The DOI matches its Crossref record; 337 of the 388 references it cites were found in a registry or an index; none of the 297 sources its claims cite is checked for support yet.
Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone
Abstract
Serum androgens as well as their precursors and metabolites decrease from the age of 30 -40 yr in women, thus suggesting that a more physiological hormone replacement therapy at menopause should contain an androgenic compound.It is important to consider, however, that most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin.Much progress in this new area of endocrine physiology called intracrinology has followed the cloning and characterization of most of the enzymes responsible for the transformation of DHEA and DHEA-S into androgens and estrogens in peripheral target tissues, where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation, thus seriously limiting the interpretation of serum levels of active sex steroids.The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured.In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation.In clinical studies, DHEA has been found to increase bone mineral density and to stimulate vaginal maturation without affecting the endometrium, while improving well-being and libido with no significant side effects.The advantage of DHEA over other androgenic compounds is that DHEA, at physiological doses, is converted into androgens and/or estrogens only in the specific intracrine target tissues that possess the appropriate physiological enzymatic machinery, thus limiting the action of the sex steroids to those tissues possessing the tissue-specific profile of expression of the genes responsible for their formation, while leaving the other tissues unaffected and thus minimizing the potential side effects observed with androgens or estrogens administered systemically.(Endocrine Reviews 24: 152-182, 2003) I. Androgens and Their Role in Women A. Introduction B. Decrease of serum DHEA, androgens, and their metabolites with age C. Androgens and bone physiology D. Other roles of androgens in women II.DHEA Is Predominantly Converted into Androgens in Women A. Intracrinology B. Structure of the human steroidogenic enzymes C. Women produce about two thirds of the androgens synthesized in men III.Androgens Inhibit Breast Cancer A. Clinical data B. Preclinical data IV.DHEA Inhibits Breast Cancer A. Preclinical studies B. Epidemiological studies C. DHEA and other cancers V. Rationale for the Use of DHEA as a Source of Androgens in Postmenopausal Women A. Tissue-specific androgenic and/or estrogenic activity of DHEA B. Benefits of DHEA in postmenopausal women
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TL;DR
This review argues that women produce substantial androgens, largely via peripheral intracrine conversion of adrenal DHEA/DHEA-S, and that these androgens decline with age. It synthesizes preclinical and clinical evidence that androgens and DHEA inhibit breast cancer and that physiological DHEA replacement may benefit postmenopausal women without stimulating the endometrium.
Key findings
- Serum DHEA falls by 70% in 50–60-year-old women versus 20–30-year-old peak values, and mean serum testosterone decreases from approximately 1.3 to 0.61 nM between ages 21 and 40.
- Based on serum ADT-G, 3α-diol-G, and 3β-diol-G, women produce about 71% (“two thirds”) of the total androgens synthesized in men, mostly from peripheral intracrine conversion of DHEA/DHEA-S.
- Androgens/DHEA inhibit breast cancer in models: DHT blocked E2-stimulated ZR-75-1 growth; DHEA reduced DMBA tumor incidence to 22%, 11%, and 3.8% at serum DHEA levels of 7.09, 17.5, and 27.2 nM versus 68% in controls; DHEA inhibited ZR-75-1 xenograft growth by 50.4%, 76.8%, and 80.0% at 0.3, 1.0, and 3.0 mg/day.
- In a 12-month study of 60–70-year-old women (n=15), percutaneous 10% DHEA increased bone mineral density by 2.3% at the hip, 3.75% at Ward’s triangle, and 2.2% at the lumbar spine, with no endometrial stimulation; fasting glucose and insulin decreased by 12% and 17%, respectively.
Methods
- Narrative review integrating the author’s and others’ endocrine, preclinical, and clinical studies; no systematic search or meta-analysis is described.
- Evidence includes serum steroid/metabolite measurements across ages, DHEA administration studies, human breast cancer cell lines (ZR-75-1, MCF-7), DMBA-induced rat mammary carcinoma, nude mouse xenografts, and clinical DHEA replacement studies.
- Main analysis is descriptive synthesis comparing intracrine enzyme expression, serum androgen metabolites, tumor outcomes, and bone/clinical endpoints.
Limitations
- The paper states that serum testosterone and E2 poorly reflect intracellular/intracrine androgen and estrogen activity, and that animal models such as rats, mice, and guinea pigs do not secrete significant adrenal DHEA/DHEA-S, limiting translation.
