The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men

Abstract

ABSTRACT— 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<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.

Testosterone stimulates extra‐hepatic but not hepatic fat oxidation (Fox): comparison of oral and transdermal testosterone administration in hypopituitary men

“…Oral testosterone was prepared by Fresh Therapeutics (Sydney, Australia) as capsules filled with crystalline testosterone USP without excipients. The dose of oral testosterone was based on known pharmacokinetics 9–11,13,14 and designed to increase portal but not peripheral blood testosterone concentrations with an androgenic effect on hepatic function as indicated by effects on SHBG and TBG 15–17 . Because of the absence of prior data as to what dose of oral testosterone induces a pharmacological effect, we used a dose finding study which committed us to a stepwise sequential design.…”

“…The dose of oral testosterone was based on known pharmacokinetics [9][10][11]13,14 and designed to increase portal but not peripheral blood testosterone concentrations with an androgenic effect on hepatic function as indicated by effects on SHBG and TBG. [15][16][17] Because of the absence of prior data as to what dose of oral testosterone induces a pharmacological effect, we used a dose finding study which committed us to a stepwise sequential design. Previous studies have indicated that oral testosterone doses in excess of 200 mg/day are required to increase testosterone levels in peripheral blood.…”

Serum testosterone levels and testosterone supplementation in cirrhosis: A systematic review

“…Becker et al allocated 45 patients with alcoholic cirrhosis to oral T vs 28 patients to placebo. They found a significant increase in median serum T levels at 36 months in the treatment group compared to the placebo group (548 ng/dl in both groups at entry; 1327 vs 606 ng/dl at 1 month; 1356 vs 721 ng/dl at 6 months; and 1327 vs 865 ng/dl at 36 months, P < .01) 19 . After 14 patients with alcoholic cirrhosis and nine healthy controls with similar median baseline T levels were treated with 400 mg of oral T, serum T increased in both groups at 48 hours compared to baseline but reached higher levels in the cirrhosis than the control group ( P < .05) 22 .…”

“…They found a significant increase in median serum T levels at 36 months in the treatment group compared to the placebo group (548 ng/dl in both groups at entry; 1327 vs 606 ng/dl at 1 month; 1356 vs 721 ng/dl at 6 months; and 1327 vs 865 ng/dl at 36 months, P < .01). 19 After 14 patients with alcoholic cirrhosis and nine healthy controls with similar median baseline T levels were treated with 400 mg of oral T, serum T increased in both groups at 48 hours compared to baseline but reached higher levels in the cirrhosis than the control group (P < .05). 22 Likewise, in a study of 25 patients with alcoholic cirrhosis, oral T supplementation led to an increase in serum T after a median duration of 1 year, while there was no difference between pre-and post-treatment T levels in the placebo group (P < .02).…”

Abnormal thyroid test results in euthyroid state: An appraisal of the role of drugs

“…This could be due to inadequate expression of sex hormone receptors in the liver, increase in serum estrogen concentration and use of antiandrogenic medication like spironolactone. 64 Short term studies have suggested a possible shift of T4 binding from TBG to transthyretin during therapy with norethandrolone due to lower TBG levels. 65 From a clinical perspective, androgen therapy may unmask or worsen mild hyperthyroidism due to reduction of TBG levels.…”