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Postpartum hormonal contraceptive use and risk of depression

Larsen, S. V.; Ozenne, B.; Mikkelsen, A. P.; Liu, X.; Madsen, K. B.; Munk-Olsen, T.; Lidegaard, O.; Frokjaer, V. G.

2024-10-02 epidemiology
10.1101/2024.09.27.24314424 medRxiv
Show abstract

ImportanceHormonal contraceptive (HC) use is associated with depression. It is, however, unknown whether this is also true in the postpartum period where women have a heightened depression risk and are routinely offered to start HC. ObjectiveTo determine if HC initiation postpartum is associated with depression development within 12 months postpartum. DesignA cohort study based on Danish register data. SettingNationwide population-based. ParticipantsAll primiparous women in Denmark who gave birth from 1997 through 2022. Women were excluded if they had a depression within 24 months prior to delivery, had multiple birth or stillbirth, or a diagnosis of breast cancer or liver tumor. ExposureHC initiation within 12 months postpartum treated as a time-varying exposure. HC types were categorized as combined oral contraceptives (COCs), combined non-oral contraceptives (CNOCs), progestogen-only pills (POPs), and progestogen-only non-oral contraceptives (PNOCs). Main Outcome and MeasureDepression defined as filling an antidepressant prescription or receiving a hospital depression diagnosis. Adjusted hazards ratios (HRs) and average absolute risks of depression within 12 months postpartum were estimated using Cox regression and a G-formula estimator. ResultsOf 610,038 first-time mothers, 41% initiated HC within 12 months postpartum (mean [SD] age; 27.6 [4.3] years for HC users vs. 29.6 [4.8] years for non-users). HC initiation was associated with subsequent depression with a HR of 1.49 (95% CI, 1.42;1.56) compared to no use resulting in an increase in the 12-month absolute risk from 1.36% (1.32;1.39) to 1.54% (1.50;1.57).The HR for COC was 1.72 (1.63;1.82); CNOC 1.97 (1.64;2.36); PNOC 1.40 (1.25;1.56). POP exposure was associated with an initially reduced instantaneous risk but it was increased late postpartum. Investigating the impact of timing of initiation showed that the earlier COC was initiated postpartum the higher the associated rate ratio of depression. Conclusions and RelevanceHC initiation postpartum was associated with 49% higher instantaneous depression risk resulting in an increase in 12-month risk from 1.36% to 1.54% in the observed population. Such associated risk was higher the earlier it was initiated postpartum, at least for COC. This raises the question if depression incidence postpartum is inflated by routine HC initiation after childbirth.

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