Does PCOS increase risk for CVD?

Issue: April 2008

PCOS increases risk but not necesarily mortality from CVD

We have indirect evidence that polycystic ovary syndrome most likely increases the risk of cardiovascular disease, but we do not have a prospective study showing that more women with PCOS die of cardiovascular disease. Because women with PCOS have a number of traditional risk factors for CVD, one could come to the conclusion that most likely they are at increased risk for CVD.

Anuja Dokras

The only studies we have are somewhat circumstantial. In patients undergoing coronary angiography, for example, a study found that the extent of coronary atherosclerosis was independently associated with the presence of polycystic ovaries (Ann Intern Med. 1997;126:32-35). It really does not clearly tell us if these women had a diagnosis of PCOS or not. Another more recent study showed that women who had very irregular periods had a significantly higher risk of fatal and nonfatal coronary heart disease after adjusting for a number of traditional CVD risk factors (J Clin Endocrinol Metab. 2002;87:2013-2017). But an irregular period alone is not the definition for PCOS. So there are studies with circumstantial evidence, but there is no prospective study that has followed a cohort of women for 20 years and looked at the mortality or morbidity rate, secondary to CVD.

An important study that needs to be done is one that investigates whether CVD risk factors that we identify in women with PCOS ultimately result in a higher morbidity or mortality. If not mortality, if it is a higher morbidity, that is significant, because we could more strongly implement preventive strategies in this group and we could counsel them better. Despite the fact that this prospective study has not yet been conducted, I think that physicians should be aggressively counseling these young patients if they identify any of the traditional CVD risk factors, and they should be treating any of these abnormal findings just as they would in any other patient.

Anuja Dokras, MD, is an Associate Professor, University of Pennsylvania Medical Center, Philadelphia.

Women with PCOS at increased risk for CVD

Finally we are at a point where the risk for CVD in women with PCOS is becoming much more pinned down. I was involved in the first study to show that women coming in with coronary artery catheterization are more likely to be hirsute and have central obesity (Fertil Steril. 1990;54:255-259). We evaluated everybody coming in for coronary artery catheterization consecutively, and we found that their waist measurements predicted coronary artery disease, as did any issue of androgen excess by clinical symptom. Birdsall et al in Australia did essentially the same thing, but the patients were a bit younger and they had the luxury of also assessing ovarian ultrasound. What they showed was that women with PCOS are more likely to have confirmed CVD (Ann Intern Med. 1997;126:32-35).

Robert Wild

What caused a lot of controversy was that Wild et al evaluated 1,000 women with PCOS, identified from 54 U.K. hospitals, and did not find a greater risk of CVD. But there are problems with their study. The entrance criteria were that patients had to have histological diagnosis of PCOS by wedge resection, which is basically the ovarian phenotype. This study was missing all the other phenotypes. The researchers tracked from this wedge resection data 786 women through the National Health Service Registry and could only come up with 70 deaths through 1999. The mean age of patients was 57 years, but heart disease is an older-age phenomenon, so they were studying people too early. The researchers could find no difference in the standardized mortality ratio, but they did find a significant difference for diabetes. We should not say this study defines that there is not a greater risk. Fifty-three percent of cases were lost to follow-up.

A recent NHLBI study by Shaw et al evaluated 104 women with irregular menses before menopause and current biochemical evidence of androgen excess. Just like we found in 1990, women with PCOS had more angiographic coronary artery disease than controls. But what they could do that we could not is follow those women over time and figure out who died. They found that women with PCOS were less likely to survive and were more likely to have cardiovascular events (J Clin Endocrinol Metab. 2008;10.1210/jc.2007-0425).

Robert Wild, MD, PhD, MPH, is a Professor of Reproductive Endocrinology at Oklahoma University Health Sciences Center in Oklahoma City.