The Role of Distress-related Metabolic Dysfunction in Ovarian Cancer Development: a pooled case-control study

Abstract

BackgroundEvidence suggests chronic distress influences ovarian cancer (OC) etiology and metabolomic profiles. Here, we evaluated the association of a metabolite-based distress score (MDS) and OC risk.

MethodsWe included two matched case-control studies nested within the Nurses Health Studies (N=584) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N=348). Metabolites were measured 3-27 years before diagnosis using liquid-chromatography tandem mass spectrometry. We examined the association of quintiles of MDS and 19 constituent metabolites with OC risk using unconditional logistic regression and stratified by tumor histotype, menopausal status, and age at diagnosis.

ResultsWe observed women in the highest versus lowest quintile of MDS had an increased OC risk (OR=1.62,95%CI=1.03-2.54,ptrend=0.07), and type 2 tumors (OR=1.71,95%CI=1.03-2.83,ptrend=0.11). Associations were suggestively stronger for premenopausal and <69-year-old women, and driven by pseudouridine, and N2,N2- dimethylguanosine.

ConclusionOur findings suggest chronic distress-associated metabolic dysregulation may represent a novel OC risk factor, especially among younger women.

A proposed psychometabolic endotype of polyendocrine metabolic ovarian syndrome: bidirectional interplay between psychological distress, eating dysfunction, sleep disruption, chronic stress, and metabolic deterioration.
Hongtao Li, Tong Yin, Yichen Wang +4
Frontiers in endocrinology7 Oct 2026Peer-reviewedCC BYFull textObstetrics, gynaecology & paediatricsEurope PMCCrossref
Associations of hirsutism and sexual function with mental health–related quality of life in women with polyendocrine metabolic ovarian syndrome
Müjde Canday, Aslıhan Yurtkal, Tural Ismayilov
Scientific Reports9 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textObstetrics, gynaecology & paediatricsCrossref
Inflammation-Related Biomarkers Linking Environmental Chemical Mixtures and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Population-Based Study from NHANES 1999-2020
T. Guo, Y. Zhao, S. Wang +2
medRxiv6 Oct 2026PreprintAll rights reservedFull textEpidemiology & public healthmedRxiv
Bulk and single-cell multiomics insights into theca cell and granulosa cell dysfunction in polyendocrine metabolic ovarian syndrome
Supraja M. Kodanch, Vaishnavi Vyas, Saumya Bansal +5
Journal of Ovarian Research7 Aug 2026Peer-reviewedCC BY 4.0Full textObstetrics, gynaecology & paediatricsPMC
Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets
Qiucheng Jia, Shuli Zhang, Lixin Zhang +3
Frontiers in Immunology7 Oct 2026Peer-reviewedCC BY 4.0Full textObstetrics, gynaecology & paediatricsCrossrefEurope PMC

Cite

BibTeX RIS

BibTeX

@misc{lin2026role,
  title = {{The Role of Distress-related Metabolic Dysfunction in Ovarian Cancer Development: a pooled case-control study}},
  author = {N. Lin and R. Balasubramanian and G. Menichetti and H. Eliassen and B. Trabert and J. Avila-Pacheco and M. K. Townsend and K. L. Terry and C. B. Clish and S. S. Tworoger and O. A. Zeleznik},
  howpublished = {medRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.27.26361473},
  url = {https://www.medrxiv.org/content/10.64898/2026.08.27.26361473v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - The Role of Distress-related Metabolic Dysfunction in Ovarian Cancer Development: a pooled case-control study
AU  - N. Lin
AU  - R. Balasubramanian
AU  - G. Menichetti
AU  - H. Eliassen
AU  - B. Trabert
AU  - J. Avila-Pacheco
AU  - M. K. Townsend
AU  - K. L. Terry
AU  - C. B. Clish
AU  - S. S. Tworoger
AU  - O. A. Zeleznik
PY  - 2026
DA  - 2026/08/27
PB  - medRxiv
DO  - 10.64898/2026.08.27.26361473
UR  - https://www.medrxiv.org/content/10.64898/2026.08.27.26361473v1
AB  - BackgroundEvidence suggests chronic distress influences ovarian cancer (OC) etiology and metabolomic profiles. Here, we evaluated the association of a metabolite-based distress score (MDS) and OC risk.  MethodsWe included two matched case-control studies nested within the Nurses Health Studies (N=584) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N=348). Metabolites were measured 3-27 years before diagnosis using liquid-chromatography tandem mass spectrometry. We examined the association of quintiles of MDS and 19 constituent metabolites with OC risk using unconditional logistic regression and stratified by tumor histotype, menopausal status, and age at diagnosis.  ResultsWe observed women in the highest versus lowest quintile of MDS had an increased OC risk (OR=1.62,95%CI=1.03-2.54,ptrend=0.07), and type 2 tumors (OR=1.71,95%CI=1.03-2.83,ptrend=0.11). Associations were suggestively stronger for premenopausal and <69-year-old women, and driven by pseudouridine, and N2,N2- dimethylguanosine.  ConclusionOur findings suggest chronic distress-associated metabolic dysregulation may represent a novel OC risk factor, especially among younger women.
ER  -

Abstract

Related

Cite