On 28 September 2016, JAMA Psychiatry published a study submitted by Danish researchers suggesting that hormonal birth control might increase the risk of depression among patients:

Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.

Researchers followed more than a million women between the ages 15 to 34 from 2000 to 2013, and results gleaned from 1,061,997 participants suggested that:

Compared with nonusers, users of combined oral contraceptives had an [adjusted incidence rate ratio (RR)] of first use of an antidepressant of 1.23. Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34; users of a patch (norgestrolmin), 2.0; users of a vaginal ring (etonogestrel), 1.6; and users of a levonorgestrel intrauterine system, 1.4. For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 and those using progestin-only pills, 2.2. Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4. When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7.

Senior author Dr. Oejvind Lidegaard said the findings were significant but emphasized that most women prescribed hormonal birth control will not become depressed:

Even though the risk of depression increases substantially with these drugs — a 40 percent increase is not trivial — most women who use them will not get depressed. Still, it is important that we tell women that there is this possibility. And there are effective nonhormonal methods of birth control.

Of the 1,061,997 study participants, 133,000 initiated a course of antidepressants during the course of the study. Lidegaard stated that it’s “always difficult” to rule out all other factors unrelated to birth control in a given depression diagnosis. Experts posited that the findings were not absolute as some important factors weren’t considered in the final outcome of the study:

Three independent experts contacted by STAT all pointed to a flaw in the Danish study: It was designed in a way that makes it impossible to tell whether it’s hormonal contraception specifically — or just the changes in life that drive women to use any type of contraception — that’s driving the increased risk.

“We don’t know why the women on hormonal contraception were given the prescriptions they were, or why they chose the way they did,” said Dr. Jonathan Schaffir, an OB/GYN at Ohio State University … Women who choose to go on hormonal contraception might be doing so to control health problems like menstrual pain or bleeding that could put them at higher risk of depression. They might also turn to birth control because they’re in stressful social situations that would make pregnancy undesirable and also put them at risk for depression.

Several experts said they wished the study had specifically looked at the health outcomes of women using copper IUDs or condoms or other non-hormonal forms of contraception, to see how they compared with women using no contraception and hormonal contraception.

Lidegaard said copper IUDs weren’t tracked in the study because they are free over the counter in Denmark, meaning that they are not tracked in the country’s database. (Condom purchases, of course, wouldn’t be trackable either.) He said it was “unlikely” that the need for birth control was driving the findings.

An expert with whom we spoke echoed the concerns about circumstances not factored into the research:

I’m [concerned] about the article linking depression with the pill scaring people [away] from [Premenstrual Dysphoric Disorder] treatment. The article [did not] specifically [address] PMDD and continuous use, or on the type of progestin used (which matters a lot). It also makes an extremely poor case of the pill itself being causitive, rather than correlative. Its highest correlation was found in adolescents, and one can [imagine myriad causes] for that, not related to the hormones in the pill.

People think the article has something to do with feeling depressed while taking the pill, but that’s not what they examined. They linked the incidence of ending up in a [psychiatric] ward [as] a woman on the pill over many years. Again, there’s dozens of factors at play there.

After the birth control depression risk study was released, experts cautioned patients not to hastily base contraceptive decisions on it. Noting that mood effects were an extant potential side effect advised for hormonal contraception, experts added that “from this study there is no way of linking causation, therefore further research is needed to examine depression as a potential adverse effect of hormonal contraceptive use.”