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Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression.
J Clin Endocrinol Metab. 1998 Jun; 83(6):1928-34.JC

Abstract

Women with adrenal insufficiency suffer from chronic dehydroepiandrosterone (sulfate) [DHEA(S)] deficiency. To define a suitable dose for DHEA replacement, we studied the pharmacokinetics and biotransformation of orally administered DHEA in nine healthy female volunteers (mean age 23.3 +/- 4.1 yr, mean body mass index 22.5 +/- 1.8 kg/m2) with transient suppression of adrenal androgen secretion because of dexamethasone (dex) administration (4 x 0.5 mg/day for 4 days). Diurnal blood sampling was performed during the early follicular phase of four subsequent menstrual cycles (study period 1: baseline; study periods 2-4: dex + placebo, dex + 50 mg DHEA or dex + 100 mg DHEA in a randomized cross-over design). Dex induced not only a significant suppression of serum cortisol (to 8% of baseline) but also of DHEA (18%), DHEA(S) (16%), and androstenedione (26%), as well as of testosterone (28%), dihydrotestosterone (43%), and estrone (54%). Oral administration of 50 mg DHEA led to restoration of DHEA(S) baseline levels, whereas 100 mg induced supraphysiological concentrations [baseline vs. 50 mg DHEA vs. 100 mg DHEA: area under the concentration-time curve (AUC) 0-12 h DHEA: 280 +/- 85 vs. 241 +/- 73 vs. 383 +/- 106 nmol/L x h; AUC 0-12 h DHEA(S): 89.1 +/- 48.4 vs. 139.6 +/- 43.5 vs. 213.3 +/- 21.6 mumol/L x h). Serum concentrations of dihydrotestosterone and estrone were restored to baseline after 50 mg DHEA, whereas baseline testosterone and androstenedione levels were only achieved by administration of 100 mg DHEA. In conclusion, 50 mg DHEA seems to be a suitable replacement dose in females with adrenal insufficiency. Furthermore, the rapid and lasting conversion to potent androgens demonstrates a potential role of DHEA for androgen replacement in females in general.

Authors+Show Affiliations

Department of Endocrinology, Medical University Clinic Wuerzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

9626121

Citation

Arlt, W, et al. "Oral Dehydroepiandrosterone for Adrenal Androgen Replacement: Pharmacokinetics and Peripheral Conversion to Androgens and Estrogens in Young Healthy Females After Dexamethasone Suppression." The Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 6, 1998, pp. 1928-34.
Arlt W, Justl HG, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab. 1998;83(6):1928-34.
Arlt, W., Justl, H. G., Callies, F., Reincke, M., Hübler, D., Oettel, M., Ernst, M., Schulte, H. M., & Allolio, B. (1998). Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. The Journal of Clinical Endocrinology and Metabolism, 83(6), 1928-34.
Arlt W, et al. Oral Dehydroepiandrosterone for Adrenal Androgen Replacement: Pharmacokinetics and Peripheral Conversion to Androgens and Estrogens in Young Healthy Females After Dexamethasone Suppression. J Clin Endocrinol Metab. 1998;83(6):1928-34. PubMed PMID: 9626121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. AU - Arlt,W, AU - Justl,H G, AU - Callies,F, AU - Reincke,M, AU - Hübler,D, AU - Oettel,M, AU - Ernst,M, AU - Schulte,H M, AU - Allolio,B, PY - 1998/6/17/pubmed PY - 1998/6/17/medline PY - 1998/6/17/entrez SP - 1928 EP - 34 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 83 IS - 6 N2 - Women with adrenal insufficiency suffer from chronic dehydroepiandrosterone (sulfate) [DHEA(S)] deficiency. To define a suitable dose for DHEA replacement, we studied the pharmacokinetics and biotransformation of orally administered DHEA in nine healthy female volunteers (mean age 23.3 +/- 4.1 yr, mean body mass index 22.5 +/- 1.8 kg/m2) with transient suppression of adrenal androgen secretion because of dexamethasone (dex) administration (4 x 0.5 mg/day for 4 days). Diurnal blood sampling was performed during the early follicular phase of four subsequent menstrual cycles (study period 1: baseline; study periods 2-4: dex + placebo, dex + 50 mg DHEA or dex + 100 mg DHEA in a randomized cross-over design). Dex induced not only a significant suppression of serum cortisol (to 8% of baseline) but also of DHEA (18%), DHEA(S) (16%), and androstenedione (26%), as well as of testosterone (28%), dihydrotestosterone (43%), and estrone (54%). Oral administration of 50 mg DHEA led to restoration of DHEA(S) baseline levels, whereas 100 mg induced supraphysiological concentrations [baseline vs. 50 mg DHEA vs. 100 mg DHEA: area under the concentration-time curve (AUC) 0-12 h DHEA: 280 +/- 85 vs. 241 +/- 73 vs. 383 +/- 106 nmol/L x h; AUC 0-12 h DHEA(S): 89.1 +/- 48.4 vs. 139.6 +/- 43.5 vs. 213.3 +/- 21.6 mumol/L x h). Serum concentrations of dihydrotestosterone and estrone were restored to baseline after 50 mg DHEA, whereas baseline testosterone and androstenedione levels were only achieved by administration of 100 mg DHEA. In conclusion, 50 mg DHEA seems to be a suitable replacement dose in females with adrenal insufficiency. Furthermore, the rapid and lasting conversion to potent androgens demonstrates a potential role of DHEA for androgen replacement in females in general. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/9626121/Oral_dehydroepiandrosterone_for_adrenal_androgen_replacement:_pharmacokinetics_and_peripheral_conversion_to_androgens_and_estrogens_in_young_healthy_females_after_dexamethasone_suppression_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.83.6.4850 DB - PRIME DP - Unbound Medicine ER -