Why Birth Control Side Effects Have Eluded Science

In August 2021, Emilie Skoog lay on the couch in her parents’ living room, thinking that not a single thing in the world sparked joy. For weeks, the 25-year-old MIT graduate student had been unable to muster enough appetite to eat properly. Instead, she’d spend full days lying in bed, drifting in and out of sleep between sips of Gatorade.

The depression had set in about two months earlier, Skoog said, just after she’d started taking hormonal birth control pills to ease the debilitating cramps she experienced around the time of her period, which rendered her housebound for a few days each month.

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“I’m a very upbeat, happy person,” Skoog said. But that first month taking the pills, she recalled, a fog of exhaustion and apathy replaced her usual cheerful mood. When she walked to the lab where she worked, she added, “I didn’t even care to look both ways across the street.”

Skoog says her doctor diagnosed her with depression and prescribed antidepressants that helped her get off the couch and back to her life. But it wasn’t until she followed the advice of a friend, who suggested she try going off the birth control, that the depression truly lifted, she said: “I swear to you, the day I stopped taking it, I literally felt completely normal.”

Oral contraceptives were approved in the 1960s, and since then, studies suggest, the medications have benefitted large segments of society. Still, concerns about possible side effects linger. Researchers have looked for a connection between hormonal birth control and mental health issues like anxiety and depression. But despite the stories like Skoog’s that circulate on social media, in sisterly social groups, and in doctors’ offices, these studies have not consistently supported a link. For now, while the connection between birth control and mental health may seem obvious to many of the drugs’ users, a true link remains elusive to researchers.

Hormone-based birth control works primarily by mimicking key aspects of pregnancy. At the end of each monthly cycle, people who menstruate have natural hormonal lows that tell their bodies they’re not pregnant. Birth control keeps hormone levels high, as they are during pregnancy, with one consequence being that eggs stay locked away where they can’t be fertilized.

There’s ample reason to believe that tinkering with sex hormones might affect a person’s mood. Conditions such as anxiety and depression often manifest during puberty and menopause, when hormones are undergoing natural fluctuations. When birth control first came on the market, it didn’t take scientists long to begin studying whether these new drugs could also influence their users’ psychology. But in 2018, when researchers from Ohio State University looked at 26 studies examining the link between some of the most common types of birth control and depression, they wrote, “the preponderance of evidence does not support an association.”

Brett Worly, an OB-GYN based in Columbus, and one of the authors of the meta-analysis, said that performing the study changed how he talks to his patients. Before, he cautioned prospective birth control users that the drugs might cause depression — because some reports indicated this might be the case — but now he tells them that’s unlikely. Worly admits, however, that his advice is based only on the best evidence that’s available right now. The study he’d like to see has yet to be done.

“It would have to be like hundreds or maybe thousands of women over at least six months to a year,” he said. Ideally, the study would be performed by independent researchers unaffiliated with pharmaceutical companies, to avoid any bias. Participants would be randomly assigned to take birth control or placebo pills, and researchers would periodically assess depression, anxiety, and a range of mood changes.

But this gold standard approach has a downside for participants: The placebo group would be susceptible to unwanted pregnancies. Participants would need a secondary, non-hormonal form of birth control, but here the options are limited. A copper intrauterine device, or IUD, is the obvious choice for its effectiveness, but insertion is invasive, and heavy, painful periods can be a common side effect. Condoms are an option, but barrier methods are prone to human error and tend to be less effective than hormonal contraceptives. “It’s a hard study to do,” Worly said. “Hopefully, eventually, that would happen. It hasn’t happened yet the way that we need it to.”

Even a group with the capability to complete the study would face an additional challenge: Scientists say they lack the tools to accurately assess many of the mental health side effects that birth control users may experience. Worly and his co-authors focused their meta-analysis on depression because it’s a specific, widely studied condition that researchers have standard ways of diagnosing. The main symptoms of depression include feelings of worthlessness, hopelessness, and fatigue, but birth control users have reported that the drugs can make them cry more easily, feel anxious, or feel oddly emotionless — conditions that are assessed by some depression questionnaires, but which don’t qualify as depression on their own.

Women’s health physician Ellen Wiebe runs an abortion clinic in Vancouver, British Columbia, where she often has conversations with her patients about why birth control failed them. “Over and over again, I had heard that she tried birth control,” Wiebe said, “and she went crazy.”

She asked her patients what they mean when they say they feel crazy. “They told me that they would get angry more easily, that they would cry more easily, that they would just overreact to stuff,” Wiebe said. And so she designed a survey to examine these subtle mood changes. The rate of mental health side effects that she uncovered was far higher than the rates she was used to seeing in physician manuals— of the 978 respondents in the self-reported survey, 51 percent had experienced at least one negative mood-related side effect.

