Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome

Alex E Henney; Conor S Gillespiec; Jonathan Y M Lai; Pieta Schofield; David R Riley; Rishi Caleyachetty; Thomas M Barber; Alexander D Miras; Laurence J Dobbie; David M Hughes; Uazman Alam; Theresa J Hydes; Daniel J Cuthbertson

doi:10.1210/clinem/dgae481

Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome

Alex E Henney, Conor S Gillespiec, Jonathan Y M Lai, Pieta Schofield, David R Riley, Rishi Caleyachetty, Thomas M Barber, Alexander D Miras, Laurence J Dobbie, David M Hughes, Uazman Alam, Theresa J Hydes, Daniel J Cuthbertson

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Background

Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype.

Methods

Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes.

Results

We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01).

Conclusion

Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

Original language	English
Pages (from-to)	1235-1246
Number of pages	12
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	110
Issue number	5
Early online date	11 Jul 2024
DOIs	https://doi.org/10.1210/clinem/dgae481
Publication status	Published (in print/issue) - 22 Apr 2025

Data Access Statement

The data that support the findings of this study are available
from the UK Biobank (https://www.ukbiobank.ac.uk/).

Keywords

polycystic ovary syndrome
type 2 diabetes
metabolic dysfunction-associated steatotic liver disease
cardiovascular disease
hormone-dependent cancers

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1210/clinem/dgae481Licence: CC BY

dgae481Final published version, 666 KBLicence: CC BY

Cite this

Henney, A. E., Gillespiec, C. S., Lai, J. Y. M., Schofield, P., Riley, D. R., Caleyachetty, R., Barber, T. M., Miras, A. D., Dobbie, L. J., Hughes, D. M., Alam, U., Hydes, T. J., & Cuthbertson, D. J. (2025). Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism, 110(5), 1235-1246. https://doi.org/10.1210/clinem/dgae481

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title = "Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome",

abstract = "BackgroundPolycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype.MethodsUsing UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes.ResultsWe included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01).ConclusionCardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.",

keywords = "polycystic ovary syndrome, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, cardiovascular disease, hormone-dependent cancers",

author = "Henney, {Alex E} and Gillespiec, {Conor S} and Lai, {Jonathan Y M} and Pieta Schofield and Riley, {David R} and Rishi Caleyachetty and Barber, {Thomas M} and Miras, {Alexander D} and Dobbie, {Laurence J} and Hughes, {David M} and Uazman Alam and Hydes, {Theresa J} and Cuthbertson, {Daniel J}",

year = "2025",

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day = "22",

doi = "10.1210/clinem/dgae481",

language = "English",

volume = "110",

pages = "1235--1246",

journal = "The Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "5",

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Henney, AE, Gillespiec, CS, Lai, JYM, Schofield, P, Riley, DR, Caleyachetty, R, Barber, TM, Miras, AD, Dobbie, LJ, Hughes, DM, Alam, U, Hydes, TJ & Cuthbertson, DJ 2025, 'Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome', The Journal of Clinical Endocrinology & Metabolism, vol. 110, no. 5, pp. 1235-1246. https://doi.org/10.1210/clinem/dgae481

TY - JOUR

T1 - Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome

AU - Henney, Alex E

AU - Gillespiec, Conor S

AU - Lai, Jonathan Y M

AU - Schofield, Pieta

AU - Riley, David R

AU - Caleyachetty, Rishi

AU - Barber, Thomas M

AU - Miras, Alexander D

AU - Dobbie, Laurence J

AU - Hughes, David M

AU - Alam, Uazman

AU - Hydes, Theresa J

AU - Cuthbertson, Daniel J

PY - 2025/4/22

Y1 - 2025/4/22

N2 - BackgroundPolycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype.MethodsUsing UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes.ResultsWe included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01).ConclusionCardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

AB - BackgroundPolycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype.MethodsUsing UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes.ResultsWe included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01).ConclusionCardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

KW - polycystic ovary syndrome

KW - type 2 diabetes

KW - metabolic dysfunction-associated steatotic liver disease

KW - cardiovascular disease

KW - hormone-dependent cancers

UR - https://academic.oup.com/jcem/article/110/5/1235/7710690

U2 - 10.1210/clinem/dgae481

DO - 10.1210/clinem/dgae481

M3 - Article

C2 - 38986027

SN - 0021-972X

VL - 110

SP - 1235

EP - 1246

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 5

ER -

Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome

Abstract

Data Access Statement

Keywords

UN SDGs

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