Association between female reproductive factors and gout: a nationwide population-based cohort study of 1 million postmenopausal women

Yeonghee Eun,Dong Wook Shin,Jaejoon Lee,Dong-Yun Lee,Kyu Na Lee,Eun-Mi Koh,Hyungjin Kim,Seonyoung Kang,In-Young Kim,Kyungdo Han,Seulkee Lee,Hoon-Suk Cha

doi:10.1186/s13075-021-02701-w

Abstract

BackgroundPrevious studies have shown that the incidence and risk factors of gout differs according to sex. However, little research has been done on the association between reproductive factors and gout. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout.MethodsA total of 1,076,378 postmenopausal women aged 40–69 years who participated in national health screenings in 2009 were included in the study. The outcome was the occurrence of incident gout, which was defined using the ICD-10 code of gout (M10) in the claim database. Cox proportional hazard models were used for the analyses and stratified analyses according to body mass index (BMI) and the presence/absence of chronic kidney disease (CKD) were performed.ResultsThe mean follow-up duration was 8.1 years, and incident cases of gout were 64,052 (incidence rate 7.31 per 1000 person-years). Later menarche, earlier menopause, and a shorter reproductive span were associated with a high risk of gout. No association between parity and gout incidence was observed. Use of oral contraceptives (OC) and hormone replacement therapy (HRT) were associated with an increased risk of gout. The association between reproductive factors and gout was not statistical significant in the high BMI group. The effects of OC and HRT usage on gout were not significant in the CKD group.ConclusionShorter exposure to endogenous estrogen was associated with a high risk of gout. Conversely, exposure to exogenous estrogen such as OC and HRT was associated with an increased risk of gout.

Highlights

Gout is the most common inflammatory arthritis in adults, and its incidence has constantly increased over recent decades [1]
In a study published in 2008 that had analyzed data from the US National Health and Nutrition Examination Survey (NHANES) from 1988 to 1994, it had been reported that menopause was associated with higher serum uric acid levels, while hormone replacement therapy (HRT) was associated with lower uric acid levels [8]
The differences were not significant, subjects diagnosed with gout had late menarche, early menopause, and short reproductive span, and had higher rates of use of oral contraceptive (OC), HRT, and breastfeeding for ≥1 year compared to subjects without gout

Summary

Introduction

Gout is the most common inflammatory arthritis in adults, and its incidence has constantly increased over recent decades [1]. A cross-sectional analysis of 1530 women had shown that postmenopausal status, earlier age at menarche, and history of oral contraceptive (OC) use were associated with high serum uric acid concentration [5]. In the Nurses’ Health Study, early menopause was associated with an increased risk of incident gout, and hormone replacement therapy (HRT) was associated with a decreased risk of gout [7]. In a study published in 2008 that had analyzed data from the US National Health and Nutrition Examination Survey (NHANES) from 1988 to 1994, it had been reported that menopause was associated with higher serum uric acid levels, while HRT was associated with lower uric acid levels [8]. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout

Methods

Results

Discussion

Conclusion