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. 2025 Mar;8(2):e70030.
doi: 10.1002/edm2.70030.

Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits

Raymond N C Chan  1 , Chuiguo Huang  1 , Noel Y H Ng  1 , Henry C H Tam  1 , Claudia H T Tam  1 , Feifei Cheng  1 , Kwun Kiu Wong  1 , Mai Shi  1 , Alex C W Ng  1 , Atta Y T Tsang  1 , Chi Chiu Wang  2   3 , Lai Ping Cheung  2 , Wing Hung Tam  2 , Mugdha V Joglekar  4 , Anandwardhan A Hardikar  4 , Alicia J Jenkins  1   5   6 , Juliana C N Chan  1   3   7   8 , Cadmon K P Lim  1   3 , Ronald C W Ma  1   3   7   8
Affiliations

Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits

Raymond N C Chan et al. Endocrinol Diabetes Metab. 2025 Mar.

Abstract

Background: Polycystic ovary syndrome (PCOS) is one of the commonest gyneco-endocrine disorders amongst women of reproductive age. Whether PCOS and cardiometabolic traits in PCOS patients are associated with shortened telomere length (TL) or relative leukocyte telomere length (rLTL) remains unclear.

Methods: 214 women with PCOS and 214 age-matched women were recruited. rLTL was measured with an updated quantitative real-time PCR protocol and reported as ΔΔCt between telomere and a single-copy gene encoding β-globin relative to a normalisation control. A two-way Mendelian randomization analysis using the UK Biobank Resource was performed to assess the causal relationship between rLTL and PCOS.

Results: Women with PCOS had significantly shortened rLTL (PCOS: 0.5 ± 0.7; control: 0.8 ± 0.6; p < 0.001). Longer rLTL was associated with a lower risk of PCOS after adjusting for age, history of smoking and other cardiometabolic traits (OR: 0.503; 95% CI: 0.342-0.730; p < 0.001). Longer rLTL was associated with reduced risk of dyslidpidemia (OR: 0.563; 95% CI: 0.450-0.968; p = 0.042) in PCOS patients. PCOS subjects with rLTL shorter than mean of the rLTL of control subjects had an elevated risk of dysglycemia (OR: 2.09; 95% CI: 1.04-4.29; p = 0.040). No causal relationships were found between rLTL and PCOS in the Mendelian randomization study.

Conclusions: Women with PCOS have significantly reduced rLTL and shorter LTL may be associated with cardiometabolic risk factors in PCOS subjects. There are no causal relationship between genetically determined PCOS and TL or vice versa.

Keywords: dysglycemia; dyslipidemia; leukocyte telomere length; polycystic ovary syndrome.

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Conflict of interest statement

J.C.N.C. received consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Celltrion, MSD, Pfizer, Servier and Viatris Pharmaceutical, speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, MSD, Merck, Sanofi and Servier and research grants through her institutions from Applied Therapeutics, Astra Zeneca, Hua Medicine, Lee Powder, Lilly, Merck and Servier. R.C.W.M. has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi, Tricida Inc. and honoraria for consultancy or lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Merck and Roche Diagnostics, all used to support diabetes research at the Chinese University of Hong Kong. J.C.N.C., C.K.P.L. and R.C.W.M. are co‐founders of GemVCare, a technology start‐up initiated with support from the Hong Kong Government Innovation and Technology Commission and its Technology Start‐up Support Scheme for Universities (TSSSU). A.J.J. has received research grants for clinical trials from Abbott and Sanofi‐Aventis, and honoraria for consultancy for Abbott, Amgen, Medtronic and Sanofi‐Aventis. No other potential conflicts of interest relevant to this article were reported.

Figures

FIGURE 1
FIGURE 1
Mediation analysis showing dysglycemia and dyslipidemia partially mediated the association between polycystic ovary syndrome (PCOS) and relative leukocyte telomere length (rLTL). Data can be referred to Table S9.
See this image and copyright information in PMC

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