The popular birth control pills Yaz and Yasmin have attracted a swarm of negative attention the last two years.
The most worrisome allegation against them is that they cause increased risks of dangerous blood clots.
A blood clot that occurs in a large vein - known as a deep vein thrombosis or DVT - can break off, travel to the lungs, strain the heart, and even cause death.
In August 2009, the prestigious British Medical Journal sounded the alarms, publishing two studies that showed the medications to be more dangerous than other birth control pills.
A Danish study claimed that hormones in Yaz and Yasmin caused 64 percent more clots than standard birth control pills. A Dutch study in the same issue showed similar findings.
Bayer, the maker of Yaz and Yasmin, argued that the drugs are perfectly safe, pointing to research the company paid for that found no increased risk.
The studies followed closely on the heels of Bayer's running afoul of the Food and Drug Administration for misleading Yaz advertising.
The FDA accused Bayer of running ads that minimized the drug's risks and overstated its usefulness and efficacy. Bayer agreed to spend $20 million to run a corrective ad campaign.
Lawsuits are piling up.
With controversy at a low boil, should women taking Yaz or Yasmin be worried for their health?
The best current evidence suggests that the two drugs pose no greater risk than other birth control pills. Here's why.
All medications carry some risk. Even an everyday drug like Tylenol can lead to life-threatening liver failure on rare occasions. The Pill is no exception.
Birth control pills prevent pregnancy by combining estrogen and progesterone to prevent ovulation. The estrogen in all types of birth control increases the risk of blood clots. Soon after the Pill came on the market, researchers identified estrogen as the culprit, and manufacturers cut the dose of the hormone. While safety improved, some risk remains.
Whether progesterone in the Pill causes clots remains an unresolved and controversial topic.
Thankfully, DVTs in healthy young women are rare. Even if a birth control pill doubles, triples, or quadruples the chances of a clot, the actual risk remains tiny.
And many women decide the small risks of the Pill are worth the benefits.
Yaz and Yasmin work the same way as other birth control pills, combining estrogen and progesterone.
Concerns center on drospirenone, a new type of progesterone. While Yaz and Yasmin use the same estrogen as older pills, they are the first birth control pills to add drospirenone.
If Yaz and Yasmin were found to increase clots, it would be a good reason to scrap the drugs, and use older birth control pills.
Unfortunately, medical research finds it particularly hard to measure the risk of rare problems. Detecting the rate of an uncommon event, like a blood clot, requires lots of money to fund a large study with tens of thousands of women.
While an increase in risk of 64 percent, the difference found in the Danish study, sounds dramatic, if a medical condition is rare enough, only a few additional women will be affected. Small missteps in a study may hide real risks or exaggerate risk where none exists.
The best example for how scientists can miss the mark occurred just over a decade ago. Research initially found that postmenopausal women on estrogen had fewer heart attacks than women not taking the extra hormones.
Studies comparing the two groups worked hard to account for other causes of heart disease such as smoking, cholesterol, diabetes, and high blood pressure. A top study published in the New England Journal of Medicine in 1996 found estrogen cut heart attack rates in half. Other studies showed similar results.
Doctors encouraged patients to take estrogen, and patients demanded the medications.
Only when researchers performed a major randomized trial, the Women's Health Initiative, did the truth come out: Estrogen increased the risk of heart attacks, blood clots, and strokes. Many women stopped taking the extra hormones overnight.
A close look at the studies on Yaz and Yasmin in the British Medical Journal show they also suffer from major potential shortcomings.
The Danish study failed to include important risk factors like obesity and family history of blood clots, drawbacks that could account for the risk seen. The Dutch study included too few women on drospirenone to reach meaningful conclusions. Details in these two studies hinted at other potential errors.
A European study following 58,674 women controlled for risk factors better and found no increased clots.
Even if the results of the Danish study are borne out, 7,400 women would have to switch from a "high-risk" to a "low-risk" progesterone to prevent just one clot.
The controversy highlights an important problem with the whole drug approval process.
A study that gets a drug approved may include a few thousand patients, not large enough to catch small increased risks.
Only when a drug hits the market and is used by hundreds of thousands or millions of patients can risk be shown. Unfortunately, the FDA lacks the power and resources to make sure this type of postmarket research is done quickly and correctly. The research done on Yaz and Yasmin after approval was actually better than most other drugs.
No matter the final word on drospirenone, the Sturm und Drang surrounding Yaz and Yasmin lawsuits is likely to continue.
Expert witnesses will debate the merits of the medical evidence in court, said Philadelphia lawyer Gregory Spizer. Spizer is representing 100 clients with filed cases, and estimated that Yaz and Yasmin lawsuits number nationally in the thousands.
For a successful case against Bayer, plaintiffs will have to show the company knew about risk and failed to adequately warn doctors and patients properly, leading to harm, said Spizer, who refrained from commenting on his own legal strategy.
How Bayer presented the drugs, and not the medical evidence, may prove to be the focus of litigation.
Bayer marketed Yaz aggressively after studies found that drospirenone improved moderate acne and relieved symptoms of premenstrual dysphoric disorder, the severe form of premenstrual syndrome.
In one TV ad that prompted the FDA warning, a narrator asks, "Did you know there's a Pill that could do more?" Smiling women look up into the sky as balloons labeled "moodiness," "fatigue," and "increased appetite" float away. The commercial promises clear skin as well.
The ads present Yaz as a cure-all even though premenstrual dysphoric disorder affects only a few women, and other birth control pills probably treat acne just as well.
With all the noise around Yaz and Yasmin, it's probably best to remember just one thing: For most women, the drugs will offer risks and benefits no different from any other birth control pills.