Obesity, Circulating Androgens and their Precursors

Objective: The association of obesity with a lower circulating testosterone level in men is well documented. However, reports on possible changes in the androgen spectrum in obesity are rare. Methods: To investigate this phenomenon, serum sex hormone-binding globulin (SHBG), testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and its sulphate, 17α-hydroxypregnenolone, 17α-hydroxyprogesterone and gonadotrophins LH and FSH concentrations were measured in fasting blood samples of 224 men divided into three groups - normal (BMI=18-25, n=109, overweight (BMI 25.10-30, n=78) and obese (BMI=30.1-39, n=37). Results: A significant decrease in testosterone, dihydrotestosterone, 17α-hydroxypregnenolone, 17α-hydroxyprogesterone and SHBG with increasing body mass index was observed, whereas insignificant changes for dehydroepiandrosterone and its sulphate, androstenedione and gonadotrophins LH and FSH, were found. The ratios of corresponding pairs of steroids were in agreement with the concept that in obesity splitting of the side chain of C 21 -steroids, and 17β-hydroxysteroid dehydrogenase-reducing activity are decreased. No changes for steroid 5α-reductase or 3β-hydroxysteroid dehydrogenase (HSD3B2) were found. Conclusion: The findings demonstrate that, in men with increasing body mass index, the formation of C 19 steroids decreases from their C21 precursors and lower 17β-hydroxysteroid dehydrogenase further confines the production of testosterone and dihydrotestosterone.