The effects of spironolactone on adrenal steroidogenesis in hirsute women.
The effect of spironolactone on adrenal androgen and cortisol production was studied in six hirsute women. Hirsute women were evaluated before and 1 month after receiving 200 mg of spironolactone daily. Basal levels of serum androgens, 17-hydroxyprogesterone (17-OHP), cortisol (F), corticosteroid-binding globulin, and plasma adrenocorticotropic hormone (ACTH) were normal and did not change with therapy. The delta maximum (delta max) responses after dexamethasone suppression and ACTH administration of dehydroepiandrosterone (DHEA), androstenedione (delta 4A), 17-hydroxypregnenolone, and 17-OHP were similar in hirsute women and ovulatory control subjects. After spironolactone administration, the delta max DHEA response was unchanged, whereas the delta max delta 4A response was decreased (P less than 0.05). The delta max ratios of DHEA/delta 4A and 17-OHP/delta 4A were significantly increased after spironolactone in hirsute women, which suggested inhibitions of 3 beta-ol-dehydrogenase-isomerase and delta 4 17,20 desmolase activities. A significant reduction in delta max F occurred after spironolactone administration (P less than 0.05). Although baseline 11-desoxycortisol (S) and the plasma S/ACTH ratio were unaltered, the delta max S/F ratio increased after treatment (P less than 0.01), suggesting an inhibition of 11 beta-hydroxylase activity. Inhibition of adrenal androgen production occurs with spironolactone, but only serum levels of delta 4A are decreased, whereas DHEA and its sulfate (DHEA-S) levels remain unchanged.
D019326:17-alpha-Hydroxyprogesterone; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000728:Androgens / Q000097:blood; D000735:Androstenedione / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006628:Hirsutism / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use*; D013256:Steroids / Q000096:biosynthesis*; D013997:Time Factors
D000728:Androgens; D006908:Hydroxyprogesterones; D013256:Steroids; D013148:Spironolactone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone; D006854:Hydrocortisone