The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Feb 1994
Randomized Controlled Trial Clinical TrialAdministration of RU 486 for 8 days in normal volunteers: antiglucocorticoid effect with no evidence of peripheral cortisol deprivation.
New therapeutic indications based on the antiprogesterone action of RU 486 (Mifepristone) are emerging which require long term administration and raise the question of its safety because of the antiglucocorticoid action of the drug. A trial was designed to assess the antiglucocorticoid effect of RU 486, possible manifestations of peripheral cortisol deprivation, and the adrenocortical and corticotroph reserves. Ten normal male volunteers (aged 21-29 yr) were given RU 486 (200 mg/day) or placebo between 0800-0900 h for 8 consecutive days in a randomized, double blind, cross-over design, with a 1-month interval between the two periods. ⋯ Direct pituitary stimulation (100 micrograms ovine CRH, followed by 1 IU lysine vasopressin over 15 min) also induced exaggerated corticotroph and adrenocortical responses (P < 0.005); peak values before and at the end of treatment were, respectively: plasma ACTH, 147.7 +/- 24.6 and 254.0 +/- 41.3 pg/mL; and plasma cortisol, 231.6 +/- 7.3 and 319.2 +/- 12.3 ng/mL. These data show that 8-day treatment with 200 mg RU 486 daily induces a hormonally detectable antiglucocorticoid effect without clinical symptoms. This state results from reversible cortisol overproduction with preservation of adrenocortical and pituitary reserves.