Wiebe said she thinks her research uncovered such a high rate because she designed her survey around the side effects that birth control users reported to her, like disinterest in sex and irritability. And she noted that even comparatively mild mood changes can have a serious impact on well-being: “A combination of being angry and not wanting to have sex is not good for relationships,” Wiebe said. “I remember one woman telling me, ‘I lost the love of my life.’”

Wiebe’s results may not hold for all populations, however. She and her collaborators recruited participants in doctors’ offices, “so right there you have some selection bias,” Andrew Novick, a reproductive psychiatrist at the University of Colorado, wrote in an email to Undark. Women who feel well on their medications are less likely to visit a doctor than those who are experiencing negative side effects.

Worly says he thinks the survey is a nice contribution to scientists’ understanding of mood-related side effects. But he cautions that asking participants to remember how they felt, potentially years earlier, as the study’s authors did, could introduce recall bias. And a critical component of his ideal experiment was missing: “There was no ‘control group,’ to correct for other circumstances that may have affected women, like change in seasons, change in relationship, and more,” he wrote.

Lorraine Boissoneault, a journalist from the Chicago area, knows how hard it can be to disentangle mental health side effects from other factors. She struggled with mood swings from the time she started taking birth control until she switched to a non-hormonal IUD, around six years later. “In my head, the thing that had changed, that seems like the obvious change, was birth control,” she said. But during that same period, she noted, her personal life improved and she started getting treatment for a thyroid condition that had gone undiagnosed.

Novick says he’s treated people who, like Boissoneault, experience mood swings while on birth control, people who experience more subtle changes, and people who actually feel better while taking these drugs. Further complicating the matter, anecdotes suggest that the same person can experience both ends of this emotional spectrum. Elizabeth Hinnant, a writer from Atlanta, found that one form of hormonal birth control left her feeling severely irritated, while another made her feel calmer than usual.

Variability, lack of specificity, and confounding circumstances make mood changes hard to measure, but Wiebe and Novick also pointed to a problem researchers face when studying any serious side effect — people like Boissoneault, Hinnant, and Skoog probably won’t participate in studies testing drugs that they believe made their lives miserable, so studies don’t capture this segment of the population. “It’s something called the survivor effect,” Novick said. Most studies are limited to studying women who are willing to take hormonal birth control. “And who are those women?” Novick asks. “Those women are the ones who want to stay on it.”

Birth control users say they sometimes contend with stigma and dismissive attitudes as they try to address mood changes. Skoog says she consulted two doctors about whether birth control could be contributing to her depression. Both told her that was unlikely. Boissoneault, meanwhile, never talked to a doctor about her mood swings because, “I was scared of what people might say, or how they might react,” she said. “So I kind of just gritted my teeth and tried to get through it.”

Compounding the problem, some researchers may hesitate to speak out against drugs that have had undeniably positive impacts for large segments of society. One study found that the introduction of birth control correlated with a three-fold increase in the number of women enrolled in medical and law school. Another found that birth control may have helped narrow the wage gap. And studies consistently show that children are less likely to grow up in poverty when their parents have access to birth control. These gains were hard fought in the U.S. — the battle to keep birth control accessible has reached the Supreme Court multiple times. Novick remembers showing a colleague his first grant proposal to study birth control’s mood-related side effects. “He was like, ‘You got to tread carefully here,’” Novick said. “Because OB-GYNs are gonna get very defensive.”

Some scientists think outdated views about physiology have also stymied research. Nafissa Ismail, a neuroendocrinologist at the University of Ottawa, said, “We’ve been studying the brain as its own entity for the longest time in the field of neuroscience and forgetting that it belongs to a body.” It’s only recently that a push to reconsider the body has prompted questions about how drugs targeting the uterus can translate to the brain, she added.

Medical imaging suggests that there may be significant translation from body to mind. Using brain scanning techniques like magnetic resonance imaging, researchers have observed that birth control may alter the number of cells — and the number of connections between them — in certain regions of the brain. These alterations may underly behavioral changes observed by Ismail and others, like differences between how birth control users and non-users respond to stress.

Ismail says that resources for this type of work are becoming more available — she cites the Canadian Institutes of Health Research and the U.S. National Institutes of Health as funding agencies that have expressed interest in research on birth control and mood. But after so many years of languishing in obscurity, these fields lack the number of researchers necessary to make rapid progress.

Meanwhile, Skoog said she’s off hormonal birth control for good, and considering acupuncture to control her cramps. She’s also helping friends track their own moods, just in case birth control skews their feelings into dangerous territory. “I imagine that there are many, many, many women out there who are going through this,” she said.

Saima May Sidik is a freelance science journalist based in Somerville, Massachusetts. Her work has appeared in Hakai Magazine, Smithsonian Magazine, Nature, and elsewhere.