Pituitary and Testicular Function Studies. I. Experience with a New Gonadal Inhibitor, 17α-Pregn-4-en-20-yno-(2,3-d) isoxazol-17-ol (Danazol)1

Abstract

The effects of an ethinyl testosterone analogue, 17α-pregn-4-en-20-yno-(2,3-d) isoxazol-17-ol (Danazol), on the pituitary-testicular function of normal males are described. This compound has been shown to have an impeded androgenic effect in hypophysectomized male rats but no estrogenic or progestational activity. When administered to adult human males in doses of 200 or 600 mg daily, Danazol produced decreases in plasma levels of testosterone (T) and androstenedione (A) which were dose related. Changes in plasma steroid concentration were associated with symptoms of androgen withdrawal. Despite the marked reduction in plasma T, serum LH titers remained unchanged with the low dose but declined with the high dose schedule. Urinary FSH excretion titers decreased only during the high dose schedules of Danazol. HCG restored T to normal levels in the Danazol treated men within 4 days. Clomiphene administration produced increased serum LH and T levels in Danazol treated men as well as in untreated men. Plasma levels of dehydroepiandrosterone declined after 11 weeks of 600 mg of Danazol; base line cortisol levels and adrenal responsiveness to ACTH were not significantly different from those observed in untreated normal males. No uniform changes in sperm concentration or morphology were noted. It appears that Danazol may exert a dual effect in normal men: 1) inhibition of gonadotropin release and 2) direct inhibition of Leydig cell androgen synthesis.