A recent study published in JAMA Psychiatry launched a thousand ominous articles reporting a confirmed link between depression and hormonal birth control. The finding lends credence to prior research, the side effects section on most prescription birth controls, and years of women’s anecdotal complaints. But most of the viral coverage is using a trick of statistics to dramatize the findings and present a skewed perspective on the actual risks to women’s health.
My feeds were dominated last week by an op-ed published in The Guardian that suggested those who questioned this study were “pillsplaining” with “paternalistic platitudes” designed to squash research findings that benefit women. I suppose one could view my skepticism as part of the vast medical conspiracy to force women to bear the main burden of birth control. From another angle, critiquing research instead of blindly accepting it because you like the punchline is responsible science. If everyone accepted Freud’s research at face value, we’d still think clitoral orgasms were a sign of mental illness.
So I am prepared to pillsplain.
First, the study design. To identify a link between hormonal contraception and depression, researchers at the University of Copenhagen drew on Denmark’s national health registries to analyze an astonishingly large data set: the medical history of over one million Danish women aged 15-34, between 2000 to 2013.
The study investigated whether there was a difference in either the rates of first use of antidepressants or first diagnosis of depression between women users and non-users of hormonal contraception. Because participants in this study were not randomly assigned to take hormonal birth control (they chose to on their own, based on any number of factors), the study can’t claim to have determined any kind of causative relationship.
Researchers found that women using hormonal contraception were overall 20-30% more likely to be prescribed antidepressants for the first time as compared non-users. The relative risk ranged from no change with certain combined pills to a 2.1 times higher rate of antidepressant use in women using the patch. Among adolescents, the numbers were even more striking: they were at a 1.4 - 3.2 times greater risk of being prescribed anti-depressants, with the highest risk found in teens using the patch, ring, and IUD. That all seems staggering, but how do those numbers translate to real life (known as the “absolute risk”)?
Not as impressively, it turns out. Among nonusers of hormonal contraception, 1.7% of Danish women will be prescribed anti-depressants. In users, that number goes up to 2.2%—a 0.5% increase. In adolescents, the numbers amount to an 0.8% increase. The difference is statistically significant, but it’s not exactly a reason for all women to ceremoniously dump their pill packets—just something to think about when they consider which method of birth control may be right for them. It also may not reflect an actual increase in depression. Antidepressants are prescribed for off label uses to treat everything from anxiety disorders and premenstrual syndrome to migraines and chronic pain. Women who use hormonal contraceptives may also be more willing to treat their depression with medication than non-users. The takeaway from this part of the study is that people prescribed hormonal contraceptives are more likely to be prescribed anti-depressants, not that it increases the risk of depression.
A better metric for that would be the second outcome studied: diagnoses of depression made in psychiatric hospitals. The increase in risk is a little lower than first prescription of antidepressants, but still significant. As was the case with antidepressant use, the numbers varied widely with the type of contraception. Among all women, there was a 10-20% increased risk of being diagnosed with depression for women on hormonal contraception. Adolescents on the combined pill were 1.2 times more likely to be diagnosed with depression and those using a progestin-only IUD were more than three times more likely. But the real world numbers?
The eager claims many articles made of sky high increases in depression are decidedly less exciting when you look at them in context. Among women who did not take hormonal birth control, 0.3% were diagnosed with depression at a psychiatric hospital. That number increased 0.05% among users taking combined oral contraceptives. If those numbers seem low, it’s because the study only included severe cases of depression requiring hospitalization—only one in 20 Danish women prescribed antidepressants are referred to a hospital. Because women diagnosed with depression by private therapists were not included in this data, the study likely significantly underestimates the rates of depression in the general population. That makes it difficult to draw conclusions—is this increased risk of depression found only in the most severe cases or is it also reflected in people with more mild depression?
Dr. Julia R. Steinberg, assistant professor at the University of Maryland School of Public Health, points out that the increase in diagnosis and treatment may not be from hormonal birth control but rather that women are being linked to providers. “Women may have had depression before going to the doctor for contraception but they were not diagnosed with it until they came in contact with a provider. The fact that the effect of hormonal contraception was stronger for teenagers supports that idea, since teenagers may have had less contact with a providers that diagnose depression or prescribe contraception.”
