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

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 m 2 ) and a high body mass index (≥25 kg/m 2 ) 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.