The role of the B lymphocytes in endometriosis: A systematic review. J. Reprod. Immunol. 123, 29–34 (2017). 
  19. B. G. Patelet al., Pathogenesis of endometriosis: Interaction between Endocrine and inflammatory pathways. Best Pract. Res. Clin. Obstet. Gynaecol. 50, 50–60 (2018). 
  20. J.-C.Lousse et al., Peritoneal endometriosis is an inflammatory disease. Front. Biosci. 4, 23–40 (2012). 
  21. Y. Tanakaet al., Exacerbation of Endometriosis Due To Regulatory T-Cell Dysfunction. J. Clin. Endocrinol. Metab. 102, 3206–3217 (2017). 
  22. M.Králíčková, V. Vetvicka, Immunological aspects of endometriosis: a review. Ann Transl Med3, 153 (2015). 
  23. L. K. Symonset al., The Immunopathophysiology of Endometriosis. Trends Mol. Med. 24, 748–762 (2018). 


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