The only way to know whether a symptom already prevalent in everyday life is provoked or made worse by a drug is to do a controlled trial in which women are randomly assigned to take either contraceptive pills or a placebo. It's tricky to recruit women for the placebo arm of a birth-control trial, but researchers have managed to complete three such studies, involving a total of more than 1,200 women total. These were designed to test the pill's ability to reduce acne or menstrual pain, but the researchers also gathered data on rates of headache, nausea, breast tenderness, vomiting, and weight gain. They found no significant differences in any of these among women who took birth control pills and those who got a placebo. (The pill's most common side effects are, in fact, spotting and bleeding in between periods.
The perceived link between birth-control pills and weight gain actually goes back to America's very first contraceptive, a combination pill called Enovid. When Enovid was approved as a contraceptive in 1960, it came with a booklet noting that "weight gain or loss occurs occasionally. If you should gain weight and it is objectionable to you, control your diet and use less salt." Indeed, many women thought that Enovid was making them gain weight but stayed on it anyway because they loved having spontaneity in their sex lives without the worry of pregnancy, says Andrea Tone, author of Devices and Desires: A History of Contraceptives in America.
It's not clear whether Enovid, which contained a far greater dose of hormones than today's pills, actually made women plump, but once the idea that it provoked weight gain took hold, it became a self-fulfilling prophecy. The power of suggestion is extraordinarily potent, and telling women that the pill might cause weight gain (or nausea or breast tenderness) can make those side effects appear. Scientists call this the nocebo effect. We know that expecting a sugar pill to improve your health can invoke a beneficial placebo response, but expectation works the other way, too. Ask people to remain alert for a symptom, and they're more likely to see it. In one study from 2007, about 100 Italian men with prostate problems were given a commonly-prescribed drug, and half were told that the drug might cause erectile dysfunction and loss of libido. The patients who had been warned about side effects ended up experiencing them at a much higher rate than the ones who never heard about them.
So here's the question: If telling a woman that she might gain weight could actually make her gain weight, why don't the doctors and pharmaceutical companies just keep their mouths shut? Grimes argues that to prevent nocebo responses, nonspecific symptoms like weight gain should be removed from all drug labels unless or until they've been definitively linked to the drug. That's unlikely to happen anytime soon, though. The FDA offers drug companies guidance on which potential side effects to list on a label, and manufacturers tend to go ahead and list any that have shown up in clinical trials regardless of whether they're caused by the drug in question. That way, they can tell any patients who decide to sue that they had been warned.
About half of pregnancies in the United States are unplanned. The pill is not right for every woman, and it has small but important risks, such as the potential for life-threatening blood clots. Even so, taking the pill is safer than being pregnant. Studies also show that women on the pill have significant reductions in the risk for endometrial and ovarian cancers (along with tiny, probably insignificant increases in the risk of cervical and liver cancers). And if you really want to stay trim, birth control pills are a good way to go. When taken as directed, the pill is about 99 percent effective in preventing pregnancy, which is perhaps the world's most reliable cause of weight gain. "About 25 to 30 pounds quite predictably," says Grimes.