SAN DIEGO, California — Atorvastatin impaired insulin sensitivity in women with polycystic ovary syndrome (PCOS) and should not be prescribed unless patients also demonstrate risk factors for cardiovascular disease, according to research presented here at the American Society of Reproductive Medicine (ASRM) 68th Annual Meeting.
Some studies have suggested that statins could potentially benefit women with PCOS by decreasing serum testosterone levels and by helping to address hyperandrogenism. However, the drugs' effect on patients' glucose tolerance has been a concern.
In an effort to further investigate that relationship, researchers in Finland and the United States conducted a randomized, double-blind study in which 28 women with PCOS received either atorvastatin 20 mg/day (n = 15) or placebo (n = 13) for 6 months.
Oral glucose tolerance tests showed significant increases in fasting insulin levels in the atorvastatin group after 6 months, and there were decreases in insulin sensitivity. Measurements by intravenous (IV) glucose tolerance tests did not show changes in insulin sensitivity in either group, however.
The atorvastatin group showed decreases in serum levels of dehydroepiandrosterone sulphate, but there was no change in testosterone levels. Lipid profiles improved, and serum levels of C-reactive protein decreased significantly among those using statin therapy.
"Previous studies have indicated that statins improve hyperandrogenism; however, our results did not support these results, as serum testosterone levels did not change during statin treatment," lead author Juha S. Tapanainen, MD, of Oulu University Hospital's Department of Obstetrics and Gynecology, in Finland, told Medscape Medical News.
"On the other hand, our results are in line with some previous studies which have shown an increase in insulin resistance during statin therapy, and therefore, we would recommend statin therapy only when women with PCOS have also other risk factors of cardiovascular diseases, such as an impaired lipid profile."
"In other words, PCOS per se is not an indication for statin therapy."
"PCOS Is Not 1 Disease"
Antoni Duleba, MD, who recently coauthored a study showing benefits from simvastatin over metformin in improving ovarian hyperandrogenism at 6 months, said that the study has some notable caveats, including the number of patients and the inconsistencies in the insulin resistance results.
"The study used oral and IV tests, and according to one [test], there was a worsening, but according to the IV results, there was not, and usually people consider IV tests superior to oral tests; so, it's difficult to extrapolate that information."
Furthermore, the use of just 1 type of statin suggests that only part of the story may have been told, he noted.
"Patients may respond differently to different statins. Atorvastatin, for instance, is a hydrophilic statin that usually acts in the area of the liver, whereas simvastatin is lipophilic and has a greater effect on peripheral tissues," said Dr. Duleba, a professor of obstetrics and gynecology at the University of California, Davis.
Dr. Duleba is involved in ongoing cell culture studies comparing statins and how they may affect PCOS.
"There are very significant differences, and some may relate to the fact that water soluble statins are not well absorbed by peripheral tissues, which do not have transporters for statins. Fat soluble statins can meanwhile cross membranes without transporters and therefore act both at the level of the liver and peripheral tissues."
He underscored the importance of studies like Dr. Tapanainen's, however, in helping to advance the understanding of the issue.
"It's good that this study came out because it forces us to look at those issues closer and design studies that help us better identify who is most likely to benefit and who is not and which statins are ultimately the best."
"We need to have larger groups of patients comparing different statins in the same population so that we can fine-tune our approach instead of generalizing 1 finding from 1 group to all populations."
"PCOS is not 1 disease — it's a group of different diseases, and hopefully within the next decade we can identify which phenotypes are likely to benefit from statins as opposed to diet as opposed to metformin."
Dr. Tapanainen and Dr. Duleba have disclosed no relevant financial relationships.
American Society for Reproductive Medicine (ASRM) 68th Annual Meeting. Abstract O-6. Presented October 22, 2012.
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Cite this: PCOS: Impaired Insulin Sensitivity From Atorvastatin - Medscape - Oct 30, 2012.