When the oral contraceptives Yasmin and Yaz came on the market in 2001 and 2006, respectively, they were thought to be safer than other birth control pills because they contained a different kind of synthetic progestin.
But in a flurry of lawsuits against the pills' maker, Bayer HealthCare, attorneys claim that the progestin contained in the pills, drospirenone, is the cause of health problems, including deep vein thrombosis (blood clots in the deep veins), strokes, heart attacks and gallbladder disease.
As of mid-February, about 1,100 lawsuits had been filed in the United States against Bayer, which stands behind the safety of the pills.
Research on the issue is divided. Some studies have found drospirenone to pose no greater health risk than other birth control pills; some studies show a sixfold greater risk of getting blood clots, even in young, healthy women. More research is being performed on the safety of the contraceptives, but for now, women considering taking the pills will need to weigh the contradictory information themselves.
"There is reason to be concerned, I believe, about both of them [Yaz and Yasmin]," said Dr. Sidney Wolfe, founder and director of Public Citizen's Health Research Group, a nonprofit advocacy organization based in Washington, D.C. "When evidence like that comes up, people should pay attention to it."
Oral contraceptives control unwanted pregnancies by using hormones that block ovulation. The first of these pills, introduced in the United States in the early 1960s, contained high doses of estrogen. They were quickly found to raise the risk of stroke, blood clots and heart attacks.
Second-generation pills introduced in the 1970s contained lower amounts of estrogen combined with synthetic progestins, including one called levonorgestrel. These reduced the risk of blood clots but caused side effects such as weight gain and acne in many women.
The 1980s brought third-generation pills containing different synthetic progestins, such as one called desogestrel. These were later found to be associated with a higher risk of deep vein thrombosis and pulmonary embolism.
The fourth-generation pills — Yaz, Yasmin and Ocella, a generic version — contain estrogen and yet another progestin, drospirenone. They were created not just to prevent pregnancy but to also reduce the side effects of previous pills and to treat premenstrual dysphoric disorder (severe cases of depression, anxiety, headaches and other symptoms).
Yaz is now the No. 1-selling birth control in the United States, grossing more than $391 million in the first half of 2009, up 44% from the same time period in 2008, according to health data provider IMS Health. Bayer received a warning from the FDA last year for overstating Yaz's effectiveness in treating PMDD and acne while minimizing the risks of the medication on its website and television commercials. In response, the company altered its advertising.
Now the contraceptives are not just the subject of lawsuits, they're also under scrutiny by groups such as Public Citizen over their safety. The FDA is testing the safety of Yaz and other pills in an ongoing study.
Two 2009 reports helped raise alarms. Published in the British Medical Journal, both assessed whether drospirenone is more likely to cause blood clots than other types of synthetic progestins.
One study looked at blood clot rates in Danish women ages 15 to 49 with no history of cardiovascular disease. From 1995 to 2005, there were 4,213 cases of various kinds of blood clots including in the heart, kidney, lungs and liver, 2,045 of which occurred in users of oral contraceptives. Researchers found that pills containing the progestins desogestrel, gestodone and drospirenone (the one found in Yasmin, Yaz and Ocella) were associated with a higher risk of blood clots than those containing levonorgestrel.
A second studied more than 3,200 women from the Netherlands. In this case, participants taking birth control pills containing levonorgestrel had a four times higher risk of getting blood clots than women taking no birth control, and for other progestins the risk was higher still: 5.6 times greater for gestodone, 6.3 times greater for drospirenone and 7.3 times greater for desogestrel. The greatest risk occurred during the first three months of oral contraceptive use.
"It clearly concludes that the safest thing to do is take the older [birth control pills], not the third generation or Yaz," Wolfe said.
Public Citizen had already placed Yasmin on its "Do Not Use" list because it can raise blood potassium levels, Wolfe added.
Rose Talarico, deputy director of external product communications for Bayer, said in an e-mail that Bayer "will defend itself vigorously against these lawsuits" and that patient safety is important to the company. She said the company's drospirenone-containing oral contraceptives "are safe and effective when used according to the product labeling."
Two studies, both sponsored by Bayer, found drospirenone to be as safe as other progestins.
In one, scientists at the Center for Epidemiology and Health Research in Berlin tracked for over a year more than 58,000 European women who had been prescribed various forms of birth control pills. They concluded that there was no greater risk of mortality, cancer or cardiovascular problems from pills with drospirenone than other oral contraceptives.
In the other, i3 Drug Safety, a company that provides pharmaceutical services to drug companies, followed for seven months almost 70,000 U.S. women taking various kinds of oral contraceptives, including ones containing drospirenone. The researchers concluded that more than 9,000 women would need to take Yaz or Yasmin for one extra case of deep vein thrombosis to occur.
Attorney A.J. de Bartolomeo, a partner at the San Francisco law firm Girard Gibbs who is helping shepherd lawsuits against Bayer, said women should be warned if there is even a slightly greater risk.
"We believe it's a dangerous drug, and the most important thing here is to allow women to make an informed choice and know what the comparable risks are before they put a drug in their body," De Bartolomeo said.
As of November, the Food and Drug Administration had received reports of 993 cases of pulmonary embolism (blood clots in the lungs), 487 of deep vein thrombosis (clots in the deep veins) and 229 of other blood clots for the two medications combined.
Some physicians think the attention the medications have received serves only to frighten women.
"Patients get hurt with these types of lawsuits," said Dr. Andrew Kaunitz, a professor of obstetrics and gynecology at the University of Florida's College of Medicine who has consulted with pharmaceutical companies, including Bayer. "They get scared not only with this one pill but all types of contraceptives."
Kaunitz said all types of oral contraceptives increase the risk of blot clots three- to fourfold. But, he added, pregnancy increases the risk of blood clots six- to 10-fold. He said he wouldn't recommend patients change their pills if Yaz or Yasmin are working well for them.
Dr. Anitra Beasley, a physician at the Leadership Training Academy of Physicians for Reproductive Choice and Health and a fellow at Columbia University in New York, has been telling her patients the same thing. She said many come in with worries after seeing commercials questioning the pills' safety — and that some have stopped taking Yaz only to return with an unwanted pregnancy.
"We've got great news from the FDA, that has looked at all of these studies and assures us that the best-done study shows that the risk of clots with Yaz is not greater than on any other birth control pill," she said. "And we have read all of the same literature and have come to the same conclusions — we didn't change our practices."
Dr. Anita Nelson, a professor of obstetrics and gynecology at UCLA's David Geffen School of Medicine who serves on the advisory board of Bayer, said the litigation runs the risk of "scaring the heck out of women."
"I have noticed a pattern, that every time a method of birth control gets popular it gets sued," she said. "The same thing happened for the patch; and we lost Norplant [for the same reason] even though it was very safe and effective."