MON-626 - Impaired Testosterone Biosynthesis in Diabetic Men Is Independent of Statin Use

This study aimed to investigate whether statin-induced cholesterol lowering affects steroidogenesis, with a particular focus on testosterone biosynthesis in patients with diabetes. A cross-sectional analysis was conducted with 321 men and 349 women, aged 41 ~ 80 years, who underwent cardiovascular evaluation between March 2016 to February 2020. Participants were classified into four groups based on the presence or absence of diabetes and statin therapy status. Fasting serum samples were analyzed for quantitative profiles of sterols, steroids, and their metabolic ratios using gas chromatography-mass spectrometry. Concentrations were expressed as cholesterol (μg/mL) and other sterols or steroids (ng/mL). Based on serum levels of cholesterol and its precursors, including lathosterol, lanosterol, and desmosterol, statin-induced cholesterol-lowering was more pronounced in men (p < 1 × 10⁻¹³ for all) than in women (p < 1 × 10⁻⁶ for all). However, this reduction was significantly blunted, by more than twofold, in individuals with diabetes, regardless of sex. Overall, statin use was associated with significantly lower serum testosterone levels in men (3.86 ± 1.71 vs. 4.26 ± 1.98 ng/mL, p < 0.05). When stratified by diabetes status, this association was not statistically remarkable between statin users and non-users within the diabetic group (3.54 ± 1.74 vs. 3.99 ± 1.36 ng/mL, p = 0.114) or non-diabetic group (4.04 ± 1.68 vs. 4.30 ± 2.06 ng/mL, p = 0.404). Diabetic men showed significantly lower levels of dehydroepiandrosterone (DHEA, p < 0.009) and testosterone (p < 0.05), along with a decreased testosterone-to-androstenedione ratio (p < 0.02) and an increased androstenedione-to-DHEA ratio (p < 0.002), suggesting impaired testosterone biosynthesis independent of statin use. Statin-induced cholesterol-lowering effects were attenuated in the presence of diabetes, regardless of sex. Reduced testosterone biosynthesis was observed exclusively in men with diabetes, independent of statin use.

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