Firm evidence is lacking on whether hormonal contraception can cause depression. And experts say a new study, the largest of its kind, doesn’t go very far in making the picture less murky.
Researchers at the University of Copenhagen found that among more than 1 million Danish women, those using hormonal contraception were more likely to be diagnosed with depression or prescribed an antidepressant for the first time, in the subsequent months or years, compared to their peers not using hormonal contraception. Increased risks were found across nearly all types of hormonal contraception, and were highest among adolescent girls.
Many clinicians are familiar with anecdotal reports by women on birth control about mood changes; one common brand, for instance, lists depression as a side effect. But it’s difficult to study the possible link using gold standard research methods because women, understandably, don’t want to be randomly assigned to skip effective birth control. So researchers have had to settle for the next best alternative: following women over time and measuring their health outcomes.
A ‘potential side effect’
The new Danish study was made possible by the country’s famously thorough record-keeping, which tracks each citizen’s prescriptions and diagnoses based on a personal identification number assigned at birth or immigration. That system allowed the Danish researchers to track the cohort of Danish women from 2000 to 2013.
Women on hormonal contraception were found to be at 0.9 to 1.9 times greater risk of a first-time diagnosis with depression, depending on which type of birth control pills, patches, rings, or hormonal intrauterine devices (IUDs) they used. And adolescent girls were found to be at 1.2 to 3.2 times greater risk, though the researchers noted this could be influenced by the fact that this age group is more vulnerable to general risk factors for depression.
“Both doctors and women should be aware of this potential side effect,” said Dr. Øjvind Lidegaard, the study’s senior author and a gynecologist at the University of Copenhagen. While he emphasized that the vast majority of women will not develop depression while on hormonal contraception, he said it’s arguable that at-risk women, especially adolescents, might want to consider alternatives like a copper IUD.
The research was published in JAMA Psychiatry and funded in part by the foundation that is the majority owner of the drug company Lundbeck, which sells antidepressants.
An incomplete picture
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.
Piecing the puzzle together
Lidegaard said he and his team are working on a similar study assessing whether there’s an association between taking hormonal birth control and attempting or committing suicide.
And experts are calling for more research that could flesh out the findings of the Danish study. “I hope that a study like this helps somebody get funding for the prospective study that’s really needed … comparing [hormonal contraception users] to condom and copper IUD users,” said Dr. Katharine O’Connell White, an OB/GYN at Boston University.
Researchers still don’t understand what effect, if any, hormonal contraception may have on depression risk. But they emphasize that even if a link exists, the baseline risk remains very small; the vast majority of women can and do use hormonal contraception without any mental health problems. Experts’ message for women: Don’t be afraid to use hormonal contraception.
“Often you have to take each study as a piece of the puzzle, and as we go along we get a better picture of what the puzzle is going to look like,” said Dr. Jennifer Gunter, a Bay Area OB/GYN. “I think it’s really important not to sound alarms based on individual puzzle pieces.”
This study I think gets at the underlying physiologic changes we are noticing in our patients on long term OCP’s. It has been our running theory of late for patients on OCP’s (a combination of estrogen and progesterone hormones) that many, maybe more than 50% are not getting enough estrogen effect. These women are acting as if their estrogen levels are closer to menopause than normal. Symptoms include but not limited to, Depression, anxiety, panic attacks, migraine headaches, memory problems, ADD, joint pain, night sweats, urinary frequency and urgency, vaginal dryness, decreased libido, oily skin, acne, hair loss etc. We almost routinely supplement estrogen for these women. All the symptoms go away with supplementation. We try to avoid oral estrogen because the pill is oral, so patch, cream, and vaginal delivery methods are available.
Michael D. Fox, MD
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