Journal Article Annotations
2025, 2nd Quarter

Women’s Mental Health

Annotations by Diana Punko, MD, MS
July, 2025

Postpartum Hormonal Contraceptive Use and Risk of Depression.

PUBLICATION #1 — Women’s Mental Health

Postpartum Hormonal Contraceptive Use and Risk of Depression.

Søren Vinther Larsen, Brice Ozenne, Anders Pretzmann Mikkelsen, Xiaoqin Liu, Kathrine Bang Madsen, Trine Munk-Olsen, Øjvind Lidegaard, Vibe Gedsø Frokjaer.

Abstract: JAMA Netw Open. 2025 Mar 3;8(3):e252474. doi: 10.1001/jamanetworkopen.2025.2474.

Importance:
Hormonal contraceptive (HC) use is associated with depression. It is, however, unknown whether this is also true in the postpartum period when women have a heightened depression risk and are routinely offered HC treatment.

Objective:
To examine whether HC initiation post partum is associated with the development of depression within 12 months post partum.

Design, setting, and participants:
A population-based cohort study based on nationwide Danish register data was conducted including all primiparous women who gave birth from January 1, 1997, through December 31, 2022. Women were excluded if they had depression within 24 months before delivery, multiple births or stillbirth, or a diagnosis of breast cancer or liver tumor. Data analysis was conducted between March 20, 2023, and January 17, 2025.

Exposure:
Hormonal contraceptive initiation within 12 months post partum was treated as a time-varying exposure. Hormonal contraceptive types were categorized as combined oral contraceptives (COCs), combined nonoral contraceptives (CNOCs), progestogen-only pills (POPs), and progestogen-only nonoral contraceptives (PNOCs).

Main outcomes and measures:
Depression within 12 months post partum, defined as filling an antidepressant prescription or receiving a hospital diagnosis of depression, was the main outcome. Adjusted hazard ratios (AHRs) and average absolute risks of depression within 12 months post partum were estimated using Cox proportional hazards regression and a G-formula estimator.

Results:
Of 610 038 first-time mothers, 248 274 (40.7%) initiated HCs within 12 months post partum (mean [SD] age, 27.6 [4.3] years for HC users vs 29.6 [4.8] years for nonusers). Hormonal contraceptive initiation was associated with subsequent depression, with an AHR of 1.49 (95% CI, 1.42-1.56) compared with no use, resulting in an increase in the 12-month absolute risk from 1.36% (95% CI, 1.32%-1.39%) to 1.54% (95% CI, 1.50%-1.57%). The AHR for COC was 1.72 (95% CI, 1.63-1.82); CNOC, 1.97 (95% CI, 1.64-2.36); and PNOC, 1.40 (95% CI, 1.25-1.56). Progestogen-only pill exposure was associated with an instantaneously reduced risk in the early study period, but it was increased late post partum. The earlier COCs were initiated post partum the higher the associated rate ratio of depression.

Conclusions and relevance:
In this cohort study, HC initiation post partum was associated with an instantaneous increased risk of developing depression. The associated risk was higher the earlier it was initiated post partum, at least for COC. This finding raises the issue of whether the incidence of depression post partum is increased by routine HC initiation after childbirth.

Annotation

The finding:
Initiation of hormonal contraceptive (HC) after delivery was associated with a 1.49 times increased risk for depression in the first year postpartum compared with no HC exposure. The risk was more pronounced for women without a prior history of mental disorder. The earlier combined oral contraceptive use was initiated post-partum, the higher the associated ratio of depression.

Strength and weaknesses:
Strengths of this study include the large sample size (610,038) and robust adjustment for confounders (including but not limited to age, calendar year, educational level, marital status, medical indications for HC use, in vitro fertilization treatment, and pregnancy and delivery complications). Limitations include its observational design (precluding causal inference), relatively homogenous population limiting generalizability (as data came from a Danish nationwide register), and assignment of depression outcome variable based on antidepressant medication fill or billing code rather than diagnostic clinical interview.

Relevance:
Given the elevated risk of depression in the postpartum period and the additional risk conferred by postpartum HC initiation, individualized risk assessment is essential. Women with a history of mood sensitivity to hormonal changes, prior perinatal depression, or other established risk factors should receive careful counseling regarding postpartum contraceptive choices. A nonhormonal alternative form of contraception may be preferred to prevent unintended pregnancy to mitigate the risk for postpartum depression.