title: Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.
abstract: In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients.
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism; D004285:Dogs; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006177:Gynecomastia / Q000139:chemically induced; D007093:Imidazoles / Q000009:adverse effects* / Q000378:metabolism; D007654:Ketoconazole; D008297:Male; D010879:Piperazines / Q000009:adverse effects* / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D007093:Imidazoles; D010879:Piperazines; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D007654:Ketoconazole