Do women with PCOS and an atherosclerotic CVD risk greater than 5% benefit from statin therapy?
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When I see a patient with polycystic ovary syndrome — even young women, with an atherosclerotic cardiovascular disease risk below 5% — I still prescribe a statin because their lifetime risk is so high.
PCOS is an ongoing lifetime challenge for these patients and often leads to diabetes and CVD. When examining the value of statins, you have to consider the lifetime risk for heart disease. Based on new data from genomics, we know that when you have high CV risk over the lifetime, it results in a substantial risk for developing even premature heart disease. In these cases, statins have the proven CV benefit.
We don’t have many options to consider for reducing CV risk in women with PCOS. Fibrates in the ACCORD trial were associated with adverse CV events in this subgroup of women. Niacin is associated with a significant effect on dysglycemia and increasing risk for diabetes. The only viable option is statin therapy. We know from our work with patients with diabetes that statin therapy may be associated with an increased risk for worsening insulin resistance and perhaps some increased risk for worsening diabetes. Overall, however, CV benefit is well-substantiated with statins. If there is a modest risk for insulin resistance worsening, it is well offset by the CV benefit.
We have moved to a 10-year risk-based model for assessing when to use a statin. However, we now also consider the concept of what we call primordial prevention — taking advantage of long-term therapy exposure to reduce lipid levels. We typically think of high-intensity statins for high-risk patients as this kind of paradigm. For PCOS, we know there is substantial, long-term lifetime risk, and you may be better off going with a low-dose statin, taking advantage of the treatment-over-time effect while also minimizing the maybe harmful effects statins might have on insulin resistance over time. This is a good example of how we should think about statin use for these high-risk patients. The new American Heart Association/American College of Cardiology guidelines do mention PCOS as a condition where you want to think about statins for primary prevention because of the high risk for CVD.
Michael H. Davidson, MD, is a clinical professor and director of preventive cardiology at the University of Chicago Pritzker School of Medicine. Disclosure: Davidson reports he consults for Amgen and Sanofi/Regeneron.
Stains are potentially useful in women with PCOS, but we must consider the type of statin and the goal of treatment.
We are talking about prescribing statins for young women of reproductive age for, potentially, the rest of their lives. We simply do not have the data on whether that is going to be beneficial. Not all statins are equal. We have potentially promising data on both CV and endocrine outcomes with some statin therapies in women with PCOS; however, these are short-term data with surrogate outcomes, not clinical, long-term outcomes, which is what we truly need.
Right now, statins are used very rarely in women of reproductive age. Historically, statins have been contraindicated for women at risk for pregnancy, that is, any premenopausal woman. At the same time, we know that women with an adverse lipid profile or elevated markers of inflammation, like C-reactive protein, are at risk for increased CV complications when compared with women with normal lipid profiles. This includes many women with PCOS.
Hydrophilic statins, such as simvastatin, which do not cross cell membranes on their own, are considered safer by many cardiologists because they will act only at the level of organs or tissues that have transporters. A statin that cannot cross the cell membrane is less likely to cause adverse events, such as muscle pain. We have shown that if you are using a lipophilic statin, the effects on ovarian tissues are prominent, even reducing androgen production. We have to ask ourselves whether we are using statin therapy to lower androgen levels or to improve CV risk factors, or both.
If you have a patient with hyperandrogenism, statins should probably not be the first line of treatment. We have other treatments that are well-proven. However, if you have a patient with the combination of hyperandrogenism and an adverse lipid profile and CV risk factors, statins should be considered, but, at this stage, I would say only within the framework of a clinical trial. Larger studies on diverse populations and, ultimately, longer-term outcomes, are needed. We don’t want to just treat the lipid level. We want to know if, long term, we can lower the risk for CV events in these women.
Antoni J. Duleba, MD, is professor and director of the division of reproductive endocrinology and infertility at the University of California, San Diego. Disclosure: Duleba reports no relevant financial disclosures.