This cohort study found associations between hormonal contraceptives and depression risk among first-time moms in the first year postpartum.
Researchers found that initiating hormonal contraception postpartum was associated with an "instantaneous" higher risk of depression.
However, one outside expert was not convinced the results have clinical significance.
Among first-time mothers in Denmark, initiating hormonal contraception postpartum was associated with an "instantaneous" higher risk of depression, a population-based cohort study found.
Compared to no use, hormonal contraceptive initiation was associated with subsequent depression (adjusted HR 1.49, 95% CI 1.42-1.56), and the absolute risk of depression at 12 months postpartum rose from 1.36% to 1.54%, reported Vibe Gedsø Frøkjaer, PhD, of Copenhagen University Hospital-Rigshospitalet in Denmark, and colleagues.
Adjusted hazard ratios varied slightly by type of hormonal contraception, with combined oral contraceptives at 1.72, progestogen-only non-oral contraceptives at 1.40, and combined non-oral contraceptives at 1.97. Progestogen-only pill exposure "was associated with an instantaneously reduced risk in the early study period, but it was increased late postpartum," authors wrote in JAMA Network Open.
"These findings raise the issue of whether the incidence of depression postpartum may be inflated by routine [hormonal contraceptive] initiation, which is important information to convey at postpartum contraceptive counseling," the authors wrote.
Initiation of hormonal contraceptives has been associated with an increased risk of depression, but it is unclear whether this also applies in the postpartum period when women are already at a greater risk of developing depression. In the U.S., postpartum depression rates have risen in recent years.
Authors found that when combined oral contraceptives were initiated earlier in the postpartum period, there were higher rate ratios of associated depression.
However, Nikki Zite, MD, MPH, from the University of Tennessee Graduate School of Medicine in Knoxville, said that this study "does not definitively tell us that hormonal contraception causes more postpartum depression."
Although the results were statistically significant, Zite is not convinced they are clinically significant. She pointed out that the population reported a lower rate of depression than expected.
The authors didn't look at how many encounters patients had within the healthcare system or use a validated tool to diagnose depression, Zite noted, which she said "could lead to an over-association among those that were engaged in care and therefore more likely to have a contraceptive prescribed."
"While I am happy people are investigating postpartum depression, I am unsure this report adds valuable information and actually may create an undeserved fear of hormonal contraception," Zite said.
This population-based cohort study used Danish register data from all primiparous women who gave birth between January 1997 and December 2022. Depression within 24 months before delivery, multiple births, stillbirths, and diagnosis of breast cancer or liver tumor were exclusion criteria. Hormonal contraception initiation within 12 months postpartum was the main exposure.
There were 610,038 first-time mothers included. Forty-eight patients died within 12 months of delivery and 3,287 were lost to follow up.
In total, 40.7% of first-time mothers initiated hormonal contraception within 12 months postpartum, of whom 23.6% initiated combined oral contraceptives, 10.9% progestogen-only pills, 5.3% progestogen-only non-oral contraceptives, and 0.9% combined non-oral contraceptives. Mean follow-up exposure time for hormonal contraception was 7.7 months. About half of women who started progestogen-only pills filled their prescription between 7 and 10 weeks postpartum.
The primary outcome was depression -- defined as filling an antidepressant prescription or receiving a hospital diagnosis -- within 12 months postpartum. Mean maternal age was 27.6 for users and 29.6 for nonusers. Authors didn't find conclusive patterns of heightened risk based on age.
Within 12 months of delivery, 1.5% of women developed depression. The crude incidence rate of depression was 21 per 1,000 person-years for mothers exposed to hormonal contraception and 14 per 1,000 person-years for non-exposed mothers.
Authors noted several limitations, including the study's observational nature, that depression is not always why people take antidepressants, that when a prescription was filled may not be when it was initiated, and the findings may not apply to milder cases of depression. Plus, the findings may have healthy user bias and some women may not start hormonal contraception due to previous adverse experiences.
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Rachael Robertson is a writer on the MedPage Today enterprise and investigative team, also covering OB/GYN news. Her print, data, and audio stories have appeared in Everyday Health, Gizmodo, the Bronx Times, and multiple podcasts. Follow
Disclosures
The study was funded by The Independent Research Fund Denmark.
Frøkjaer reported receiving lecture fees from Lundbeck Pharma, Janssen-Cilag, Gedeon-Richter, and Ferring.
Co-authors reported relationships with Medice Nordic, Lundbeck, and Exeltis.
Zite had no disclosures.
Primary Source
JAMA Network Open
Source Reference: Larsen SV, et al "Postpartum hormonal contraceptive use and risk of depression" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2025.2474.