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• There were differential effects in different testosterone active states in gout. • Higher total testosterone in males linked to lower gout risk, not in females. • Higher free testosterone and bioavailable testosterone, higher risks of gout in males. • Higher SHBG were associated with lower risks of gout both in males and females. • Females have the lowest risk of gout at around 70 nmol/L SHBG levels. To investigate the associations between sex hormones and gout. A total of 448,836 individuals free of gout at baseline were included from the UK Biobank. Cox regression models were used to estimate hazard ratios (HRs) for gout. Besides, we investigated the causal relationship between bioavailable testosterone (BAT) and gout using mendelian randomization (MR). There were differential effects in different testosterone active states in gout. One-unit higher log-transformed total testosterone (TT) was associated with a 52 % [95 % CI, 0.39–0.58] lower risk of gout in males. In contrast, free testosterone (FT) and BAT were associated with a 74 % [95 % CI, 1.38–2.20] and a 78 % [95 % CI, 1.41–2.25] higher risk of gout in males respectively. For MR, the weighted median [OR, 1.70; 95 % CI, 1.14–2.56;] and inverse variance-weighted [OR, 1.25; 95 % CI, 0.96–1.62; P = 0.09] method revealed significant and approximately significant positive effect of genetic liability to BAT levels on the risk of gout respectively. Sex hormones were potentially associated with gout. Notably, we were the first to explore different testosterone states on gout and found that FT and BAT may increase the risk of gout in males, which is opposite to TT. And the former are active states of androgens, may be more accurately reflect the association between androgens and gout. [ABSTRACT FROM AUTHOR]