Objective: Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol-induced liver disease. We have evaluated hypothalamic-pituitary-testicular function in patients with end-stage non-alcoholic liver disease before and at 6 and 12 months after hepatic transplantation.
Design: A prospective study of hypothalamic-pituitary-testicular endocrine function before and after cadaveric hepatic transplantation.
Patients: Fifty four consecutive patients with end-stage, non-alcoholic liver disease were evaluated before and after liver transplantation.
Measurements: Hypothalamic-pituitary-testicular (HPT) axis function was evaluated under basal conditions by single morning measurements of plasma total and free testosterone, sex hormone-binding globulin and by plasma LH and FSH responses to 100 micrograms i.v. GnRH.
Results: Men with chronic non-alcoholic liver disease had reduced levels of total and free testosterone and increased levels of SHBG compared with controls with normal liver function. Total and free testosterone were positively correlated with basal and stimulated LH (but not FSH) concentrations. Gonadotrophin responses to GnRH were preserved but delayed compared with healthy controls consistent with a predominantly hypothalamic defect in regulation of pituitary-testicular function. Increasing severity of underlying liver disease was associated with declining total and free testosterone as well as peak GnRH-stimulated LH concentrations. Spironolactone treatment was associated with decreased circulating testosterone levels only in men with liver disease of intermediate severity (Child-Pugh class B). Following hepatic transplantation, total and free testosterone and SHBG concentrations returned progressively towards eugonadal control levels over the first 12 months but total and free testosterone levels remained subnormal.
Conclusions: Hypothalamic-pituitary regulation of testicular function is impaired in end-stage non-alcoholic liver disease in proportion to the severity of underlying liver disease. Spironolactone reduces circulating testosterone but only among men with Child-Pugh B liver cirrhosis. Gonadal function improves, but is not normalized, over the first year following successful liver transplantation.