Adrenal steroids in serum during danazol therapy, taking into account cross-reactions between danazol metabolites and serum androgens.
To investigate the changes in the serum androgen concentrations and the Free Androgen Index (FAI) in women during danazol therapy, we measured the serum concentrations of adrenal steroids and danazol metabolites, and then examined the effects of danazol metabolites on assays for serum androgens. Thirteen women who had endometriosis were treated with danazol (300 or 400 mg/day) for 8 to 16 weeks. Blood samples were taken before, during, and after the medication. During the danazol therapy, serum testosterone (T), cortisol (F), and sex-hormone binding globulin (SHBG) significantly decreased (P < 0.05); but serum dehydroepiandrosterone-sulfate (DHEAS) and FAI increased (P < 0.05). The serum concentrations of danazol metabolites were: danazol, 209.0 +/- 28.3 (ng/mL, mean +/- SEM); delta 1-2-hydroxymethyl ethisterone, 114.4 +/- 8.4; and 2-hydroxymethyl ethisterone, 660.0 +/- 54.2. There was considerable cross-reaction between danazol metabolites and androgens [T, androstenedione (A), and dehydroepiandrosterone (DHEA)] in the direct assays. As for the ratios of adrenal steroids in serum, the DHEAS/F, DHEAS/DHEA, and 11-deoxycortisol (S)/F ratios increased (P < 0.05). We conclude that the increase in FAI and DHEAS represents increased native androgenic activity with danazol, and the changes in adrenal steroid ratios in serum indicate the inhibition of 11 beta-hydroxylase and sulfatase activities during danazol therapy.
Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, Japan.
K
K
Murakami
T
T
Nakagawa
G
G
Yamashiro
K
K
Araki
K
K
Akasofu
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology; D000328:Adult; D000367:Age Factors; D000728:Androgens / Q000097:blood*; D001192:Arylsulfatases / Q000037:antagonists & inhibitors; D003350:Cortodoxone / Q000097:blood; D003613:Danazol / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004715:Endometriosis / Q000097:blood / Q000188:drug therapy; D005003:Ethisterone / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors; D043266:Steryl-Sulfatase; D013739:Testosterone / Q000097:blood*
D000728:Androgens; D012738:Sex Hormone-Binding Globulin; C051071:2-(hydroxymethyl)ethisterone; D013739:Testosterone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D013252:Steroid 11-beta-Hydroxylase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; D003613:Danazol; D005003:Ethisterone; D003350:Cortodoxone; D006854:Hydrocortisone