DEXAMETHASONE-INDUCED SUPPRESSION OF THE CIRCADIAN-RHYTHM OF PLASMA TESTOSTERONE IN NORMAL ADULT MALES

The aim of the present study was to investigate the dexamethasone-induced interference with the circadian rhythm of plasma testosterone. Normal adult males were treated with dexamethasone (3 mg/6 h) for 24 or 48 h or with a combination of dexamethasone and fluoxymesterone for 48 h. Following suppression of the nocturnal rise in testosterone by administration of dexamethasone, testosterone did not resume a circadian rhythm from day 2 to 3 under continued treatment, while plasma LH increased to about twice the baseline level. When the increase in LH was prevented by administration of fluoxymesterone (1.5mg at 6h intervals from 2200h on day 1 to 0400h on day 3) testosterone again did not show a circadian rhythm. Under treatment with dexamethasone and fluoxymesterone the overall 24 h mean of testosterone from day 2 to 3 was 44.2% of the basal level, which was significantly different from the overall mean under treatment with dexamethasone only (61.3%, n = 10, P < 0.02). Following cessation of the 24 h treatment with dexamethasone, testosterone increased slowly from 58.6% of the baseline level (overall mean from 0800 to 1000h on day 2) to 90.4% on day 4 and did not resume a circadian rhythm until day 4-5. To exclude the possibility that dexamethasone may act by attenuating the Leydig cell response to LH, 10 normal adult males were given i.v. injections of 100 μg GnRH at 1 h intervals from 1400 to 2100h with and without 10 h pretreatment with dexamethasone. Neither the pituitary response to GnRH nor the Leydig cell response to LH was modified. On the basis of these and earlier findings it is concluded that dexamethasone abolishes the circadian rhythm of testosterone by blocking the nocturnal rise. Following cessation of treatment with dexamethasone, testosterone does not resume a circadian rhythm until basal levels are reached 48 h later. This is in contrast to plasma cortisol, where a circadian rhythm reappears much earlier while it is still suppressed. © 1979.