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Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study

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posted on 15.10.2021, 22:37 by Balachandran Kumarendran, Michael W O'Reilly, Anuradhaa Subramanian, Dana Šumilo, Konstantinos Toulis, Krishna M Gokhale, Chandrika N Wijeratne, Arri Coomarasamy, Abd A Tahrani, Laurent Azoulay, Wiebke Arlt, Krishnarajah Nirantharakumar
Objectives: Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptives (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (pre-diabetes and type 2 diabetes) in women with PCOS.

Research Design and Methods: Utilizing a large UK primary care database (The Health Improvement Network, THIN; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS, 123,545 matched controls), as well as a nested pharmaco-epidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2407 women with PCOS with [=cases] and without [=controls] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio and conditional logistic regression was used to obtain adjusted odds ratios (aORs).

Results: The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, p<0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59 to 0.87).

Conclusions: In this study limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow to exclude the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered to further understand these observations and potential causality.


This work has been supported by the Wellcome Trust (Investigator Grant WT209492/Z/17/Z, to WA) and the Health Research Board (Emerging Clinician Scientist Award ECSA-FA-2020-001, to MWOR). K.N. is a UK Research and Innovation (UKRI)/Health Data Research (HDR) UK Innovation Clinical Fellow. WA receives support from the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009). The views expressed are those of the authors and not necessarily those of the NIHR UK or the Department of Health and Social Care UK.