Poor mood after oral contraceptive use is associated with increased vulnerability to peripartum depression, premenstrual dysphoric disorder, and higher genetic risk for depression

Journal article

Purpose: This study tested whether adverse mood effect of the oral contraceptive pill (OCP) is associated with reproductive depressive episodes, including peripartum depression (PPD), premenstrual dysphoric disorder (PMDD), and perimenopausal depression. Method: In a sample of 3,547 OCP users from the Australian Genetics of Depression Study, who reported a lifetime depression diagnosis, logistic regression was used to test the association of PPD, PMDD, and perimenopausal depression with OCP adverse mood effect. Polygenic scores (PGS) for major depression (MD) were also tested for association with adverse mood effect. Sensitivity analyses tested for modification of these associations by a history of depression prior to first OCP use (prior depression), or by depression onset before the age of twenty (child/teen depression onset). Results: Adverse mood effect was reported by 1,342 OCP users (38%). PPD, PMDD, prior depression and child/teen depression onset were significantly associated with adverse mood effect (PPD: Relative Risk (RR) = 1.66,CI=[1.4–2.0], P = 2.0 × 10− 6; PMDD: RR = 3.78,CI=[2.4-6.0], P = 2.2 × 10− 8; prior depression: RR = 1.32,CI=[1.1–1.5], P = 5.9 × 10− 4; child/teen depression onset: RR = 1.56,CI=[1.3–1.8], P = 1.1 × 10− 7). The association of PPD with adverse mood effect remained significant for women with no prior or child/teen depression onset (RR = 1.77,CI=[1.3–2.4], P = 4.6 × 10− 4), but was not significant for women with both prior and child/teen depression onset. Adverse mood effect was significantly associated with PGS for MD: full sample: RR = 1.18,CI=[1.1–1.3], P = 3.6 × 10− 5); no prior or child/teen depression onset: RR = 1.27,CI=[1.1–1.4], P = 3.1 × 10− 4. Conclusions: Participants who experience an adverse mood effect with OCP use are likely to have higher genetic vulnerability for depression, and experience child/teen depression onset, as well as reproductive depressive episodes such as PPD.

Authors: Kiewa, J; Lind, PA; Hickie, IB; Medland, SE; Mitchell, BE

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Archives of Women's Mental Health
• Volume: 29
• Issue: 3
• Article number: 71
• Publication date: 2026-05-06
• Acceptance date: 2026-04-29
• DOI: 10.1007/s00737-026-01708-z
• EISSN: 1435-1102
• ISSN: 1434-1816
• Language: English
• Keywords: Oral Contraceptive Pill; Mood effects; Depression; Reproductive depression; Genetics