- The paper notes contradictory epidemiological data on androgens and breast cancer risk, attributed to small cancer numbers, methodology, and low predictive value of serum sex steroid measurements; it also notes possible differences in metabolic clearance rates affecting androgen-pool estimates.
- Evident from the text: this is a narrative review, not a systematic review, and many key preclinical and clinical findings come from the author’s group; the described 12-month DHEA clinical study had n=15 and the text does not report a control group.
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In the 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);”
- Also stated in: § C. Women produce about two thirds of the androgens synthesized in men · plain
“C. Women produce about two thirds of the androgens synthesized in men”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Table 1
- Not checked yetcites [23] Labrie, 1997, Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging., J Clin Endocrinol Metab source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § C. Women produce about two thirds of the androgens synthesized in men · plain
None of the sources cited for this claim have been checked yet.
In the paper
“treatment with DHEA caused an increase in serum ADT-G, 3␣-diol-G, and 3diol-G of approximately 125% (Fig. 13A), 140% (Fig. 13B), and 120% (Fig. 13C), respectively.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Fig. 13A
- Not checked yetcites Fig. 13B
- Not checked yetcites Fig. 13C
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“whereas serum 4-dione and testosterone increased by about 100% and 50% over control, respectively (Fig. 12).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Fig. 12
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“between the ages of 21 and 40 yr, mean serum testosterone in normal women decreases from approximately 1.3 to 0.61 nm (Ref.26; Fig. 2).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Ref.26
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“in the 50-to 60-yr-old group, serum DHEA has already decreased by 70% from its 20-to 30-yr-old peak values in women (Fig. 1).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Fig. 1
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“only a small proportion, estimated at 10 -15% of the intracellular content of these androgens, diffuses out of the intracellular compartment without prior metabolism and can be measured as active androgen in the circulation.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the 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,”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites [23] Labrie, 1997, Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging., J Clin Endocrinol Metab source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No significant effect was observed on serum E 1 , E 2 , or DHT.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in the absence of E 2 , EM-139 and DHT alone caused 21% (P Ͻ 0.01) and 43% (P Ͻ 0.01) inhibitions of basal cell growth, respectively.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“the first demonstration of a potent and direct inhibitory effect of androgens on human breast cancer growth was obtained in the estrogensensitive human breast cancer cell line ZR-75-1 (208).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [208] Poulin, 1988, Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line., Breast Cancer Res Treat source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- The quote only partly states this claim. 3
- It may state two separate claims as one. 54
- Probably not a substantial claim. 1
In the 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).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Decrease of serum DHEA, androgens, and their metabolites with age
What the sources say
- Not checked yetcites [27] Labrie, 1997, Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology., J Clin Endocrinol Metab source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
In the paper
“After daily administration of a single dose of DHEA percutaneously, serum DHEA, DHEA-S, and DHEA fatty acid esters increased approximately 175%, 130%, and 250% above control, respectively (Fig. 11),”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
What the sources say
- Not checked yetcites Fig. 11
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present data show that elevations in serum DHEA within the physiological range found in young adult women led to only small or even no significant changes in serum testosterone, DHT, or E 2 , whereas, by contrast, the concentrations of the conjugated metabolites of DHT are markedly elevated,”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“4-Dione also led to significant growth inhibition in ZR-75-1 cells, although the active concentrations (IC 50 , 15 nm) are in the upper range of the plasma concentrations (1-10 nm) found in women (215-218).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [215] Rochefort, 1983, The estrogenic and antiestrogenic activities of androgens in female target tissues., Pharmacol Ther source
- Not checked yetcites [216] Abraham, 1974, Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle., J Clin Endocrinol Metab source
- Not checked yetcites [217] Vermeulen, 1979, Factors affecting sex hormone levels in postmenopausal women., J Steroid Biochem source
