Context The classical interpretation of the feedback regulation of the male hypothalamo–pituitary–gonadal axis predicts that a partial inhibition of testosterone (T) synthesis will result in a compensatory rise in LH secretion. The question arises as to whether such a compensation is complete or that decreased T synthesis may result in a lower plasma T concentration.
Objective To investigate whether a moderate inhibition of T synthesis capacity will be fully compensated by increased LH secretion.
Design, subjects and interventions In nine young healthy men, we partially inhibited T synthesis capacity using ketoconazole (KTZ) 100 mg four times daily. On day –6 (1 week prior to KTZ intake), days 1 and 8 of KTZ administration blood was drawn [07:00 h (t1), 10:00 h (t2), 13:00 h (t3)] for evaluation of T, LH, oestradiol (E2), 17‐OH‐progesterone (17OHP), progesterone (PR) and sex hormone binding globulin (SHBG). On day 8, 5000 IU of hCG were administered to evaluate the maximal T secretion under KTZ.
Results Administration of KTZ resulted in an acute, moderate but significant decrease of plasma T concentration. On day 8, plasma LH, 17OHP and PR were elevated relative to day –6 and day 1, but mean T was still lower compared to day –6. Mean E2 and SHBG were only slightly affected by KTZ. After stimulation by hCG, plasma T was restored to its baseline level.
Conclusion These results argue against the assumption that a moderate decline in T synthesis capacity will be compensated completely by increased LH secretion.