The effect of very low calorie diet on liver morphology.
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Adult↗
Biomedical subjects
C Gluud
Publications and source records attributed to C Gluud.
Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females.
During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.
Adult↗
No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men.
The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction. Sexual dysfunction was significantly (p less than 0.05) associated with lower serum concentrations of testosterone, non-protein-bound testosterone, and non-sex hormone-binding globulin-bound testosterone. The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared, however, when age, ethanol consumption, and severity of liver disease were included as covariates in the analysis. During follow-up (median 30 mo, range 1-48 mo) sexual dysfunction improved significantly (p less than 0.05) at 6, 12, and 24 mo. Furthermore, the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period (p less than 0.01). However, the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function. In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients.
Clinical Trials as Topic↗
Thyroid hormones and thyroxine-binding globulin in relation to liver function and serum testosterone in men with alcoholic cirrhosis.
In 73 euthyroid male patients with histologically verified alcoholic cirrhosis, thyroid hormones, thyroxine-binding globulin (TBG) and testosterone concentrations (total, non-protein- and non-SHBG-bound) were studied in relation to each other and to the degree of liver dysfunction. Serum concentrations of triiodothyronine (T3) decreased significantly (p less than 0.05) and thyroid-stimulating hormone (TSH) increased with progressing liver dysfunction. Serum concentrations of tetraiodothyronine (T4), TBG and T4/TBG ratio did not correlate significantly with liver function. Serum T3 concentrations correlated significantly (Kendall Tau-beta = -0.33, p = 0.001) with total serum testosterone concentrations, while there was a negative correlation (Kendall Tau-beta = -0.20, p = 0.025) between testosterone and TSH values. No correlation was found between testosterone concentrations and serum levels of TBG. It is proposed that the association between T3 and TSH on one hand and testosterone concentrations on the other reflects a covariation of these variables with liver function. The TBG level was normal in most patients and was not correlated to testosterone concentrations.
Adult↗
Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases.
The aim of this study was to examine the serum concentrations of sex steroids and pituitary hormones in a randomly selected group of alcoholic cirrhotic men participating in a randomized, placebo-controlled study on the efficacy of oral testosterone treatment on the liver. Before treatment, patients (n = 25) had median serum concentrations of testosterone, oestradiol, non-protein bound oestradiol, non-sex hormone binding globulin (SHBG) bound oestradiol and oestrone sulphate which did not differ significantly from those of healthy controls (n = 16), but the patients had significantly (P less than 0.01) higher median serum concentrations of oestrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. The patients were randomized to treatment with either oral micronized testosterone (200 mg t.d.s.) or placebo for a median duration of 1 year. In the placebo group (n = 8), hormone concentrations at follow-up were not significantly different from those at entry apart from a significant (P less than 0.05) increase in FSH concentrations. Median concentrations of testosterone, oestrone, and oestrone sulphate increased significantly (P less than 0.05) in the testosterone-treated group (n = 17) when compared with concentrations at entry and concentrations in the placebo group. The testosterone-treated group had significantly (P less than 0.05) higher serum concentrations of non-protein bound and non-SHBG bound oestradiol when compared with concentrations at entry, but no significant changes were observed regarding serum oestradiol and prolactin concentrations. Both LH and FSH concentrations decreased significantly (P less than 0.05) in the testosterone-treated group when compared with concentrations at entry and concentrations in the placebo group.
Adult↗
The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men.
Seventy-three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined before entry and during follow-up. No significant differences were observed before entry or during follow-up between the two treatment groups. T3, T4 and T4/TBG ratio did not change significantly during follow-up, while TBG concentrations decreased (P less than 0.05). Using a multivariate test, it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function of sex hormone receptors in their liver.
Administration, Oral↗
Testosterone and alcoholic cirrhosis. Epidemiologic, pathophysiologic and therapeutic studies in men.
