Depression Linked to Hormonal Contraceptives

Megan Brooks

September 29, 2016

Women who use oral hormonal contraceptives are at increased risk of developing depression, and adolescents seem most vulnerable, results of a large study suggest.

"Women should generally be informed about this potential side effect with use of hormonal contraception, so they can react appropriately in case of mood changes or even depression development. Likewise, doctors who prescribe hormonal contraception should be aware of this potential risk," Øjvind Lidegaard, MD, Department of Gynecology, Rigshospitalet, Copenhagen, and Faculty of Health Sciences, University of Copenhagen, told Medscape Medical News.

The study was published online September 28 in JAMA Psychiatry.

Mood Changes

Mood changes are a known reason for stopping hormonal contraceptives, but few studies have quantified the effect of low-dose hormonal contraception on the risk for depression, the researchers note.

To investigate, they used Danish registry data for more than 1 million women and adolescents (aged 15 to 34 years) with no prior history of depression or other psychiatric diagnosis at baseline. The women were followed from 2000 through 2013; the average follow-up was 6.4 years.

During follow-up, 55.5% of participants were current or recent users of hormonal contraception. There were 133,178 first prescriptions for antidepressants and 23,077 first diagnoses of depression.

During follow-up, compared with nonusers, women and adolescents who used hormonal contraception were more likely to be prescribed an antidepressant for the first time. The risk varied by type of hormonal contraception.

Table. Risk for First Use of Antidepressant by Hormonal Contraception

Type of Contraception Relative Risk 95% CI
Combined oral contraceptive pills 1.2 1.22 - 1.25
Progestin-only pills 1.3 1.27 - 1.40
Patch (norgestrolmin) 2.0 1.76 - 2.18
Vaginal ring (etonogestrel) 1.6 1.55 - 1.69
Levonorgestrel intrauterine system 1.4 1.31 - 1.42

95% CI, 95% confidence interval.


The relative risks for a first diagnosis of depression were similar or slightly lower, the investigators report.

They also found that after 6 months of starting hormonal contraceptives, the relative risk peaked at 1.4 (95% CI, 1.34 - 1.46) for first use of antidepressants and 1.5 (95% CI, 1.36 - 1.64) for diagnosis of depression.

In age-stratified analyses, the relative risks for first antidepressant use generally decreased with increasing age.

Patients aged 15 to 19 years seem most vulnerable to mood changes. In this group, the relative risk for first use of an antidepressant was 1.8 (95% CI, 1.75 - 1.84) with combined oral contraceptives and 2.2 (95% CI, 1.99 - 2.52) with progestin-only pills. For adolescents using nonoral birth control products, the risk for first use of an antidepressant was threefold higher than for nonusers.

"Noteworthy" Research

Dr Lidegaard told Medscape Medical News, "This is the first study ever conducted which has followed a large cohort of previously mentally healthy women starting on hormonal contraception...and then followed these women for 13 years for their eventual start on antidepressant therapy or getting a depression diagnosis, as compared with age-matched women not starting on hormonal contraception. At the same time, the study controls for important potential confounders. Women with previous mental disease were excluded, as were pregnant women."

The findings support the theory of progesterone involvement in the etiology of depression, because progestin dominates combined and progestin-only contraceptives, the investigators say.

Reached for comment, Keely Cheslack-Postava, PhD, associate research scientist, Department of Psychiatry, Columbia University Medical Center in New York City, described the study as "thorough and well-conducted, making use of nationwide registry data.

"The study is noteworthy for its careful attention to the relationship in timing between use of hormonal contraceptives vs depression diagnosis or treatment.

"On the other hand, it should be noted that previous studies do present conflicting evidence about the relationship between hormonal contraception and women's mental health. One aspect that needs further study is the distinction between diagnosed depression vs depressive symptoms that may or may not come to medical attention," she added.

The study was supported by the Department of Gynecology, Rigshospitalet, University of Copenhagen, and by a grant from the Lundbeck Foundation. Dr Lidegaard has received received honoraria for talks on pharmacoepidemiologic issues within the past 3 years from Exeltis.

JAMA Psychiatry. Published online September 28, 2016. Abstract


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