Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin

Abstract

Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.

PIP: The effect of fluoxymesterone (9 alpha-fluoro-11 beta, 17 beta-dihydroxy-17 alpha-methyl-4-androstene-3-one) on the pituitary-gonadal axis and the role of testosterone-estradiol-binding globulin (TeBG) were investigated. 4 normal men and 2 agonadal men were given fluoxymesterone for 3 days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and luteinizing hormone (LH) were measured every 30 minutes on a control day and on the 1st day of treatment. T and LH were measured every 6 hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes/day decreased from 10.5 to 6.2 (p less than .01), mean 24-hour LH decreased from 12.6 mIU/ml to 9.3 mIU/ml (p less than .01), and mean 17-OHP decreased from 2.33 ng/ml to 1.18 ng/ml (p less than .01) in all normal subjects. T decreased from 464.5 ng/100 ml to 294.2 ng/100 ml (p less than .01). By the 3rd day of treatment, LH had decreased further in 4 and T in 3 of 4 normals. Mean LH levels and the number of LH spikes did not decrease in the agonadal patients. Fluoxymesterone displaced T in vitro from plasma binding proteins with an apparent equilibrium constant of 1 X 10(8) and 1.9 X 10(7) in female and male plasma, respectively, at 22 degrees C and 5.2 X 10(7) and 8 X 10(6) at 37 degrees C. In polyacrylamide gel electrophoresis a 500-fold more excess of fluoxymesterone decreased the peak of TeBG-bound T significantly (p less than .01, 45%). These in Vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vitro.