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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]
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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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