The present review summarizes the pathogenic mechanisms leading to variation of plasma testosterone concentrations, consequences of hypoandrogenization and hyperoestrogenization, and effects of oral testosterone treatment in men with alcoholic cirrhosis. These patients have normal median plasma testosterone concentrations, but 20% have values above and 20% have values below the normal limits. The majority of patients have raised sex hormone binding globulin (SHBG) concentrations. This increase accounts for the supranormal plasma testosterone concentrations. With decreasing liver function, plasma testosterone concentrations decrease significantly. The combination of increased SHBG levels and decreasing liver function leads to low or subnormal plasma concentrations of non-protein bound and non-SHBG bound testosterone. This decrease, together with raised oestrogen concentrations, may explain the increased prevalence of gynecomastia and testicular atrophy which raises with decreasing liver function. Oral testosterone treatment of alcoholic cirrhotic men produces an increase in the plasma concentrations of testosterone, androstenedione and dihydrotestosterone, but oestrogen concentrations increase as well. Oral testosterone treatment significantly reduces the prevalence of gynecomastia, but is without significant effects on liver biochemistry, morphology, haemodynamics, and function, general well being, sexual dysfunction and survival of alcoholic cirrhotic men. A pooled estimate of the mortality risk of cirrhotic patients treated with anabolic-androgenic steroids does not disclose any significant difference compared with placebo treatment (relative risk 0.98; 95% confidence limits 0.77-1.22). Seldom, but serious, side-effects of oral testosterone treatment can not be excluded.
Administration, Oral↗
Influence of ethanol on development of hyperplastic nodules in alcoholic men with micronodular cirrhosis.
The type of cirrhosis was blindly evaluated in follow-up liver biopsies performed on 106 alcoholic men with micronodular cirrhosis. The median time interval from entry to follow-up liver biopsy was 31 mo (range, 3-44 mo). Patients were stratified into four groups according to their maximal registered ethanol consumption during follow-up. Thirty-six patients (34%) abstained from ethanol, 40 patients (38%) consumed a small amount of ethanol (less than 50 g/day), 19 patients (18%) consumed a moderate amount of ethanol (51-100 g/day), and 11 patients (10%) consumed an excessive amount of ethanol (greater than 100 g/day) during follow-up. Follow-up liver biopsy specimens demonstrated micronodular cirrhosis in 54 patients (51%), micronodular cirrhosis with development of hyperplastic nodules in 47 patients (44%), and nonclassifiable macronodular cirrhosis in 4 patients (4%); 1 patient showed portal fibrosis. The cumulative prevalence of patients developing hyperplastic nodules increased significantly (p = 0.014 for trend) with decreasing ethanol consumption, the prevalence being 57% in abstainers, 58% in those who consumed a small amount of ethanol, 32% in those who consumed a moderate amount, and 18% in those who consumed an excessive amount. In conclusion, alcoholic men with micronodular cirrhosis develop hyperplastic nodules during follow-up, the rate and prevalence of which is significantly related to the amount of ethanol consumed during follow-up. Ethanol consumption may inhibit hepatocellular proliferation in alcoholic men with micronodular cirrhosis.
Adult↗
Serum testosterone concentrations in men with alcoholic cirrhosis: background for variation.
Median serum testosterone concentration of men with alcoholic cirrhosis (n = 216) did not differ significantly from normal controls (n = 51), but serum testosterone concentrations varied by a factor 43.9 in patients compared to 3.2 in controls (P less than .001). Nineteen percent of the patients had serum testosterone concentrations above 30 nmol/L. Serum concentrations of sex-hormone-binding globulin (SHBG) were significantly (P less than .001) raised, and serum concentrations of calculated nonprotein-bound and non-SHBG-bound testosterone were significantly (P less than .001) decreased in patients compared to normal control values. A number of background variables were analyzed with reference to serum testosterone concentrations by means of multiple regression techniques after having divided the patients into groups (A, B, C) with decreasing liver function by a modification of the Child-Turcotte's criteria. The only significant (P less than .01) background variables associated with log serum testosterone concentrations were: group C (beta = -0.828), group B (beta = -0.222), age (years) (beta = -0.012), duration of hospitalization (days) (beta = -0.0077), and concentration of SHBG (nmol/L) (beta = 0.0044). Neither previous nor recent (within last six months) alcohol consumption influenced serum testosterone concentrations significantly, but about 50% of the patients had abstained from ethanol for two months or more. The same background variables as above were included as significantly (P less than .01) associated with log serum concentrations of calculated nonprotein-bound testosterone and calculated non SHBG-bound testosterone, except that SHBG was insignificantly associated to any of the two proportions and that testicular volume was significantly (P less than .05) associated with log non-SHBG bound testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Humans↗
Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption.
Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patient group, a significant change in median values of portal pressure (-23%, n = 34, P less than 0.005), hepatic blood flow (-22%, n = 28, P less than 0.001), indocyanine green clearance (+16%, n = 29, P less than 0.01), and galactose elimination capacity (+8%, n = 31, P less than 0.05) was observed. However, testosterone-treated patients did not differ significantly from placebo-treated patients regarding any of the measured variables. No significant relationships could be demonstrated between ethanol consumption and liver haemodynamics and liver function, but the number of patients consuming more than 100 g ethanol per day decreased significantly (P less than 0.001) from 22 (65%) before entry to one (3%) during follow-up. In conclusion, oral testosterone treatment of men with alcoholic cirrhosis does not explain the significant improvement of liver haemodynamics and function observed in this study. However, the improvement may be due to reduced ethanol consumption.
Administration, Oral↗
Increased plasma fibronectin concentrations in obesity: normalization during weight loss.
In 23 morbidly obese patients we investigated the influence of a large weight loss (30.6 kg, range 17.5-90.8) on the plasma fibronectin concentrations. Further, changes in plasma fibronectin were related to serum insulin levels and to liver biochemistry. Between the measurements patients had been treated with an intermittent very-low-calorie formula diet sufficient in respect to protein, minerals and vitamins. They were investigated in weight-stable states. Before weight reduction, 14 patients (61%, 95% confidence limits 39-80%) had elevated plasma fibronectin levels. Plasma fibronectin decreased (medians 1.22 and 0.59 mumol/l before and after weight loss, p less than 0.01) and was after weight loss within the normal range in 14 patients. The change in plasma fibronectin was unassociated with the magnitude of the weight loss as well as with the reduction of overweight. The resulting plasma fibronectin levels were also uncorrelated with the body weight and with the final degree of overweight. Serum insulin decreased (p less than 0.01) during the weight reduction and the change correlated (p less than 0.05) with the change in plasma fibronectin. Serum lactate dehydrogenase, which is associated with the degree of hepatic fatty change, declined (p less than 0.01), but the individual change was unrelated with the change in plasma fibronectin. In conclusion, the elevated plasma fibronectin levels in morbidly obese subjects seem to normalize during weight loss. We suggest the normalization to be mediated--at least in part--by a reduction of the insulin levels.
Adult↗
Androgens and oestrogens before and following oral testosterone administration in male patients with and without alcoholic cirrhosis.
Compared with controls (N = 9), alcoholic cirrhotic men (N = 14) showed: significantly (P less than 0.05) higher serum concentrations of sexual hormone binding globulin (SHBG), androstenedione, oestrone, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol; significantly (P less than 0.05) lower concentrations of albumin and non-SHBG bound testosterone; no significant differences regarding concentrations of testosterone, dihydrotestosterone, non-protein bound testosterone, oestrone sulphate, and SHBG bound oestradiol. Following oral administration of 400 mg of micronized testosterone, serum concentrations of testosterone, dihydrotestosterone, androstenedione, and oestrone increased significantly (P less than 0.05) in both groups, cirrhotic patients reaching significantly (P less than 0.01) higher concentrations than controls. Further, in the cirrhotic group, the serum concentrations of oestrone sulphate, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol, and the urinary excretion of oestrogen increased significantly P less than 0.05). In conclusion, peroral testosterone administration decreases the serum oestradiol/testosterone ratio in patients with normal livers as well as in patients with alcoholic cirrhosis, but the latter group obtains significantly higher oestrogen concentrations.
Administration, Oral↗
Variables predicting elevated portal pressure in alcoholic liver disease. Results of a multivariate analysis.
