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Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.
J Clin Endocrinol Metab. 1999 Jun; 84(6):2170-6.JC

Abstract

The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

Authors+Show Affiliations

Department of Endocrinology, Medical University Hospital 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

10372727

Citation

Arlt, W, et al. "Biotransformation of Oral Dehydroepiandrosterone in Elderly Men: Significant Increase in Circulating Estrogens." The Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 6, 1999, pp. 2170-6.
Arlt W, Haas J, Callies F, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab. 1999;84(6):2170-6.
Arlt, W., Haas, J., Callies, F., Reincke, M., Hübler, D., Oettel, M., Ernst, M., Schulte, H. M., & Allolio, B. (1999). Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. The Journal of Clinical Endocrinology and Metabolism, 84(6), 2170-6.
Arlt W, et al. Biotransformation of Oral Dehydroepiandrosterone in Elderly Men: Significant Increase in Circulating Estrogens. J Clin Endocrinol Metab. 1999;84(6):2170-6. PubMed PMID: 10372727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. AU - Arlt,W, AU - Haas,J, AU - Callies,F, AU - Reincke,M, AU - Hübler,D, AU - Oettel,M, AU - Ernst,M, AU - Schulte,H M, AU - Allolio,B, PY - 1999/6/18/pubmed PY - 1999/6/18/medline PY - 1999/6/18/entrez SP - 2170 EP - 6 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 84 IS - 6 N2 - The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/10372727/Biotransformation_of_oral_dehydroepiandrosterone_in_elderly_men:_significant_increase_in_circulating_estrogens_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.84.6.5789 DB - PRIME DP - Unbound Medicine ER -