Changes in the SHBG concentration during danazol treatment

Serum levels of sex hormone binding globulin (SHBG) were measured by radioelectro-immunoassay before and during administration of danazol in daily doses varying between 200 and 800 mg for a period of 1-6 months. The patients consisted of different groups of regularly menstruating women (n = 76) and of postmenopausal women (n = 12). A rapid proportional decrease in SHBG was seen at all dose levels in both pre- and postmenopausal women, starting within the first 24 hours and reaching statistical significance by 48 hours. The fractional rate of fall appeared to be determined by the metabolic half-life of the protein itself. Plotting log concentrations of SHBG versus time and using the slope of the linear regression for calculations, the half-life of SHBG appeared to be 15 +/- 5.7 (SD) days. After approximately one month of treatment, the SHBG concentrations began to approach a new steady state at a level of approximately 20-30% of the original concentration, depending on the dose of danazol. The proportional suppression of SHBG was significantly greater following 600 or 800 mg of danazol daily than following 200 or 400 mg. However, with all doses the SHBG levels after one month of treatment were well below the levels normally found in healthy males. The mean proportional reduction following a certain dose was almost identical in premenopausal and postmenopausal women. The findings of the present investigation suggest that danazol exerts a direct inhibitory effect on the hepatic synthesis of SHBG, which is dependent of the dose of danazol, independent of estrogen concentration, but possibly accentuated by endogenous androgens.