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Marked Decline in Serum Concentrations of Adrenal C19 Sex Steroid Precursors and Conjugated Androgen Metabolites During Aging
Abstract
The present data show a dramatic decline in the circulating levels of dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androst-5-ene-3β,17β-diol (5-diol), 5-diol-sulfate, 5-diol-fatty acid esters, and androstenedione in both men and women between the ages of 20–80 yr. In the 50- to 60-yr-old group, serum DHEA decreased by 74% and 70% from its peak values in 20- to 30-yr-old men and women, respectively. The serum concentrations of the conjugated metabolites of dihydrotestosterone (DHT), namely androsterone (ADT)-G, androstane-3α,17β-diol (3α-diol-G), androstane-3β,17β-diol (3β-diol-G), and ADT-sulfate are the most reliable parameters of the total androgen pool in both men and women, whereas serum testosterone and DHT can be used as markers of testicular secretion in men and interstitial ovarian secretion in women. The serum concentration of these various conjugated androgen metabolites decreased by 40.8% to 72.8% between the 20- to 30-yr-old and 70- to 80-yr-old age groups in men and women, respectively, thus suggesting a parallel decrease in the total androgen pool with age. As estimated by measurement of the circulating levels of these conjugated metabolites of DHT, it is noteworthy that women produce approximately 66% of the total androgens found in men. In women, most of these androgens originate from the transformation of DHEA and DHEA-S into testosterone and DHT in peripheral intracrine tissues, whereas in men the testes and DHEA and DHEA-S provide approximately equal amounts of androgens at the age of 50–60 yr. An additional potentially highly significant observation is that the majority of the marked decline in circulating adrenal C19 steroids and their resulting androgen metabolites takes place between the age groups of 20- to 30-yr olds and 50- to 60-yr-olds, with smaller changes are observed after the age of 60 yr.
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“Dihydroepiandrosterone sulphate is a precursor to testosterone, with concentrations that also decrease with ageing—in men aged 70–80 years, dihydroepiandrosterone sulphate concentrations are only about 20% of their peak concentrations at the age of 20 years.78”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [78]
In the citing paper
“in the 50-to 60-yr-old age group, serum DHEA has already decreased by 70%, compared with the 20-to 30-yr-old peak values (Ref.23; Fig. 1).”
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 [23]
In the citing paper
“Serum androgens as well as their precursors and metabolites decrease from the age of 30 -40 yr in women”
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 [23]
In the citing paper
“As assessed by measurement of the circulating levels of these conjugated metabolites of DHT, it can be estimated that women produce approximately 71% or two thirds of the total androgens synthesized in men (Table 1);”
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 [23]
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 [23]
In the citing paper
“the changes in precursor androgen secretion by the adrenals precede by 10 -20 yr the detectable decrease in ovarian steroidogenesis that occurs abruptly at menopause (23).”
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 [23]
In the citing paper
“in women, most of these androgens originate from the transformation of DHEA and DHEA-S into testosterone and DHT in peripheral intracrine tissues.”
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 [23]
In the citing paper
“thus suggesting a parallel decrease in the total androgen pool with age (23).”
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 [23]
In the citing paper
“The serum concentration of the aboveindicated conjugated androgen metabolites decreases by 47.5-72.7% between the 20-to 30-and 70-to 80-yr age groups in women,”
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 [23]
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 [23]
In the citing paper
“the pool of androgens in women decreases progressively from the age of 30 yr in parallel with the decrease in the serum concentration of DHEA and DHEA-S (23).”
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 [23]
In the citing paper
“The decline of testosterone and DHEA (23,26,321,322) with age could be at least partially responsible for sarcopenia in older men and women.”
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 [23]
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Citations
Cites
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Self-citationChanges in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men
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Self-citationComplete androgen blockade for the treatment of prostate cancer.
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Self-citationDHEA and peripheral androgen and estrogen formation: intracrinology
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Sex Steroids and the Construction and Conservation of the Adult Skeleton
Riggs, B. L., Khosla, S., & Melton, L. J. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.3.0465 · Cited by 1,846
Practice Bulletin No. 183: postpartum hemorrhage
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Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases
Kalyani, R. R., Corriere, M., & Ferrucci, L. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70034-8 · Cited by 1,102
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
Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy
Davison, S. L., Bell, R., Donath, S., Montalto, J. G., & Davis, S. R. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0212 · Cited by 998
Metadata
- Authors
- Labrie, F., Bélanger, A., Cusan, L., Gomez, J.-L., & Candas, B.
- Affiliations
- Centre hospitalier universitaire de Québec (CA)
- Laboratory of Molecular Endocrinology, CHUL Research Center, Le Centre Hospitalier Universitaire de Québec, and Laval University, Québec, G1V 4G2, Canada
- ORCID
- Candas, Bernard
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-08-01
- Volume
- 82
- Issue
- 8
- Pages
- 2396-2402
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2009110883
- Cited by
- 713
- References
- 37
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 4 · 2023: 24 · 2022: 22 · 2021: 17 · 2020: 15 · 2019: 25 · 2018: 28 · 2017: 28 · 2016: 18 · 2015: 18 · 2014: 31 · 2013: 25 · 2012: 39
- FWCI
- 13.82
- 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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- aging, dehydroepiandrosterone, DHEA sulfate, androstenedione, dihydrotestosterone, androstanol, androgen metabolism, sex steroids, sex differences
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Androgens, Androstenedione, Dehydroepiandrosterone, Female, Humans, Male, Middle Aged, Pregnenolone, Protein Precursors, Reference Values, Gonadal Steroid Hormones, Dihydrotestosterone, 17-Hydroxysteroid Dehydrogenases, Androstenediol, Dehydroepiandrosterone Sulfate
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