“Does the pill cause depression?” the news headline asked. Prompted by a recent study that described a link between taking birth control pills as a teenager and depression in adulthood, the news got some doctors hopping mad.
Early research hints that there are reasons to look more closely at hormonal birth control’s side effects. But so far, the link is less than certain. “This is a premature connection,” says pediatrician Cora Breuner of Seattle Children’s Hospital.
Putting too much stock in preliminary evidence may lead to fewer teenagers getting birth control and, in turn, more unwanted pregnancies among teens — a situation that can upend young lives, Breuner says. Headlines that frighten teens, their families and doctors are “yet another barrier in place for accessing a completely effective way to prevent unplanned pregnancies.”
Ob-gyn and contraception researcher Katharine O’Connell White agrees. “Birth control gets all of the worry and concern,” says White, of Boston University School of Medicine. “But we know that other things are much more dangerous.” Teen pregnancy, for instance. Access to effective birth control is vital for sexually active teenagers, the doctors say.
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“I don’t think the evidence is there right now to say that this is a threat,” adds epidemiologist and public health researcher Sarah McKetta of Columbia University, who has studied birth control use in teens. Still, she sees value in more research on the issue. “Women deserve good medication … that’s not giving them problems.” If there are risks that come with the pill, then scientists ought to get a handle on them.
Easier said than done. Existing studies can’t quite answer the question at hand, so their results can be interpreted in different ways. Getting an answer is important. In the United States, 42 percent of teenage girls — 4 million in total — have had sexual intercourse, estimates suggest. And an estimated 56 percent of sexually active girls ages 15 to 19 have taken hormonal birth control pills. In the search for clarity, research may illuminate scientific mysteries, including how biology and personal experience combine to shape a teenage girl’s brain in ways that scientists don’t yet understand.
The advent of hormonal contraceptive pills was revolutionary. Starting in the 1960s, women began controlling their fertility — and their lives — in ways that were previously impossible. The daily dose of hormones, cleverly engineered to dupe the body into thinking it’s already pregnant so that a real pregnancy won’t happen, is so iconic that even today, it’s the one medicine known simply as “the pill.”
And it prevents pregnancy remarkably well. With the exception of rare risks, such as blood clots, the pill doesn’t seem to cause much trouble for most people. Its uses have expanded beyond its primary job of suppressing ovulation. About a third of teen pill prescriptions are for noncontraceptive reasons: to ease painful or irregular periods, endometriosis, acne and other conditions.
But every so often, a study crops up that raises a potential red flag. That happened this summer with a report that women who had taken the pill as teenagers were more likely to develop depression as adults. The study, published online August 28 in the Journal of Child Psychology and Psychiatry, asked 1,236 U.S. women, ages 20 to 39, to remember when they began taking hormonal birth control pills. Researchers also asked about the participants’ current depressive symptoms.
A potentially worrisome trend emerged: Use of the pill in the teenage years was linked to higher rates of depression later. At the time of the study, 16 percent of the women who had taken hormonal birth control as teenagers met the criteria for clinical depression. Only 9 percent of women who began taking the pill as adults met the same criteria for depression. For women who never had used birth control, the number was 6 percent.
Those differences among the groups were “really quite substantial,” says study coauthor Christine Anderl, a psychologist at the University of British Columbia in Vancouver. “There might be a long-lasting relationship between birth control use and depression later on,” she says.
Take note of that “might.” Anderl is careful and up-front about the study’s limitations. The results turned up a correlation, not a causal relationship, she emphasizes. The researchers used a statistical approach to make the comparison groups more similar, evening out the differences in education, for instance, that might affect depression rates. That method, called propensity weight scoring, “isn’t perfect — nothing in statistics can make the comparison between groups crystal clear — but it’s a skillful way of dealing with the problem,” says Regina Nuzzo, a statistician at Gallaudet University in Washington, D.C.
Anderl and colleagues used the method to control for other explanations for depression, including smoking, age of first sexual behavior, education, body mass index and so on. But it’s possible that another factor, unknown or just not considered in this study, could be to blame. “We tried to control for everything else that we thought would be an alternative explanation for the link, but that doesn’t mean we didn’t unintentionally miss [something],” Anderl says.
Other limitations further cloud these results (as well as the results of many other studies that assess people’s behaviors and health). The women were asked to remember when they started taking the pill — and memories can be hazy. What’s more, the authors didn’t have information about what kinds of hormonal pills the women used, how consistently they used the pills or for how long — all crucial information, Breuner says.
Hormonal birth control pills come in two main types: the older type, which contains a mixture of estrogen and progestin (a synthetic form of progesterone), and the “mini pills,” which contain only progestin in small amounts. To understand what these pills might do to the developing brain, the type and amount of hormones matter, Breuner says. These caveats, along with others, make her skeptical that there is a true association between birth control pills and depression later in life, she says. “I’m not ready to stop prescribing.”
Two other studies have linked oral contraceptives with depression during the teen years, as opposed to later in life. A study published online October 2 in JAMA Psychiatry found a link between the pill and depressive symptoms in 16-year-olds in the Netherlands. Girls on the pill reported crying more, sleeping more and having more eating problems than girls not taking oral contraceptives.
