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Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology.
Abstract
This study analyzes in detail the serum concentration of the active androgens and estrogens, as well as a series of free and conjugated forms of their precursors and metabolites, after daily application for 2 weeks of 10 mL 20% dehydroepiandrosterone (DHEA) solution on the skin to avoid first passage through the liver. In men, DHEA administration caused 175%, 90%, 200% and 120% increases in the circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid esters, and androst-5-ene-3 beta,17 beta-diol, respectively, with a return to basal values 7 days after cessation of the 14-day treatment. Serum androstenedione increased by approximately 80%, whereas serum testosterone and dihydrotestosterone (DHT) remained unchanged. In parallel with the changes in serum DHEA, the concentrations of the conjugated metabolites of DHT, namely androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, and androstane-3 beta,17 beta-diol-G increased by about 75%, 50%, and 75%, respectively, whereas androsterone-sulfate increased 115%. No consistent change was observed in serum estrone (E1) or estradiol (E2) in men receiving DHEA, whereas serum E1-sulfate and E2-sulfate were slightly and inconsistently increased by about 20%, and serum cortisol and aldosterone concentrations were unaffected by DHEA administration. Almost superimposable results were obtained in women for most steroids except testosterone, which was about 50% increased during DHEA treatment. This increase corresponded to about 0.8 nM testosterone, an effect undetectable in men because they already have much higher (approximately 15 nM) basal testosterone levels. In women, the serum levels of the conjugated metabolites of DHT, namely androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, androstane-3 beta,17 beta-diol-G, and androsterone-sulfate were increased by 125%, 140%, 120% and 150%, respectively. The present study demonstrates that the serum concentrations of testosterone, DHT, E1, and E2 are poor indicators of total androgenic and estrogenic activity. However, the esterified metabolites of DHT appear as reliable markers of the total androgen pool, because they directly reflect the intracrine formation of androgens in the tissues possessing the steroidogenic enzymes required to transform the inactive precursors DHEA and DHEA-S into DHT. As well demonstrated in women, who synthesize almost all their androgens from DHEA and DHEA-S, supplementation with physiological amounts of exogeneous DHEA permits the biosynthesis of androgens limited to the appropriate target tissues without leakage of significant amounts of active androgens into the circulation. This local or intracrine biosynthesis and action of androgens eliminates the inappropriate exposure of other tissues to androgens and thus minimizes the risks of undesirable masculinizing or other androgen-related side effects of DHEA.
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“DHEA serves as a precursor to many androgenic and estrogenic hormones.32, 47, 48”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [32]
In the citing paper
“We then observed that changes in serum DHEA within the physiological range of young adult men and women led only to small or nonsignificant changes in serum testosterone, DHT, or E 2 , whereas, on the other hand, the concentration of the conjugated metabolites of DHT were markedly increased (27).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [27]
In the citing paper
“an estimate of the relative amount of total androgens in women and men calculated on the basis of the sum of the serum concentrations of these three metabolites suggests that total androgen production in women is more than two thirds, or 71%, of that observed in men (23,27).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [27]
In the citing paper
“women, at menopause, are not only deprived from estrogens because of a rapid loss of ovarian activity but also have been deprived from androgens for a longer period because of a progressive decrease of serum DHEA levels starting quite a few years before menopause.”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [27]
Citations
Cites
Extension of Multiple Range Tests to Group Means with Unequal Numbers of Replications
Kramer, C. Y. (1956) · Biometrics · doi:10.2307/3001469 · Cited by 3,146
ORENTREICH, N., BRIND, J. L., RIZER, R. L., & VOGELMAN, J. H. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-3-551 · Cited by 1,349
Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.
