Women who take certain kinds of oral contraceptives may be at an increased risk of coronary heart disease because of the pills' effect on cholesterol levels, according to a report published today in The New England Journal of Medicine.
A large-scale study, conducted by the Wynn Institute for Metabolic Research in London under contract to the National Institutes of Health here, found that some older kinds of birth-control pills with high levels of a synthetic hormone called progestin can produce changes in blood chemistry resembling those in persons at high risk of cardiovascular disease.
Those changes include elevated concentrations of low-density lipoprotein (LDL) cholesterol, the so-called "bad" cholesterol that clogs blood vessels, as well as reduced quantities of high-density lipoprotein (HDL) cholesterol. Low levels of this "good" cholesterol are associated with premature coronary heart-disease, particularly in women.
"What this study basically shows," said Jeffrey Perlman, chief of the contraceptive evaluation branch of the National Institute of Child Health and Human Development, which funded the research, "is that lowering the level of progestin minimizes metabolic side effects."
For women who take the pill, he said, the research should "get that issue onto the table for discussion between patients and clinicians" when weighing birth-control alternatives. Women, he said, "really need to be saying that they would like to take the lowest dose pf progestin possible."
Most oral contraceptives contain a combination of two common reproductive hormones, estrogen and progestin. Following repeated studies suggesting that estrogen promotes heart attacks by making blood clot more readily, estrogen doses in birth-control pills have been reduced over the past 20 years.
The British project, which examined more than 1,000 women using one of nine different oral contraceptives, is likely to have a similar effect on the pill's other principal component, progestin. It found that "a reduction in the dose of progestin and a change in the type of progestin can bring about a substantial reduction" in heart-disease risk. Two high-dosage formulations using types of progestins widespread in the United States -- norgestrel and norethindrone -- were associated with reduced HDL cholesterol levels in some users, an effect that was offset at lower doses.
The Wynn study and similar NIH-funded projects, Perlman said, is expected to aid in an "effort to reduce the level of drugs used in today's pill so as to minimize side effects."
The new research is not expected to affect the fate of Norplant, a subcutaneous progestin-only contraceptive slated for approval soon by the Food and Drug Administration. The implants are designed to release the hormone directly into the bloodstream instead of passing through the liver, where the cholesterol effects of oral contraceptives arise.
Bruce Stadel, chief of the FDA's epidemiology branch, said the quantities of progestin released by Norplant are comparatively small. "It's enough to affect contraception, but not enough to produce the same kinds of metabolic changes. When administered by mouth, you have to take a lot more because it's degraded in the liver. But when it's released directly into the bloodstream, you don't have to take as much in the first place."