Longitudinal Changes in Serum Urate Levels from Pre-menopause through Post-menopause: Interrupted Time-Series Analyses.

Abstract

OBJECTIVES Hyperuricemia (HU) and gout are common in post-menopausal women. We aimed to identify the longitudinal changes in serum urate (SU) levels during and after the menopausal transition and its interaction with coexisting SU-modifying conditions. METHODS This longitudinal study included Japanese women who underwent annual medical examinations from April 2004 to September 2024 and had at least one visit before and after self-reported menopause. Menopausal transition stages were categorized into pre-menopause, peri-menopause (5 years prior to and up to the menopause), and post-menopause. Longitudinal changes in SU and HU (SU ≥6.8 mg/dL or taking medications for gout/HU) were examined by interrupted time-series analyses and evaluated across stratified subgroups. RESULTS We analyzed 8,169 eligible participants with 93,511 visits over a median follow-up of 13.8 years. SU levels gradually increased during pre-menopause, rose sharply over peri-menopause, and stabilized in post-menopause. Compared to pre-menopause, the mean SU level was 0.41 mg/dL (95% CI: 0.38, 0.43) higher in post-menopause. HU prevalence increased from <1.0% during pre-menopause to 4-5% during post-menopause. Compared to pre-menopause, the associations of a low estimated glomerular filtration rate (<60 mL/min/1.73 m2) and a high body mass index (≥25 kg/m2) with HU were greater in post-menopause; HU was observed in approximately 18% of overweight or obese women at menopause. CONCLUSIONS SU levels rapidly increase during peri-menopause and are already elevated by the time of menopause. Maintaining a normal body weight and preserving kidney function prior to menopause may decrease postmenopausal HU and potentially prevent subsequent gout in women.