Men with chronic liver disease frequently develop clinical signs of hypogonadism and overt feminisation. Associated with these features, they have been found to have a reduced production of testosterone with low plasma concentrations, but only a minority of cirrhotic men would seem to have a marginal increase in circulating biologically potent oestrogens. Furthermore, this latter finding does not correlate with the presence of clinical feminisation. The original hypothesis to explain these changes now seems less likely to be true and no other single hypothesis has, on its own, been found to provide an adequate explanation for all the clinical and biochemical features found in cirrhotic men. It may be that the pathogenesis of endocrine changes in cirrhotic men is multifactorial--for instance, a combination of decreased hepatic clearance of some oestrogenic compounds, an autoimmune mediated primary testicular defect, and a specific potentiation effect by alcohol. Alternatively, it may be that none of these suggested mechanisms is of importance and that the endocrine changes are mediated instead by other mechanisms which remain, as yet, undiscovered or unconsidered. The fascination which this problem has held for clinicians and biochemists for many years seems likely to persist for some time to come.
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