SAT-262 Sex-Specific Effects of Statins on Cholesterol and Steroid Metabolism in Dyslipidemia: Implications for Androgen Biosynthesis

Abstract Disclosure: J. Noh: None. H. Seo: None. H. Oh: None. H. Seo: None. M. Choi: None. Statins inhibit hepatic cholesterol biosynthesis and affect steroidogenesis, with previous studies indicating reduced serum levels of testosterone, particularly in men. However, the extent of statin-induced alterations in cholesterol and steroid metabolism across sexes remains unclear. This study aimed to evaluate sex-specific sterol and steroid profiles influenced by statins in individuals with dyslipidemia. Gas chromatography-mass spectrometry was performed to quantify twelve sterols and sixteen steroids in serum samples from a dyslipidemia cohort, consisting of 321 men and 349 women aged 41–80. Statins exerted a more pronounced effect on sterol profiles in men (p < 1×10⁻¹³ for all) compared to women (p < 1×10⁻⁶ for all). The metabolic ratio of pregnenolone to cholesterol, a marker of CYP11A1 activity, was significantly reduced in men (p < 0.001), alongside a decrease in the testosterone/androstenedione ratio, reflecting diminished testosterone biosynthesis (p < 0.04). In contrast, no significant changes were observed in testosterone levels or related metabolic ratios in women (p > 0.4 for all). Reductions in cholesterol precursors, such as lanosterol, lathosterol, desmosterol, and 7-dehydrocholesterol, further suggest that statins exert a stronger inhibitory effect on cholesterol metabolism in men than in women. These findings underscore sex-specific metabolic effects of statins, particularly their impact on reduced androgen biosynthesis in men. Presentation: Saturday, July 12, 2025