Hypothalamo-Pituitary Gonadal Axis in Chronic Renal Failure

Chronic renal failure causes extensive neuroendocrine disturbance, including marked hypothalamo-pituitary dysfunction which is reversed by renal transplantation but not dialysis. Gonadal dysfunction in uremia is manifest as delayed puberty in adolescents; as testicular atrophy, hypospermatogenesis, infertility, impotence in men; and as anovulation, infertility, and menstrual disturbance in women. Gonadal steroidogenesis and gametogenesis are impaired and gonadotropin levels are increased. In addition to evidence of defects in pituitary and gonadal function, increasing evidence indicates the importance of alterations in hypothalamic regulation of pituitary-gonadal function in the pathogenesis of uremic hypogonadism. Experimental uremia induced by subtotal nephrectomy in mature rats causes gonadal dysfunction, which is principally due to aberrant neuroendocrine regulation of GnRH secretion involving inhibition of GnRH secretion, hypersensitivity to negative testicular feedback, and resistance to naloxone, a triad of features termed ontogenic regression.