Hormonal Contraception-Associated Depressive Episodes May Be Linked to PPD Risk

Depression associated with hormonal contraception (HC) use may indicate susceptibility to postpartum depression (PPD), linking depressive episodes with hormonal contributions, findings published in JAMA Psychiatry suggest.

Conducted in Denmark, the population-based cohort study aimed to investigate the association between depressive episodes and HC use in women during their reproductive years. Using health care data from national registers, the study included all women in Denmark born after 1978 who delivered their first child between January 1, 1996, and June 30, 2017. Women were excluded if they had never used HC, had immigrated or emigrated, had a depressive episode before 1996 or within 12 months before delivery, or had multiple births or stillbirths.

Researchers calculated crude and adjusted odds ratios (ORs) for the incidence of PPD, defined as “filling a prescription for antidepressant medication or obtaining a hospital discharge diagnosis of depression within 6 months after first childbirth.” A depressive episode was defined as filling a prescription of antidepressant medication or obtaining a depression discharge diagnosis from a psychiatric clinic.  

Of the included 188,648 first-time mothers, 2457 (1.3%) developed PPD, 5722 (3%) had a history of HC-associated depression, 18431 (9.8%) had a history of non-HC-associated depression, and 164,495 (87.2%) had no history of depression.

“Notably, women with HC-associated depression had more depressive episodes than women with non-HC-associated depression, with 63.4% vs 38.6% having had more than 1 episode, respectively,” researchers said.

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Women with a history of depression associated with HC initiation had a higher risk of developing PPD compared to women with a history of depression not associated with HC initiation, the study found. The risk of PPD was also lower for women with no previous depression compared to women with non-HC-associated depression.

“Our findings contribute new evidence for an association between depressive episodes across hormonal transitions in the reproductive life span, supporting the existence of a hormone-sensitive subgroup of women,” researchers wrote in the study. “Our findings also align with previous findings suggesting an association between PPD and the retrospective reporting of experienced mood deterioration associated with HC use.”

Study authors noted a few limitations, including the use of antidepressant prescriptions as a proxy for depression, which may introduce misclassification bias. Further, the study cannot establish a causal relationship between HC use and PPD, and unmeasured confounders and other factors may also influence the results.

“This work contributes evidence to guide clinical PPD risk stratification and potentially improve PPD prediction models,” the authors concluded. “Future work should evaluate risk models for PPD that include information on previous depressive episodes and subclinical depressive symptoms associated with HC use, which could potentially further inform a stratified approach to reproductive care.”

Reference

Larsen SV, Mikkelsen AP, Lidegaard Ø, Frokjaer VG. Depression associated with hormonal contraceptive use as a risk indicator for postpartum depression. JAMA Psychiatry. 2023;80(7):682–689.