Adrenal Steroids in Serum during Danazol Therapy, Taking into Account Cross-Reactions between Danazol Metabolites and Serum Androgens.

K Murakami, Kouichi Murakami, Toshinobu Nakagawa, T Nakagawa, G Yamashiro, K Araki, K Akasofu, Kazutomo Akasofu
Endocrine journal · 1993 · vol. 40(6) , pp. 659–664 · doi:10.1507/endocrj.40.659 · PMID:7951534 · W2062552741
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This study measured serum steroids and danazol metabolites in women with endometriosis treated with danazol, finding decreased testosterone and cortisol, increased DHEAS and FAI, and significant cross-reactivity of metabolites in assays.

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This study measured serum androgen-related parameters and adrenal steroid concentrations in 13 women with endometriosis treated with danazol (300 or 400 mg/day) for 8–16 weeks, with blood sampling before, during, and after therapy. During danazol treatment, serum testosterone, cortisol, and sex-hormone binding globulin decreased, while serum DHEA-sulfate and the Free Androgen Index increased; danazol metabolite levels were quantified, and direct androgen assays showed considerable cross-reaction between danazol metabolites and several serum androgens. The authors report increased adrenal steroid ratios (DHEAS/F, DHEAS/DHEA, and 11-deoxycortisol/F) and conclude that FAT and DHEAS increases reflect increased native androgenic activity and that the ratio changes indicate inhibition of 11β-hydroxylase and sulfatase during therapy, while acknowledging assay cross-reaction as a key interpretive factor. This paper is centrally about endometriosis—danazol therapy effects on serum adrenal steroids and androgen measurements in women with endometriosis.

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Abstract

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.
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Adrenal Steroids in Serum during Danazol Therapy, Taking into Account Cross-Reactions between Danazol Metabolites and Serum Androgens 1993 Volume 40 Issue 6 Pages 659-664 Details Abstract To investigate the changes in the serum androgen concentrations and the Free Androgen Index (FAT) 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); 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 FAT and DHEAS represents increased native androgenic activity with danazol, and the changes in adrenal steroid ratios in serum indicate the inhibition of 11β-hydroxylase and sulfatase activities during danazol therapy. © The Japan Endocrine Society Favorites & Alerts Recently viewed articles Predecessor

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endometriosis

MeSH descriptors

Androgens Danazol Hydrocortisone Sex Hormone-Binding Globulin Testosterone Adrenal Glands Adrenal Glands Adrenal Glands Adult Age Factors Androgens Arylsulfatases Arylsulfatases Cortodoxone Cortodoxone Danazol Danazol Danazol Dehydroepiandrosterone Dehydroepiandrosterone

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