In 46 alcoholic patients the association of wedged-to-free hepatic-vein pressure with other variables (clinical, histologic, hemodynamic, and liver function data) was studied by means of multiple regression analysis, taking the wedged-to-free hepatic-vein pressure as the dependent variable. Four variables showed significant independent association with the wedged-to-free hepatic-vein pressure: indocyanine green clearance (p = 0.031), degree of necrosis (p = 0.023), degree of hepatic architectural destruction (graded as: preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) (p = 2.3 X 10(-6) and sex (p = 0.0024), male sex being associated with higher wedged-to-free hepatic-vein pressure. The multiple coefficient of determination (R2) was 0.63; thus, 63% of the variation in the wedged-to-free hepatic-vein pressure was 'explained' by variation in these four variables.
Adult↗
No effect of long-term oral testosterone treatment on liver morphology in men with alcoholic cirrhosis.
The effect of oral testosterone treatment (200 mg tid) on liver morphology was examined in a double-blind, placebo controlled study including men with alcoholic cirrhosis (n = 126). Liver biopsies obtained before randomization showed micronodular cirrhosis in 119 patients (94%), alcoholic hepatitis in 64 (51%), and fatty liver in 104 (83%). These and other morphological findings did not differ significantly in the patients randomized to testosterone (n = 76) and to placebo (n = 50) (skewed randomization 3:2). Follow-up liver specimens (biopsies or autopsies) obtained after a median treatment duration of 30 months demonstrated a significant (p less than 0.01) increase in the prevalence of macronodular cirrhosis (from 6 to 51%) and a significant (p less than 0.01) decrease in the prevalence of alcoholic hepatitis (to 21%) and of fatty liver (to 52%). Testosterone treatment did not significantly influence the prevalence of these changes. Further, testosterone treatment had no significant effect on the prevalence of other morphological changes, including vascular and malignant changes. However, in the testosterone-treated group one patient developed diffuse sinusoidal dilation and one patient showed Budd-Chiari's syndrome. The degree of fatty liver and of alcoholic hepatitis in follow-up liver specimens were significantly (p less than 0.002) higher among patients who consumed ethanol during follow-up than in patients who abstained (76 versus 22% and 30 versus 6%). In conclusion, this study does not establish any indication or any contraindication in terms of hepatic histopathology with the possible exception of hepatic venous thrombosis for the use of oral testosterone treatment in men with alcoholic cirrhosis.
Biopsy↗
Widespread use of condoms and low prevalence of sexually transmitted diseases in Danish non-drug addict prostitutes.
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Adult↗
Sampling variability in percutaneous liver biopsy.
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Biopsy, Needle↗
Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics.
Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal no significant difference was found in androgen concentrations between the diabetic and the normal subjects. The normal diurnal profiles, with highest androgen concentrations in the morning before insulin withdrawal (08:00) and lowest concentrations at 20:00 h were maintained in the diabetics. However, testosterone and dihydrotestosterone concentrations were lower in the diabetics after 4 h of insulin withdrawal and remained so throughout the study. The concentrations of androstenedione were not significantly different between diabetics and normal subjects except after 4 h of insulin withdrawal. Despite the patients without B-cell function were more metabolically decompensated from after 4 h of insulin withdrawal compared with patients with B-cell function, no significant differences were found in androgen concentrations between the two groups although a tendency to lower concentrations were seen in the group without B-cell function.
Adolescent↗
The influence of insulin on the raised plasma fibronectin concentration in human obesity.
Plasma concentrations of fibronectin, free insulin, C-peptide and plasma glucose were determined in 40 morbidly obese subjects and in 51 normal weight controls, matched for sex and age. All plasma concentrations were significantly elevated (p less than 0.01) among the obese subjects. A significant correlation (r = 0.34, p less than 0.05) between plasma fibronectin and plasma free insulin was found among the obese patients, but not among the controls (r = -0.02, p greater than 0.05). No significant correlation was found between plasma fibronectin and plasma C-peptide, neither in the obese patients nor in the controls (obese r = 0.06, controls r = 0.02; p greater than 0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r = 0.21, controls r = 0.15; p greater than 0.05) and percentage overweight (obese r = 0.27, controls r = 0.04; p greater than 0.05). The raised level of circulating insulin may in part explain the excess of plasma fibronectin obese subjects.
Adult↗