The second study, of over 1 million Danish teenagers and women, found that teenagers ages 15 to 19 taking birth control pills were more likely to also have prescriptions for antidepressants at the same time. The effect was strongest for teens taking progestin-only pills. That study’s size gave it a “powerful enough lens to spot even a small effect,” Nuzzo says. It was published in 2016 in JAMA Psychiatry.
Now consider a dissenting report. McKetta and Columbia epidemiologist Katherine Keyes studied 4,765 U.S. adolescents and found no evidence that birth control pills influence depression, neither at the time of taking the pill or afterward.
That study, published in January in Annals of Epidemiology, looked at teenagers’ current or prior use of birth control pills, and used interviews to gather information about depression. “Any way we looked at it, we found no effect,” McKetta says.
Like every other study on people, this one comes with limitations. As with Anderl’s study, researchers asked teenagers to think back and remember information, which isn’t foolproof. Parents were also interviewed about their children’s depression, and wishful thinking might have tempted them to fudge answers, particularly to sensitive questions. Those caveats could have hidden an effect, Nuzzo says.
As a whole, these studies — all imperfect, all beset by their own limitations — offer little clarity on whether and how these birth control hormones are changing the brains of teenagers.
Yet, the idea is plausible. The teen years are important for brain development. Hormones such as testosterone, estrogen and progesterone during adolescence can change the brain’s development. “It is a fact,” says Cheryl Sisk, a neuroscientist at Michigan State University in East Lansing.
Her certainty comes from a large collection of research on lab animals, and a slimmer set of human brain studies. In experiments on lab animals, scientists can exquisitely control the timing and levels of hormones and then see what happens to the brain as the animals grow. Female mice, for instance, with ovaries removed before the mice reach adolescence, had differences in learning abilities during adulthood.
Human studies hint that estrogen affects adolescent girls’ brains, too. A genetic disorder called Turner syndrome can leave girls with very low levels of estrogen. Girls with the disorder have differences in the volume of certain brain regions, small studies show. (Testosterone during adolescence can also sculpt boys’ brains.)
It’s possible that hormones delivered in the pill would affect the brain differently than hormones delivered from a teenager’s own ovaries. The timing or the type of hormones would be off, and that mismatch could affect a girl’s brain development, Sisk says.
Derived from cholesterol, hormones like progesterone and estradiol, one of the body’s naturally occurring estrogens, can slip past the blood-brain barrier. “You can almost think about the brain as being bathed in testosterone and estradiol and progesterone,” says neuroscientist Russell Romeo of Barnard College in New York City. These hormones “can get there, and they can affect these cells very intimately,” he says. The hormones can change the behavior of large collections of genes, many of which shape how the brain operates.
But some brain regions are more susceptible than others to the effects of hormones. The hippocampus, the amygdala and select stretches of the prefrontal cortex are still developing during puberty, and all have been linked to depression. Those regions are loaded with molecules that sense estrogen and progesterone, and respond by kicking off a host of cellular changes when the hormones reach the brain.
Set against this backdrop of research mainly in lab animals, the idea that hormones during adolescence could change the brain, particularly in a way that could influence depression, makes sense. But just because something makes sense doesn’t mean it’s true.
To really answer the question well, what’s needed are large head-to-head comparisons of teenage girls randomly assigned to take either hormonal birth control or a placebo, and then monitored for depression years later. But that study will never happen. Research ethics would prevent teenagers who need birth control pills from being given a sugar pill substitute.
Clues might come from other places. McKetta mentions Colorado, where changes to public health policies since 2009 have made birth control options widely available — “any kind you want, wherever, whenever,” she says. In areas near the Colorado clinics that provide birth control, teen birth rates are down 20 percent, according to recent data from the nonprofit National Bureau of Economic Research. The girls who take advantage of access to the pill may be a valuable source of long-term mental health data. “We may be able to completely put this to bed, or we’ll find longer-term differences,” McKetta says.
Meanwhile, Anderl and her colleagues have begun enrolling young teen girls for a study that will span three to five years. The researchers will measure the girls’ hormone levels, monitor their birth control use, assess their emotional health and look for signs of depression. This forward-looking study gets around some of the problems that dogged earlier reports. For one thing, objectively measuring symptoms as they unfold over time means that researchers won’t have to rely on participants’ memories.
“Access to birth control is a universal human right,” says Anderl, who doesn’t want her results to be used to limit access to birth control by politicians, doctors, parents or even young women themselves. The data are too preliminary to be used to make the case against the pill’s use by teenagers, she says.
For a sexually active teen, the hypothetical risk of depression is dwarfed by the known and potentially severe risks of pregnancy, says White, of Boston University. The comparison of risks here is everything: The alternative to reliable contraception is pregnancy, she says. “When you’re looking at media coverage, that is not a point that gets made very often.”
A teenager having unprotected sex has an 85 percent chance of getting pregnant within a year, a condition that comes with many known risks, including depression. “Pregnancy is so much more dangerous than birth control, across the board, full stop, for everyone,” White says.