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Atorvastatin impaired glucose tolerance in women with PCOS
Atorvastatin therapy appears to impair glucose tolerance in women with polycystic ovary syndrome and should only be given after risk assessment for cardiovascular disease, according to data from a Finnish study.
Researchers sought to explore the effect of atorvastatin (Lipitor, Pfizer) therapy on hormonal and metabolic parameters in women with PCOS by conducting a randomized, double blind, placebo-controlled 6-month follow-up study at Oulu University Hospital in Finland.
“Atorvastatin therapy seems to impair glucose tolerance in women with PCOS. This should be taken into account when considering statin therapy in women with PCOS, because these women present with an increased risk of developing type 2 diabetes. Hence, statin therapy should be initiated with consideration and be based on generally accepted criteria and individual risk assessment of CVD, and not only because of a diagnosis of PCOS,” researchers wrote.
The women with PCOS (based on Rotterdam criteria) were assigned atorvastatin 20 mg per day (n=15) or placebo (n=13). Their mean age, BMI, waist-to-hip ratio, systolic and diastolic blood pressure, and plasma levels of creatinine remained unchanged after 3 and 6 months of treatment, according to data. Levels of plasma creatinine and alanine transaminase increased slightly but significantly in the atorvastatin group during the treatment, researchers wrote.
Alanine transaminase levels differed significantly between groups at baseline and at 3 and 6 months, according to data.
In the atorvastatin group, three patients (20%) were overweight (BMI: 25 to 30) and seven patients (47%) were obese (BMI: 30).
In the placebo group, three patients were overweight (23%) and three patients were obese (23%). At baseline screening, one patient in the atorvastatin group and one patient in the placebo group were diagnosed as having IGT.
Fasting levels (14.7 vs. 7, P=.002) and area under the curve of insulin (5.5 vs. 5, P=.007) increased significantly and insulin sensitivity indexes decreased during 6 months of atorvastatin therapy (0.51 vs. 0.93, P=.006; Matsuda index 3.65 vs. 9.19, P=.002), according to researchers.
Serum dehydroepiandrosterone sulfate levels decreased in the atorvastatin group, whereas no
differences were observed in serum testosterone levels, researchers wrote. Levels of C-reactive protein, total and LDL cholesterol, and triglycerides decreased significantly during statin therapy.
Disclosure: Atorvastatin and placebo were provided by Pfizer Inc. The researchers report no relevant financial disclosures.
Perspective
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Short-term studies have reported a beneficial effect of statins to reduce circulating testosterone in women with PCOS. This study by Puurunen and colleagues is a longer-term (6 months) placebo-controlled trial of atorvastatin in PCOS. Serum testosterone did not change in the women treated with atorvastatin, but the more pertinent finding was a decrease in insulin sensitivity as determined by several different methodologies. This finding is consistent with reports that statin use in the general population may be associated with impairment of glucose tolerance and development of diabetes. There has always been a concern about treating premenopausal women with PCOS with statins because of the risk of teratogenicity, but the present study raises the additional concern that statins may enhance the risk of developing diabetes in women with PCOS – a group already at high risk for diabetes at baseline. The effect of statins in PCOS remains a research topic, but the possible utility of statins for the treatment of androgen excess in PCOS seems questionable.