The study, led by epidemiologist Victoria Holt, Ph.D., M.P.H., a member of Fred Hutchinson's Public Health Sciences Division, is the largest case-control study of its kind to examine the link between body-mass index and oral-contraceptive failure. The research was conducted in collaboration with Delia Scholes, Ph.D., a senior investigator at the Center for Health Studies at Group Health Cooperative in Seattle.
"The results of our study represent yet another reason why obesity is a health hazard," Holt said. "Overweight and obese women have a significantly higher risk of getting pregnant while on the pill than women of normal weight, and this translates into a substantial number of unplanned pregnancies." Among 100 women taking oral contraceptives for a year, Holt's study suggests that an additional two to four women will get pregnant due to being overweight or obese.
"This higher risk of pregnancy also translates into a higher number of obesity-related complications of pregnancy, which range from gestational diabetes and high blood pressure to Cesarean delivery," Holt said.
Body-mass index, or BMI, is a measure of body fat based on height and weight. The World Health Organization divides BMI into four categories for both men and women: underweight (18.5 or lower), normal (18.5 to 24.9), overweight (25 to 29.9) and obese (30 or greater). A BMI calculator is available on the National Institutes of Health Web site at http://nhlbisupport.com/bmi/bmicalc.htm
"We found little difference or variation in the risk of contraceptive failure among women who fell into the first three quartiles of body-mass index, but the risk jumped up dramatically among women in the fourth quartile," said Holt, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine.
Holt and colleagues found the association between extra pounds and pill failure first surfaced among overweight women whose body-mass index was 27.3 or higher, which is equivalent to a 5-foot, 4-inch woman who weighs 160 pounds or more. These women faced a 60 percent greater risk of getting pregnant while on the pill. Those considered obese, with a BMI of 32.2 or greater, faced a 70 percent greater risk.
While no one knows for sure why overweight and obese women experience a higher degree of oral-contraceptive failure than their thinner counterparts, several biological mechanisms could account for the effect.
One possible explanation is increased metabolism. "The more a person weighs, the higher their basal metabolic rate, which can shorten the duration of a medication's effectiveness," she said. Another possibility is that the heavier a person is, the more liver enzymes they have to clear medications from the body, causing a drop in circulating blood levels of the drug. A third theory is based on the fact that the active ingredients in oral contraceptives ? the hormones estrogen and progesterone ? are stored in body fat. "The more fat a person has, the more likely the drug is sequestered, or trapped, in the fat instead of circulating in the bloodstream," Holt said.
Another factor that may account for obesity-related pill failure is that today's oral contraceptives contain relatively low hormone levels compared to those first introduced four decades ago. "Hormone levels have decreased fivefold in an effort to reduce unwanted side effects ranging from weight gain to risk of blood clots and stroke," Holt said. "Today's pill dose is high enough for most women but may not be adequate for all."
So does this mean that overweight women who don't want to risk an unplanned pregnancy should demand a higher-dose pill? Not necessarily, Holt said.
"Overweight women are more likely to have cardiovascular-disease risk factors than normal-weight women, and to increase the dose of contraceptive hormones might increase cardiovascular risks even more," she said.
Instead, Holt recommends that overweight women who have completed childbearing consider a permanent form of birth control such as sterilization, and that overweight women who have not yet completed childbearing consider using a backup form of birth control while on the pill, such the condom or other barrier methods.
Another recommendation for heavy women on the pill is to lose weight, although this study did not specifically examine the impact of weight loss on the pill's effectiveness. "I think losing weight, if one is substantially overweight, is a terrific idea for many health reasons and a laudable goal," Holt said. "I also acknowledge that it is often difficult to do."
For the study, Holt and colleagues compared weight and body-mass index of 248 women who became pregnant while on the pill to an age-matched comparison group of 533 nonpregnant oral-contraceptive users. All of the study participants were enrolled in Group Health Cooperative, a Seattle health-maintenance organization. The women's self-reported history of weight, pregnancy and oral-contraceptive use was verified through medical, laboratory and pharmacy records, which added statistical strength to the study's findings, Holt said.
The U.S. National Institute of Child Health and Human Development funded the study.
Fred Hutchinson Cancer Research Center, home of three Nobel laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, UW Medicine and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 40 nationwide. For more information, visit www.fhcrc.org.
To obtain a copy of the paper "Body Mass Index, Weight, and Oral Contraceptive Failure Risk" by Holt et al, please e-mail the journal at firstname.lastname@example.org.
Obstetrics and Gynecology