Obese women taking oral contraceptives had a 30-fold increased odds for cerebral venous thrombosis (CVT), compared with normal-weight women, in an unmatched case-control study of 186 CVT cases and 6,134 controls.
The association between a body-mass index of 30 kg/m2 or higher and increased odds of CVT “appears to be fully attributable to a strongly increased risk in women who use oral contraceptives [OCs],” said Dr. Susanna M. Zuurbier of the Academic Medical Centre in Amsterdam, and her colleagues.
“Although the relative risks are increased substantially, the absolute risks of CVT are still small,” the researchers said. “Moreover, withholding oral contraceptives may lead to an increase in unintended pregnancies and thus the number of pregnancy-related thrombosis cases.”
After controlling for multiple variables, CVT was 2.63 times more likely to occur in obese individuals, compared with those of normal weight. When the findings were stratified by sex, a BMI greater than 30 kg/m2 had no significant impact on CVT in men, but the odds rose 3.5-fold in women, the investigators reported online March 14 in JAMA Neurology (JAMA Neurol. 2016 Mar 14. doi: 10.1001/jamaneurol.2016.000100).
On further analysis, overweight and obesity had a dose-dependent impact on the odds of CVT among women who used OCs. Adjusted odds ratios were 11.87 for those with BMIs ranging from 25 kg/m2 to 29 kg/m2, and 29.26 for those with BMIs of 30 kg/m2 or higher when compared against normal-weight women who did not use OCs. No association was found between obesity and CVT risk in women who did not use OCs, the researchers noted.
Patients with CVT were recruited in 2006-2014 from two medical centers, one in the Netherlands and the other in Switzerland. The controls were part of the Dutch Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study. Overall, patients with CVT were more likely to be younger than controls (median age 40 years vs. 48 years). They also were more likely than controls to be female (72% vs. 53%), users of oral contraceptives (73% vs. 24%) and have a history of cancer (9% vs. 4%).
The study was limited by several factors, including the small number of CVT cases, the lack of complete BMI data for the study population, and time difference in recruitment of cases and controls, the researchers noted, but they advised clinicians to keep the risk in mind when counseling obese women about OC use.
“Alternative methods of contraception that are not associated with thrombosis, such as an intrauterine device, might be offered to these women,” they wrote.
The study was funded by grants from the Netherlands Organisation for Scientific Research, the Dutch Thrombosis Society, the Remmert Adriaan Laan Foundation, and the Swiss Heart Foundation. Study coauthor Dr. Marcel Arnold disclosed receiving honoraria for giving lectures and serving on advisory boards for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Covidien.