Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS

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dc.contributor.authorHouston, Emma J.
dc.contributor.authorTempleman, Nicole M.
dc.date.accessioned2026-05-07T17:31:18Z
dc.date.available2026-05-07T17:31:18Z
dc.date.issued2025
dc.description.abstractPolycystic ovary syndrome (PCOS), a reproductive endocrine disorder with quintessential features of metabolic dysfunction, affects millions of women worldwide. Hyperinsulinemia (i.e., elevated insulin without hypoglycemia) is a common metabolic feature of PCOS that worsens its reproductive symptoms by exacerbating pituitary hormone imbalances and increasing levels of bioactive androgens. Hyperinsulinemia in PCOS is often attributed to insulin resistance, based on the concept that impaired insulin-mediated glucose disposal would induce compensatory insulin hypersecretion. However, it is challenging to define the sequential relationship between insulin sensitivity and insulin secretion, as they are tightly interlinked, and evidence suggests that hyperinsulinemia can alternatively precede insulin resistance. Notably, other drivers of hyperinsulinemia (outside of insulin resistance) may be highly relevant in the context of PCOS. For instance, high androgen levels can augment both hyperinsulinemia and insulin resistance, generating a self-perpetuating cycle of reproductive and metabolic dysfunction. In this review, we evaluate the cause-and-effect relationships between insulin resistance and hyperinsulinemia in PCOS. We examine evidence for the prevailing theory of insulin resistance as the primary defect that causes secondary compensatory hyperinsulinemia, and an alternative framework of hyperinsulinemia as the earlier defect that perpetuates reproductive and metabolic features of PCOS. Considering the heterogeneous nature of PCOS, it is improbable that its metabolic characteristics always follow the same progression. Comprehensively examining all mechanistic regulators of hyperinsulinemia and insulin resistance in PCOS might thereby lead to improved prevention and management strategies, and address critical knowledge gaps in the progression of PCOS pathogenesis.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipResearch in the Templeman laboratory is supported by funding from the Canadian Institutes of Health Research (PJT-183618), the Natural Sciences Engineering Research Council of Canada (RGPIN-2022-05149) and the Women’s Health Research Institute. EJH received a Canada Graduate Scholarship from the Canadian Institutes of Health Research and a British Columbia Graduate Scholarship. NMT is a Tier 2 Canada Research Chair in Cell Biology, a Michael Smith Health Research BC Scholar and a member of the Sexual and Reproductive Health and Rights Research Cluster at the University of Victoria.
dc.identifier.citationHouston, E. J., & Templeman, N. M. (2025). Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS. Journal of Endocrinology, 265(2), e240269. https://doi.org/10.1530/JOE-24-0269
dc.identifier.urihttps://doi.org/10.1530/JOE-24-0269
dc.identifier.urihttps://hdl.handle.net/1828/23842
dc.language.isoen
dc.publisherJournal of Endocrinology
dc.rightsCC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSexual and Reproductive Health and Rights (SRHR) Aspiration Research Cluster
dc.subjectpolycystic ovary syndrome
dc.subjectinsulin
dc.subjectandrogens
dc.subjectmetabolic dysfunction
dc.subjectinsulin hypersecretion
dc.subjectinsulin clearance
dc.subjectinsulin sensitivity
dc.subject.departmentDepartment of Biology
dc.titleReappraising the relationship between hyperinsulinemia and insulin resistance in PCOS
dc.typeArticle

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