Effect of a single administration of ketoconazole on total and physiologically free plasma testosterone and 17β-oestradiol levels in healthy male volunteers

Summary The effect of a single oral dose of 400 mg ketoconazole, given as an 80 mg/ml suspension, on total and physiologically free (i.e. non-sex hormonebound) testosterone and 17-oestradiol has been investigated in 6 healthy male volunteers. The two steroids fell to nadir levels of 18 and 60% of their respective initial concentrations 6 hours after drug intake, and then completely recovered. Although in vitro slight displacement of testosterone from the sex-hormone binding globulin, by high doses of ketoconazole was found, the physiologically free concentration of testosterone in vivo was closely correlated with that of the total hormone, suggesting that there is no direct interference with sex-hormone binding globulin in vivo. Plasma LH and FSH were not significantly modified by treatment. The effect of ketoconazole on plasma oestradiol levels was less pronounced and was not clearly related to a block of the aromatase system, as reported in vitro.This work was presented in part at the International Symposium on the Regulation of Androgen Actions, Montreal, 29th June–1st July 1984     

Some comments on the use of statistics in the evaluation of drug trials in migraine

Statistical aspects need particular attention in reporting on drug studies in migraine. It is important to report on all patient and disease characteristics which have contributed to the diagnosis and on all variables used for the evaluation of the result; the use of median values, accompanied by the extremes, is recommended in this context. Comparability of the study groups should be examined and possibly repeated after exclusion of the defaulters, if their number is substantial. As regards the presentation of the results, it does not suffice to give p values only: the magnitude of the response should be given and the use of techniques estimating the reliability of this magnitude (e.g. confidence intervals) and/or its reproducibility (e.g. power calculations) is recommended. An analysis of three unrelated groups of migraineurs demonstrates that most pertinent variables show a non-Gaussian distribution, and this includes the distribution of treatment results. For this reason, the use of nonparametric tests is advocated.