Morales, A. J., Nolan, J. J., Nelson, J. C., & Yen, S. S. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.6.7515387 · Cited by 841
Important Advances in Oncology
DeVita, V. T., Hellman, S., & Rosenberg, S. A. (1991) · Anti-Cancer Drugs · doi:10.1097/00001813-199108000-00014 · Cited by 760
Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism
Andersson, S., Berman, D. M., Jenkins, E. P., & Russell, D. W. (1991) · Nature · doi:10.1038/354159a0 · Cited by 643
Andersson, S., & Russell, D. W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3640 · Cited by 501
The key role of 17β-hydroxysteroid dehydrogenases in sex steroid biology
Labrie, F., Luu-The, V., Lin, S.-X., Claude, L., Simard, J., Breton, R., & Bélanger, A. (1997) · Steroids · doi:10.1016/s0039-128x(96)00174-2 · Cited by 480
Self-citationChanges in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men
Bèlanger, A., Candas, B., Dupont, A., Cusan, L., Diamond, P., Gomez, J.-L., & Labrie, F. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.4.7962278 · Cited by 437
Self-citationNESTLER, J. E., BARLASCINI, C. O., CLORE, J. N., & BLACKARD, W. G. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-1-57 · Cited by 414
Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice.
Coleman, D. L., Leiter, E. H., & Schwizer, R. W. (1982) · Diabetes · doi:10.2337/diab.31.9.830 · Cited by 317
The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women
MORTOLA, J. F., & YEN, S. S. C. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-3-696 · Cited by 311
Complete androgen blockade for the treatment of prostate cancer.
Labrie, F., Dupont, A., & Bèlanger, A. (1985) · PubMed · Cited by 285
Self-citationDHEA and peripheral androgen and estrogen formation: intracrinology
LABRIE, F., BÉLANGER, A., SIMARD, J., LUU‐THE, V., & LABRIE, C. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb17369.x · Cited by 280
Self-citationMIGEON, C. J., KELLER, A. R., LAWRENCE, B., & SHEPARD, T. H. (1957) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-17-9-1051 · Cited by 260
Luu-The, V., Zhang, Y., Poirier, D., & Labrie, F. (1995) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00209-x · Cited by 224
Self-citationBélanger, B., Bélanger, A., Labrie, F., Dupont, A., Cusan, L., & Monfette, G. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90514-1 · Cited by 212
Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women
Casson, P. R., Andersen, R. N., Herrod, H. G., Stentz, F. B., Straughn, A. B., Abraham, G. E., & Buster, J. E. (1993) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(93)90431-h · Cited by 211
Structure of human type II 5 alpha-reductase gene
Labrie, F., Sugimoto, Y., Luu-The, V., Simard, J., Lachance, Y., Bachvarov, D. R., Leblanc, G., Durocher, F., & Paquet, N. (1992) · Endocrinology · doi:10.1210/endo.131.3.1505484 · Cited by 203
Self-citationSimultaneous radioimmunoassay of progestins, androgens and estrogens in rat testis
Bèlanger, A., Caron, S., & Picard, V. (1980) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(80)90190-9 · Cited by 177
Self-citationAndrogenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate.
LABRIE, C., BELANGER, A., & LABRIE, F. (1988) · Endocrinology · doi:10.1210/endo-123-3-1412 · Cited by 167
Self-citationModulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone.
Gordon, G. B., Shantz, L. M., & Talalay, P. (1987) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(87)90023-9 · Cited by 159
Adrenocortical function in old age: response to acute adrenocorticotropin stimulation.
VERMEULEN, A., DESLYPERE, J. P., SCHELFHOUT, W., VERDONCK, L., & RUBENS, R. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-1-187 · Cited by 135
Labrie, F., Simard, J., Luu-The, V., Bélanger, A., & Pelletier, G. (1992) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(92)90308-6 · Cited by 132
Self-citationZumoff, B., Levin, J., Rosenfeld, R. S., Markham, M. J., Strain, G. W., & Fukushima, D. K. (1981) · PubMed · Cited by 123
Rodbard, D. (1974) · Endocrinology · doi:10.1210/endo-94-5-1427 · Cited by 116
Schriock, E. D., Buffington, C. K., Hubert, G. D., Kurtz, B. R., Kitabchi, A. E., Buster, J. E., & Givens, J. R. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-6-1329 · Cited by 115
Levels of plasma steroid glucuronides in intact and castrated men with prostatic cancer.
BÉLANGER, A., BROCHU, M., & CLICHE, J. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-62-5-812 · Cited by 108
Self-citationInhibition of tumor development by dehydroepiandrosterone and related steroids.
Schwartz, A. G., Pashko, L., & Whitcomb, J. M. (1986) · Toxicologic Pathology · doi:10.1177/019262338601400312 · Cited by 101
Science behind total androgen blockade: from gene to combination therapy.
