Effects of norgestrel and metyrapone on pituitary-adrenal-ovarian function.
To assess the effects of d-norgestrel on pituitary-adrenal-ovarian function, basal levels and responses to metyrapone of urinary 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS), plasma cortisol (F), plasma delta4-androstenedione (A), plasma testosterone (T), plasma estrone (E1) and estradiol (E2), plasma and urinary LH and FSH were determined in 10 normal women before and while taking d-norgestrel 1 mg/day. Cortisol secretion rate (CSR) and binding capacities of cortisol binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) were also measured. Norgestrel did not significantly alter 17-KGS, 17-KS, F, LH, FSH, CSR, or the 17-KGS and 17-KS responses to metyrapone. Norgestrel reduced TeBG binding capacity but not CBG binding capacity. Norgestrel competitively inhibited the binding of dihydrotestosterone to TeBG under in vitro conditions. Levels of T, E2, and E1 were reduced by norgestrel. All measured hormone levels except FSH were increased following metyrapone prior to norgestrel administration. Norgestrel completely blocked the metyrapone-induced increases in LH and E2 and markedly reduced the E1 increase. Metyrapone reduced E2 during norgestrel treatment.
D015065:17-Hydroxycorticosteroids / Q000652:urine; D015068:17-Ketosteroids / Q000652:urine; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000735:Androstenedione / Q000097:blood; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008797:Metyrapone / Q000494:pharmacology*; D009644:Norgestrel / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D012636:Secretory Rate; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D015065:17-Hydroxycorticosteroids; D015068:17-Ketosteroids; D004970:Estrone; D009644:Norgestrel; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone; D008797:Metyrapone