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| PMID |
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| TITLE |
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| Poor mood after oral contraceptive use is associated with increased vulnerability to peripartum depression, premenstrual dysphoric disorder, and higher genetic risk for depression. |
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| ABSTRACT |
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| PURPOSE |
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| 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 |
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| 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. 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 |
|
| 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. 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). 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 ; PMDD: RR = 3.78,CI=[2.4-6.0], P = 2.2 × 10 ; prior depression: RR = 1.32,CI=[1.1-1.5], P = 5.9 × 10 ; child/teen depression onset: RR = 1.56,CI=[1.3-1.8], P = 1.1 × 10 ). 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 ), 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 ); no prior or child/teen depression onset: RR = 1.27,CI=[1.1-1.4], P = 3.1 × 10 . |
| CONCLUSIONS |
|
| 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. 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). 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 ; PMDD: RR = 3.78,CI=[2.4-6.0], P = 2.2 × 10 ; prior depression: RR = 1.32,CI=[1.1-1.5], P = 5.9 × 10 ; child/teen depression onset: RR = 1.56,CI=[1.3-1.8], P = 1.1 × 10 ). 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 ), 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 ); no prior or child/teen depression onset: RR = 1.27,CI=[1.1-1.4], P = 3.1 × 10 . 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. |
| © 2026. The Author(s). |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2025/07/10 |
| accepted |
2026/04/29 |
| medline |
2026/05/06 12:36 |
| pubmed |
2026/05/06 12:35 |
| entrez |
2026/05/06 11:17 |
| pmc-release |
2026/05/06 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Kiewa J |
|
Kiewa |
Jacqueline |
J |
|
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. j.kiewa@uq.edu.au. |
| Lind PA |
|
Lind |
Penelope A |
PA |
|
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. |
| Hickie IB |
|
Hickie |
Ian B |
IB |
|
Brain and Mind Centre, The University of Sydney, Sydney, Australia. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. |
| Mitchell BE |
|
Mitchell |
Brittany E |
BE |
|
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. |
| Middeldorp CM |
|
Middeldorp |
Christel M |
CM |
|
Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, Netherlands. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
Department of Psychiatry, University of Oxford, Oxford, UK. |
| Byrne EM |
|
Byrne |
Enda M |
EM |
|
Child Health Research Centre, University of Queensland, Brisbane, Australia. enda.byrne@uq.edu.au. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 29 |
| ISSUE: 3 |
| TITLE: Archives of women's mental health |
| ISOABBREVIATION: Arch Womens Ment Health |
| YEAR: 2026 |
| MONTH: May |
| DAY: 06 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1435-1102 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Arch Womens Ment Health |
| COUNTRY: Austria |
| ISSNLINKING: 1434-1816 |
| NLMUNIQUEID: 9815663 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Depression |
| Genetics |
| Mood effects |
| Oral Contraceptive Pill |
| Reproductive depression |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Humans |
|
| Female |
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| Contraceptives, Oral |
adverse effects |
| Premenstrual Dysphoric Disorder |
chemically induced |
| Adult |
chemically induced |
| Peripartum Period |
psychology |
| Depression |
psychology |
| Australia |
epidemiology |
| Genetic Predisposition to Disease |
epidemiology |
| Affect |
drug effects |
| Genetic Risk Score |
drug effects |
| Middle Aged |
drug effects |
| Risk Factors |
drug effects |
| Major Depressive Disorder |
genetics |
| Perimenopause |
psychology |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Contraceptives, Oral |
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| OTHER ID's |
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