- Not checked yetcites [218] Mistry, 1986, Endogenous C19-steroids and estradiol levels in human primary breast tumor tissues and their correlation with androgen and estrogen receptors., J Steroid Biochem source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the pure steroidal antiestrogen EM-139 (228), on the other hand, not only completely reversed the effect of E 2 but further inhibited cell number by 30% below control values (P Ͻ 0.01; Fig. 18B).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [228] Lévesque, 1991, Synthesis and biological activity of new halo-steroidal antiestrogens., J Med Chem source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“DHT not only completely blocked the stimulatory effect of E 2 on cell proliferation but also reduced cell growth in the absence of estrogens.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [208] Poulin, 1988, Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line., Breast Cancer Res Treat source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In ZR-75-1 cells, concentrations of DHT in the incubation medium similar to the plasma levels found in normal women (215-217) and breast cancer patients (Ref.218; 0.3-0.7 nm) are potent inhibitors of the mitogenic effect of E 2 and even inhibit growth in the absence of estrogens (208).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [208] Poulin, 1988, Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line., Breast Cancer Res Treat source
- Not checked yetcites [215] Rochefort, 1983, The estrogenic and antiestrogenic activities of androgens in female target tissues., Pharmacol Ther source
- Not checked yetcites [216] Abraham, 1974, Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle., J Clin Endocrinol Metab source
- Not checked yetcites [217] Vermeulen, 1979, Factors affecting sex hormone levels in postmenopausal women., J Steroid Biochem source
- Not checked yetcites [218] Mistry, 1986, Endogenous C19-steroids and estradiol levels in human primary breast tumor tissues and their correlation with androgen and estrogen receptors., J Steroid Biochem source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“it was found that the growth-inhibitory effect of DHT is clearly additive to that induced by maximally effective concentra- tions of the antiestrogen LY156758, thus indicating an action mediated by a mechanism different from interaction with the estrogen receptor (ER; 229).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
What the sources say
- Not checked yetcites [229] de Launoit, 1991, Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells., Cancer Res
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with DHT, on the other hand, not only completely reversed the stimulatory effect of E 2 on tumor growth but also decreased total tumor area to 48 Ϯ 10% of its original size.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The androgenic effect was observed at subnanomolar concentrations of the nonaromatizable androgen DHT, regardless of the presence of estrogens, and was competitively reversed by the antiandrogen hydroxyflutamide.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, the antiproliferative activity of androgens in estrogen-deprived ZR-75-1 cells is more pronounced and is additive to that exerted by antiestrogens (208,241).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
What the sources say
- Not checked yetcites [208] Poulin, 1988, Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line., Breast Cancer Res Treat source
- Not checked yetcites [241] Poulin, 1989, Antiestrogenic properties of keoxifene trans-4-hydroxytamoxifen, and ICI 164384, a new steroidal antiestrogen, in ZR-75-1 human breast cancer cells., Breast Cancer Res Treat source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The inhibition constant (K i ) value for the reversal of DHT action by hydroxyflutamide was estimated at 39 nm (233), in agreement with the affinity of the antagonist for the AR (227).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
What the sources say
- Not checked yetcites [233] Cheng, 1973, Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I50) on an enzymatic reaction., Biochem Pharmacol source
- Not checked yetcites [227] Simard, 1986, Characteristics of interaction of the antiandrogen flutamide with the androgen receptor in various target tissues., Mol Cell Endocrinol source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the size of the ZR-75-1 tumors increased by 9.4-fold over a 291-d period (9.5 months) in ovariectomized nude mice supplemented with E 1 ; in contrast, in control ovariectomized mice that received the vehicle alone, tumor size decreased to 36.9% of the initial value during the course of the study (265).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [265] Couillard, 1998, Effect of dehydroepiandrosterone and the antiestrogen EM-800 on the growth of human ZR-75-1 breast cancer xenografts., J Natl Cancer Inst source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“An increase of 135% over control (P Ͻ 0.05) in plasma osteocalcin was concomitantly observed, thus suggesting increased bone formation in agreement with our preclinical data (296).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [296] Martel
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Anthropometric measurements showed no change in body weight but a 9.8% decrease in sc skin fold thickness at 12 months (P Ͻ 0.05; Ref. 297).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [297] Diamond, 1996, Metabolic effects of 12-month percutaneous DHEA replacement therapy in postmenopausal women., J Endocrinol
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DHEA administration stimulated vaginal epithelium maturation in 8 of 10 women who had a maturation value of zero at the onset of therapy, whereas a stimulatory effect was also seen in the three women who had an intermediate vaginal maturation before therapy.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The index of sebum secretion was 79% increased after 12 months of DHEA therapy, with a return to pretreatment values 3 months after cessation of treatment.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“the estrogenic stimulatory effect observed in the vagina was not found in the endometrium, which remained completely atrophic in all women after 12 months of DHEA treatment (280).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [280] Labrie, 1997, Effect of 12-month DHEA replacement therapy on bone, vaginum, and endometrium in postmenopausal women., J Clin Endocrinol Metab source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These changes in body fat and muscular surface areas were associated with a 12% decrease (P Ͻ 0.05) of fasting plasma glucose and a 17% decrease (P Ͻ 0.05) in fasting plasma insulin levels.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“serum DHEA and DHEA-S decrease by 50% between the ages of 21 and 40 yr but also that a similar decrease is observed for serum testosterone (26).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Decrease of serum DHEA, androgens, and their metabolites with age
