The effects of fadrozole hydrochloride on aldosterone secretion in healthy male subjects.
The aim of this double blind placebo-controlled cross-over study was to evaluate the effects of fadrozole, a new oral nonsteroidal aromatase inhibitor, on basal and stimulated cortisol and aldosterone secretion at a daily dosage of 4 mg given for 14 days to eight healthy men. After 2 weeks of treatment, fadrozole, compared with placebo, effectively suppressed plasma estrogen levels (P less than 0.05 at 0800 h), but did not affect glucocorticoid secretion either under basal conditions or after stimulation with ACTH. Basal plasma aldosterone levels were not significantly different with fadrozole treatment compared to those after placebo treatment. However, compared with pretreatment values, basal aldosterone secretion appeared impaired (P less than 0.05). A statistically significant blunting of the responses of plasma aldosterone to ACTH (P less than 0.01) and upright posture (P less than 0.01) after fadrozole compared with placebo treatment further indicated that fadrozole impaired basal aldosterone secretion. This attenuation of aldosterone secretion was accompanied by a rise of PRA in the basal condition (P = 0.05) and after stimulation by 40 mg furosemide (P less than 0.01) and upright posture (P less than 0.01). An increase in deoxycorticosterone was observed after fadrozole treatment compared with pretreatment values (P less than 0.01) and after stimulation with ACTH compared with placebo (P less than 0.05). This study confirms that fadrozole given in daily doses of 4 mg is an effective aromatase inhibitor which does not affect glucocorticoid secretion. However, this dose may induce an impairment of aldosterone secretion which is modest and revealed mainly under specific stimulatory conditions, and does not lead to clinical symptoms of hemodynamic dysregulation or a relevant disturbance of serum electrolytes.
Trunet
P F
PF
Research and Development Department, Ciba-Geigy Ltd., Basel, Switzerland.
Mueller
P
P
Girard
F
F
Aupetit
B
B
Bhatnagar
A S
AS
Zognbi
F
F
Ezzet
F
F
Menard
J
J
D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D003366:Cosyntropin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004970:Estrone / Q000097:blood; D017316:Fadrozole; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D011187:Posture; D012016:Reference Values; D012083:Renin / Q000097:blood
D004965:Estrogen Antagonists; D007093:Imidazoles; D009570:Nitriles; D003366:Cosyntropin; D004970:Estrone; D003900:Desoxycorticosterone; D000450:Aldosterone; D004958:Estradiol; D005665:Furosemide; D012083:Renin; D017316:Fadrozole; D006854:Hydrocortisone