The influence of ethanol and liver disease on sex hormones and hepatic oestrogen receptors in women

Abstract

In contrast to the numerous studies of men, very few studies have been concerned with sex hormone disturbances in women with chronic alcoholic and non-alcoholic liver diseases. The aim of the study was, to evaluate the effect of ethanol and liver dysfunction on menstrual cycle, serum sex hormone concentrations and hepatic oestrogen receptors in women. In premenopausal female alcoholics ethanol consumption increase the frequency of menstrual disturbances, abortions, and miscarriages, while infertility is not frequent. Acute ethanol intoxication has only minor effects on pituitary-gonadal hormones in premenopausal women, while chronic ethanol abuse lead to reduced concentrations of sulphated steroids, and these changes may be seen before severe liver dysfunction has appeared. In women liver dysfunction lead to earlier occurrence of menopause in comparison with normal controls, while information is insufficient or lacking regarding the influence upon fertility, pregnancy outcome and sexual behavior in women. In postmenopausal women with alcoholic and non-alcoholic liver disease, the main disturbances of sex hormone metabolism consist of elevated oestrone and sex hormone binding globulin (SHBG) concentrations, while serum concentrations of steroid sulphates and 5 alpha-dihydrotestosterone (DHT) are reduced, and the degree of liver dysfunction is a major determinant for the observed disturbances. The presence of high affinity, low capacity, specific oestrogen receptors (ER) in the liver is confirmed using a ligand binding assay (DCC), specificity analyses, and sucrose gradient centrifugation. Furthermore, the sensitivity of an enzyme immunoassay has been improved enabling the quantitative measurement of hepatic ER in 102 small liver biopsies from patients with alcoholic and non-alcoholic liver diseases. The method is suitable for quantitative assessment and ER in small tissue samples, and can be applied to other tissues than the liver. Patients with chronic liver diseases have significantly lower hepatic ER concentrations, and this reduction is determined by the degree of liver dysfunction, while the degree of alcoholic hepatitis or active ethanol consumption are less important factors. The importance of this observation for hepatic physiology and pathophysiology remains to be determined.