Oral Contraceptives May Increase VTE Risk in Women With PCOS

Damian McNamara

December 03, 2012

Oral contraceptives, largely considered the most effective treatment to relieve symptoms for women with polycystic ovary syndrome (PCOS), might place patients at elevated risk for venous thromboembolism (VTE) events, according a population-based study.

Risk for nonfatal VTE was 2 times greater among 43,506 women with a diagnosis of PCOS who were receiving combined hormonal contraceptives (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.41 - 3.24) compared with 43,506 matched control women who were taking contraceptives but did not have PCOS.

"Physicians should be aware of a potentially synergistic increase in venous thromboembolism risk in women with PCOS taking combined oral contraceptives," Steven T. Bird, PharmD, from the US Food and Drug Administrator (FDA) Center for Drug Evaluation and Research, and associates write in a report published online December 3 in the Canadian Medical Association Journal.

In terms of incidence, women with PCOS had a 23.7 per 10,000 person years incidence of VTE compared with 10.9 per 10,000 person years among matched women in the control group.

Just having PCOS also was associated with an increased relative risk for VTE: Dr. Bird and associates found that women with PCOS but not taking oral contraceptives had a 1.5-fold increased risk compared with matched women without PCOS and no contraceptive use (HR, 1.55; 95% CI, 1.10 - 2.19).

Interestingly, Dr. Bird's study comes on the heels of similar research that reached a somewhat different conclusion, Robert L. Barbieri, MD, chair of the Department of Obstetrics and Gynecology at Brigham and Women's Hospital in Boston, Massachusetts, told Medscape Medical News.

Researchers from the Centers for Disease Control and Prevention (CDC) reported a VTE prevalence of 374.2 per 100,000 among women with PCOS compared with 193.8 per 100,000 among women without it, according to a cross-sectional analysis of a large commercial database from 2003 to 2008 performed by Ekwutosi M. Okoroh, MD, and colleagues ( Am J Obstet Gynecol. 2012;207:377.e1-8).

"Both the FDA study and the CDC study reported that among women with PCOS, there is an increased rate of venous thromboembolism," Dr. Barbieri said. "They are discordant on the next issue. The FDA study says that oral contraceptives increased risk among PCOS women, whereas the CDC study says they do not. That's an interesting discordant finding."

The disparity may be a result of studying different populations, Dr. Barbieri added. In addition, both studies are retrospective and feature some important limitations.

"Clinically they have pointed out an important association that clinicians should be aware of: that polycystic ovary syndrome may be associated with an increased risk of venous thromboembolism. I think that is fair," Dr. Barbieri said. "But I'm not sure that, given the weight of evidence, they've yet established that estrogen-progestin contraceptives further increase the risk in this population."

Dr. Bird and colleagues used International Classification of Diseases, Clinical Modification (ICD-9-CM), codes and claims data to identify patients with PCOS and contraceptive use from 102 managed care plans in the IMS LifeLink Health Plan Claims Database. They analyzed data from May 2001 to December 2009 and included women aged 18 to 46 years.

Potential limitations of the study include a lack of control for some possible confounders such as diet, exercise, or family history of VTE. In addition, use of ICD-9-CM codes to identify women with PCOS may underestimate the true prevalence, the authors note.

The McGill University Health Center, Fonds de la Recherche en Santé du Québec, and the Ministère de la Santé et des Services Sociaux provided an unrestricted grant to support this study. One coauthor served as a consultant for Pfizer and the Observational Medical Outcomes Partnership, one coauthor receives financial support from le Fonds de la Recherche en Santé du Québec, one coauthor receives financial support from the Agency for Healthcare Research and Quality, and one coauthor holds a grant from the National Institutes of Health and is the principal investigator for the Observational Medical Outcomes Partnership, a private–public partnership designed to help improve drug safety monitoring. The other authors and Dr. Barbieri have disclosed no relevant financial relationships.

CMAJ. Published online December 3, 2012.