Effect of clomiphene citrate on testicular steroid metabolism in man

Administration of clomiphene citrate to males with normal peripheral testosterone levels increased the serum levels of FSH, LH, testosterone and low polar oestrogens and also the urinary excretion of LH, low polar oestrogens, dehydroepiandrosterone, androsterone and aetiocholanolone. No significant change was noted for the urinary excretion of 17-oxogenic steroids. Addition of clomiphene citrate (10(-4) to 2 X 10(-3) M) to incubations of [7-3H, 21-14C] progesterone with human testicular biopsy specimens in vitro caused a slight inhibition in the formation of 17 alpha-hydroxyprogesterone and a slightly increased formation of 20 alpha-hydroxy-4-pregnen-3-one but no measurable changes in the C19 steroid formation. The results support the hypothesis that there is selective action of clomiphene citrate upon the adrenal C19 steroid biosynthesis in the human male, combined with an indirect effect upon the testes via the hypothalamic-pituitary system. A direct effect on the gonadal steroidogenesis can, however, not be ruled out.