Accumulation of 5 alpha-reduced androgen glucosiduronates associated with impaired removal in young male hemodialysis patients.

Abstract

Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients. Even though an improvement in general status and well-being has been noted after recombinant human erythropoietin supplementation, no significant changes were observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha-reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol and androsterone) profiles were studied in 23 young male stable dialyzed patients and compared to an age-matched group of healthy subjects. 5 alpha-Reduced androgen glucosiduronates are products of peripheral testosterone (T) metabolism and seem to be a useful tool in assessment of the male androgen status. Their polarity facilitates their urinary excretion, and their clearance is similar to the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig cell dysfunction supported by normal serum estradiol and T levels, low free T, and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA) sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA sulfate levels remained in the normal range; 3) an accumulation of 5 alpha-reduced androgen glucosiduronates, whose removal was impaired as shown by their very low sieving coefficients (< 0.012). Taken together, the above observations are consistent with alteration of spermatogenesis with respect to dialysis duration in which earlier elevated baseline serum LH levels indicate a primary defect in Leydig cell function.

Gonadal function in men with chronic illness

“…Others have found normal or reduced oestradiol levels but elevated LH and FSH values, suggesting there is an effect of uraemia at the testicular level, impairing testosterone synthesis. (Mastrogiacomo et al, 1988, Boudou et al, 1995 Spermatogenesis is impaired in patients with uraemia and those receiving haemodialysis; improving with renal transplantation. Testicular biopsies show sperm maturation is affected, and there may be complete germinal aplasia (Holdsworth et al, 1977).…”