Metformin Reduces Serum C-Reactive Protein Levels in Women with Polycystic Ovary Syndrome

Abstract

Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) </= 25 kg/m(2)] and 32 obese women (BMI >/==" BORDER="0"> 27 kg/m(2)) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 micro g)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 +/- 0.53 (SE) vs. 1.31 +/- 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 +/- 0.68 mg/liter to 4.58 +/- 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.

Effects of metformin and ethinyl estradiol–cyproterone acetate on lipid levels in obese and non-obese women with polycystic ovary syndrome

“…In the combined group of non-obese and obese women the mean BMI decreased slightly at 3 months and significantly at 6 months, and WHR decreased significantly during metformin treatment, as published previously (21). Similarly, serum levels of HDL cholesterol increased and the cholesterol:HDL ratio decreased significantly at 3 and 6 months of metformin treatment, and serum triglyceride levels tended to decrease (P ¼ 0.09, Table 2).…”

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

“…The importance of insulin sensitivity rather than body weight is supported by observations of CRP changes in patients receiving various treatments during which body weight was not affected. Metformin for women with polycystic ovary syndrome lowered CRP concentrations without a change in body weight, 43 the result of which also occurred with lipid-lowering statin regimens. 30,44 In contrast, oestrogen supplementation for postmenopausal women increased CRP but did not affect body weight.…”

Is there an estrogenic component in the metabolic syndrome?

“…Overall it can be noted that CRP levels are higher in women than in men and that they are positively correlated with the BMI (Khera, et al, 2005). Additionally an improvement of elevated CRP levels can be achieved by insulin sensitizers in overweight patients with type II diabetes (Chu, et al, 2002) as well as in women with polycystic ovary syndrome (Morin-Papunen, et al, 2003). Both diseases comprise an insulin resistance syndrome which can be treated with insulin sensitizers such as thiazolidinediones.…”