The following article on “Inflammation, Insulin Resistance and PCOS” by Dr. Sari Cohen was originally published in the PCOSA Newsletter “PCOSA Today”.
Scientists are investigating the role of inflammation in the pathogenesis of many conditions, including PCOS, diabetes, and heart disease. The question of whether or not inflammation is the underlying cause of PCOS remains unanswered. Also unclear is which aspect of PCOS specifically contributes to the increased risk of heart disease and type 2 diabetes: inflammation, insulin resistance, or other metabolic and hormonal disturbances? The research to date shows that insulin resistance, inflammation and the hormonal changes of PCOS are certainly related – but which came first remains a mystery.
PCOS has long been associated with insulin resistance, with many in the medical community believing that insulin resistance is the underlying cause of PCOS. Some evidence points to inflammation as causing insulin resistance. Researchers at University of California San Diego assert that inflammation induced by immune cells called macrophages leads to insulin resistance and type 2 diabetes. Their research on mice indicates that in the absence of inflammation, obesity alone does not cause insulin resistance. This means that, according to this study, some inflammatory mediators are necessary for the development of insulin resistance.
If this is true, one may extrapolate the data to indicate that women with PCOS do not develop insulin resistance unless inflammation is also involved. For this truly to be meaningful, we would have to prove that all women with PCOS exhibit signs of inflammation. This is easier said than done!
Research published in 2005 examining insulin resistance and inflammatory markers in obese and non-obese women with PCOS showed that all women with PCOS had elevated levels of inflammatory markers.
On the other hand, a study published in the European Journal of Endocrinology in 2004 concluded that PCOS was not necessarily correlated with inflammation after comparing levels of inflammatory markers CRP and IL-6 in women with PCOS to a control group. The authors write, “BMI was…the parameter most strongly related to IL-6 and CRP in PCOS… In PCOS, the type 2 diabetes risk may…be confined to those with obesity and/or metabolic alterations rather than affecting all women suffering from the syndrome.” In other words, lean women with PCOS may not be as likely to exhibit elevated inflammatory markers as their overweight counterparts with PCOS.
A similar trend was also noted in a 2003 study examining the effects of metformin therapy in lowering CRP levels in women with PCOS, where the researchers suggested that elevated CRP was related to obesity rather than PCOS itself.
Another article published in September 2007 in Gynecological Endocrinology concluded that obesity, rather than inflammatory markers, represented the greater factor in predicting whether or not women with PCOS would develop heart disease and/or type 2 diabetes.
Perhaps the contradictory results may be due to the fact that the community of women with PCOS is very diverse, not only ethnically but also phenotypically (that is, the physical manifestation of the disease). Furthermore, these studies have a relatively small number of participants, usually less than 100 people. Both of these factors may confound the attempt to simplify the issues of finding the one underlying cause of PCOS and even of the historical difficulty in establishing criteria for the definitive diagnosis of PCOS.
In conclusion, we clearly need more research with larger numbers of participants to determine the interrelationship between inflammation and insulin resistance in PCOS, and how these factors relate to hormonal imbalance and cardiovascular risk factors. This issue is important because it could dictate changes in treatment strategies for women with PCOS. Furthermore, more attention needs to be paid to the great ethnic diversity in this population with a future focus on examining trends among specific ethnic groups.
(1) As reported in ScienceDaily (Nov 7, 2007)
(2) Yilmaz M. et al. Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome. Gynecol Endocrinol. 2005 May;20(5):258-63. PMID: 16019370
(3) Mohlig M. et al. The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol. 2004 Apr;150(4):525-32. PMID: 15080783
(4) Morin-Papunen L. et al. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Oct;88(10):4649-54. PMID: 14557435
(5) Guzelmeric K. et al. Chronic inflammation and elevated homocysteine levels are associated with increased body mass index in women with polycystic ovary syndrome. Gynecol Endocrinol. 2007 Sep;23(9):505-10. PMID 17852421