Labrie, F., Bèlanger, A., Dupont, A., The, V. L., Simard, J., & Labrie, C. (1993) · PubMed · Cited by 91
Self-citationIDENTIFICATION AND ISOLATION OF DEHYDROISOANDROSTERONE FROM PERIPHERAL HUMAN PLASMA
Migeon, C. J., & Plager, J. E. (1954) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65504-8 · Cited by 71
Li, S., Yan, X., B�langer, A., & Labrie, F. (1994) · Breast Cancer Research and Treatment · doi:10.1007/bf00665681 · Cited by 70
Self-citationISOLATION OF DEHYDROISOANDROSTERONE SULFATE FROM NORMAL MALE URINE
Munson, P. L., Gallagher, T. F., & Koch, F. C. (1944) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)72091-7 · Cited by 68
LABRIE, Y., DUROCHER, F., LACHANCE, Y., TURGEON, C., SIMARD, J., LABRIE, C., & LABRIE, F. (1995) · DNA and Cell Biology · doi:10.1089/dna.1995.14.849 · Cited by 64
Self-citationCloning and expression of cDNA encoding human placental estrogen sulfotransferase
Bernier, F., López, I., Labrie, F., & Luu-The, V. (1994) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(94)90159-7 · Cited by 58
Self-citationStructural Characterization and Expression of the Human Dehydroepiandrosterone Sulfotransferase Gene
LUU-THE, V., Dufort, I., Paquet, N., Reimnitz, G., & Labrie, F. (1995) · DNA and Cell Biology · doi:10.1089/dna.1995.14.511 · Cited by 53
Self-citationObesity in the dog: role of the adrenal steroid dehydroepiandrosterone (DHEA).
MacEwen, E. G., & Kurzman, I. D. (1991) · The Journal of Nutrition · doi:10.1093/jn/121.suppl_11.s51 · Cited by 49
Stahl, F., Schnorr, D., Pilz, C., & Dörner, G. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211136 · Cited by 47
Bernier, F., Leblanc, G., Labrie, F., & Luu-The, V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)46914-1 · Cited by 43
Self-citationLabrie, F., Simard, J., Luu-The, V., Bèlanger, A., Pelletier, G., Morel, Y., Mébarki, F., Sánchez, R., Durocher, F., Turgeon, C., et al. (1996) · Springer eBooks · doi:10.1007/978-3-662-03230-5_10 · Cited by 34
Self-citationBèlanger, A., Labrie, F., Dupont, A., Brochu, M., & Cusan, L. (1988) · PubMed · Cited by 24
Self-citationUnconjugated and Glucuronide Steroid Levels in Human Breast Cyst Fluid
Bèlanger, A., Labrie, F., & Angeli, A. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb17795.x · Cited by 22
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Kaufman, J. M., & Vermeulen, A. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0013 · Cited by 1,079
Knop, E., Knop, N., Millar, T., Obata, H., & Sullivan, D. A. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6997c · Cited by 1,093
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Simard, J., Ricketts, M.-L., Gingras, S., Soucy, P., Feltus, F. A., & Melner, M. H. (2005) · Endocrine Reviews · doi:10.1210/er.2002-0050 · Cited by 620
Metadata
- Authors
- Labrie, F., Bélanger, A., Cusan, L., & Candas, B.
- Affiliations
- Centre hospitalier universitaire de Québec (CA)
- ORCID
- Candas, Bernard
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-08
- Volume
- 82
- Issue
- 8
- Pages
- 2403-2409
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2021443932
- Cited by
- 350
- References
- 41
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 12 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 3
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Keywords
- dehydroepiandrosterone, DHEA sulfate, androstenedione, androsterone glucuronide, androsterone sulfate, estrone sulfate, estradiol sulfate, intracrinology, steroid metabolism, sex differences, estradiol
- MeSH terms
- Administration, Cutaneous, Aged, Aldosterone, Androgens, Androstenedione, Dehydroepiandrosterone, Estradiol, Estrogens, Estrone, Fatty Acids, Female, Glucuronates, Humans, Hydrocortisone, Liver, Male, Middle Aged, Dihydrotestosterone, Testosterone, Dehydroepiandrosterone Sulfate
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