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Women with PCOS benefited from statin therapy
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Data recently published in The Journal of Clinical Endocrinology & Metabolism demonstrated that 12 weeks of statin therapy reduced inflammatory markers, insulin resistance and hyperandrogenemia in women with polycystic ovary syndrome.
Researchers from the University of Hull in the United Kingdom conducted a randomized, double-blind, placebo-controlled trial to determine the effects of statin therapy in women with PCOS.
The study included 40 patients with PCOS and biochemical hyperandrogenemia. Patients were a mean age of 27.7 years. Patients were randomly assigned to atorvastatin 20 mg daily or placebo. After four weeks, two patients from the placebo group and one from the atorvastatin group dropped out due to noncompliance.
After 12 weeks, the researchers reported an absolute reduction in total cholesterol (–26.4% change), LDL cholesterol (–36.6%), triglycerides (–20.9%), free androgen index (–32.7%) and total testosterone (–24.6%) among patients in the atorvastatin group. Sex hormone–binding globulin increased by 13.7% in the atorvastatin group. According to the researchers, patients assigned to placebo did not experience changes in any of these parameters.
Patients in the atorvastatin group had lower serum insulin levels and homeostasis model of insulin resistance (HOMA-IR) compared with the placebo group who experienced increases in both of these parameters.
The researchers reported a link between the reduction of HOMA-IR and improvement in free androgen index (P=.04) in patients assigned to atorvastatin. The reduction of HOMA-IR was also associated with a reduction in triglycerides (P<.01). According to the researchers, there was no linear relationship between the reduction in total cholesterol and improved free androgen index (P=.95), testosterone (P=.69) or sex hormone–binding globulin (P=.22).
J Clin Endocrinol Metab. 2008;doi:10.1210/jc.2008-1750.
This investigation has been long overdue. The effects of statins on parameters of insulin resistance and systemic inflammation are of strong interest from several perspectives. From a clinical point of view it emphasizes that women with PCOS need to have their lipoprotein lipids screened and they need to be checked for carbohydrate abnormalities. We now know that abnormal lipoprotein lipid particle tracking in women is associated with atherogenic progression. When contraception is assured, these potent agents are first-line therapy after diet and exercise to first target LDL cholesterol to normal levels (LDL=100 mg/dL). Often statins are not enough and non-HDL is a secondary target. This should be maintained below 130 mg/dL unless a PCOS patient is diabetic or has more than 2 cardiovascular disease risk factors (see American Heart Association, National Cholesterol Education Program national guidelines) when targets are even more severe (70 mg/dL for LDL and 100 mg/dL for non-HDL cholesterol).
From a mechanistic point of view this study highlights the potential interface between systemic inflammation and insulin resistance. While the anti-inflammatory pleiotropic effects of statins are assumed to be in play, the authors here are measuring associated correlated changes presumably because of the anti-inflammatory properties of this particular HMG-CoA reductase inhibitor. Of interest is how sex hormone-binding globulin increased and free androgen index dropped when this agent was used.
The researchers rightfully warn about the avoidance of pregnancy because of strong warning about teratogenicity. Of interest are further studies looking at the effects of alternative agents used to keep LDL cholesterol and non-HDL cholesterol and triglycerides to goal. Further research elucidating metabolic effects of many types of statins and combination agents is likewise of strong interest.
– Robert Wild, MD, PhD, MPH
Professor of Reproductive Endocrinology,
Oklahoma University Health Sciences Center, Oklahoma City