It bears mentioning that the control group used here—non-users of hormonal contraception—includes both women who use no birth control and those who use non-hormonal forms like condoms and the copper IUD (which is over the counter in Denmark). To look at the specific risks associated with hormones, users would have to be compared explicitly to women who relied on non-hormonal birth control. It is also relevant whether non-users were connected to the same level of medical care as users. Denmark also has one of the highest rates of both hormonal contraceptive and antidepressant use in the world. These findings may not generalize to other nations.
The study’s authors suggest that the increase in progesterone may responsible for the increased incidences of depression and, for the most part, rates of both antidepressant use and diagnosis of depression were indeed higher in progestin-only products. But the numbers cause some problems. For example, the highest risk of antidepressant use and depression diagnosis was associated with the levonorgestrel IUD (better known in the US as Mirena). But research suggests that the blood level of progestin is far higher with oral medication (also known as the “mini-pill”)—so why a higher risk of depression at 1/10th the level of hormone?
Regardless of the physiology behind it, the increased risk was evident for all women, particularly in teens. The researchers concede that this may be in part because adolescents are more vulnerable to risk factors of depression and it’s certainly worth consideration. A major feature of adolescence is natural hormones wreaking havoc on your mental state, and the study does suggest that there is a small possibility that hormonal contraception could be piling on. But is such a finding worth rethinking the pill or an IUD for women with no known risks for depression? That depends on how you weigh the risks and benefits of taking it.
For example, hormonal contraception is one of the most effective means we have of preventing unintended pregnancies (yes, there are other options, but only abstinence can match the IUD in real-world effectiveness). Dr Øjvind Lidegaard, lead supervisor of the study and clinical Professor in Obstetrics and Gynaecology at the University of Copenhagen, was not overly concerned with this, explaining that “unwanted pregnancy will lead to abortion and those women do not have depression as compared to before. Women who deliver do have an increased risk of depression within the first 3-6 months after the delivery but after that return to normal.” But even if we were to assume that all women have easy and low cost access to abortion or that all women would choose to have one, research suggests he may be significantly underestimating the consequences of unintended pregnancy.
Unwanted pregnancies are associated with increased rates of depression during the pregnancy, postpartum, and later in life (an increase in mental health problems is associated with unintended pregnancy itself, regardless of whether a woman chose to abort or carry the fetus to term). These risks may be even more pronounced in the case of adolescents. Pregnant teenagers are less likely to finish high school and more likely to live in poverty than their peers — two additional risk factors for depression.
Hormonal contraceptives are also used to treat acne, a condition which can be associated with an increase in social anxiety and depression. Some women are prescribed contraceptives to treat dysmenorrhea, a painful disorder that is associated with a negative impact on a woman’s academic and personal life. No finding exists in a vacuum—there’s a pro/con list brewing here unique to every woman.
This study is important, but despite what some headlines want you to believe, it’s not the first of its kind. This is a small part of a decades of research on how hormonal birth control impacts mental health. Some prior studies do reinforce the link between hormonal contraception and depression, but there are others that indicate no difference or even positive effects of hormonal contraception on mood. A less reported part of the present study adds yet another twist. Increased risk of diagnosis of depression among hormonal contraceptive users peaked after six months of use, but after four years of use the risk was actually lower than non-users. Increased statistical risk of antidepressant peaked at three months and then gradually returned to baseline over time.
Dr Lidegaard took issue with some of the criticism that his study received in the press, defending it against claims of inadequate control groups and alternative explanations for his findings, but his take-away was not all that different from the experts who questioned it: “Clinicians and scientists should recognize that this is a substantial risk in the youngest women. All women who are prescribed should get information that it can cause depression and if they get it they should be aware that that’s a consequence. Women deserve proper information about benefits and risks so that they can decide whether it outweighs the benefits to them specifically. Physicians may be more careful about prescribing if a patient has recent depression or actual depression than you should be more reluctant of prescribing.”
People may disagree with the word substantial, but few would argue with the idea that any doctor who prescribes hormonal birth control (any medication) should review the side effects with their patients and emphasize that they should return with any concerns.
The number one reason women give for discontinuing or changing their birth control is changes in mood—this is not an issue that should be taken lightly. If you feel that your birth control is affecting your mood or in any way impacting your life for the worse, talk your doctor. You don’t need research to prove it.
Caroline Weinberg has previously written about science and health at Eater, Vice Motherboard, Aeon, the Washington Post, and a few dry academic publications. You can find her on Twitter @ckw583.