What the sources say
- Not checked yetcites [26] Zumoff, 1995, Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women., J Clin Endocrinol Metab
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such local biosynthesis and action of androgens in target tissues eliminates the exposure of other tissues to androgens and thus minimizes the risks of undesirable masculinizing or other androgen-related side effects.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Decrease of serum DHEA, androgens, and their metabolites with age
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Our best estimate of the intracrine formation of estrogens in peripheral tissues in women is in the order of 75% before menopause and close to 100% after menopause (25).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Structure of the human steroidogenic enzymes
What the sources say
- Not checked yetcites [25] Labrie, 1991, Intracrinology., Mol Cell Endocrinol source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“at 70 yr of age, serum DHEA-S levels are decreased to approximately 20% of their peak values, whereas they can decrease by 95% by the age of 85-90 yr (22).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > A. Intracrinology
What the sources say
- Not checked yetcites [22] Migeon, 1957, Dehydroepiandrosterone and androsterone levels in human plasma. Effect of age and sex: day-to-day and diurnal variations., J Clin Endocrinol Metab source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These steroids are then metabolized in the same cells into inactive glucuronidated and sulfated metabolites, which finally diffuse in the extracellular compartment and can be measured in the circulation.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > C. Women produce about two thirds of the androgens synthesized in men
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“it has been found that Western women having a low excretion of adrenal androgenic metabolites respond more poorly to endocrine therapy and have a shorter survival time (188 -190).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > A. Clinical data
What the sources say
- Not checked yetcites [188] Bulbrook, 1973, Effect of steroidal contraceptives on levels of plasma androgen sulphates and cortisol., Lancet source
- Not checked yetcites [189] Juret, 1968, New biological evidence on the hormone dependence of breast cancer (preliminary note)., Rev Fr Etud Clin Biol
- Not checked yetcites [190] Masnyk, 1978, Prediction of response to adrenalectomy in the treatment of advanced breast cancer., J Natl Cancer Inst source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, the postmenopausal ovary is well known to secrete testosterone, and most authors agree that it also secretes some 4-dione (147, 148).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 3. Contribution of the postmenopausal ovary to serum 4-dione and testosterone.
What the sources say
- Not checked yetcites [147] Judd, 1974, Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood., J Clin Endocrinol Metab source
- Not checked yetcites [148] Longcope, 1980, Steroid secretion by the postmenopausal ovary., Am J Obstet Gynecol source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Peripheral serum testosterone decreases by 50% after ovariectomy in postmenopausal women, thus indicating that the approximately equal contribution of the ovaries and adrenals to serum testosterone remains after menopause.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 3. Contribution of the postmenopausal ovary to serum 4-dione and testosterone.
What the sources say
- Not checked yetcites [158] Judd, 1974, Effect of oophorectomy on circulating testosterone and androstenedione levels in patients with endometrial cancer., Am J Obstet Gynecol source
- Not checked yetcites [159] Maroulis, 1976, Ovarian and adrenal contributions to peripheral steroid levels in postmenopausal women., Obstet Gynecol
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the evidence obtained leaves little doubt that the antiproliferative effect of androgens does not result from competition for binding to the ER, but rather is caused by an AR-mediated mechanism that is additive to blockade of the ER by an antiestrogen.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Preclinical data
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As previously described, MPA is a compound having a complex series of activities, namely progestational, glucocorticoid, and androgenic (231).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
What the sources say
- Not checked yetcites [231] Poulin, 1990, Multiple actions of synthetic “progestins” on the growth of ZR-75-1 human breast cancer cells: an in vitro model for the simultaneous assay of androgen, progestin, estrogen and glucocorticoid agonistic and antagonistic activities of compounds., Breast Cancer Res Treat source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Such data on ER expression provide an explanation for at least part of the antiestrogenic effects of androgens on breast cancer cell growth and provide an explanation for the observations showing that the specific inhibitory effects of androgen therapy are additive to the standard treatment limited to blockade of estrogens by antiestrogens (229).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
What the sources say
- Not checked yetcites [229] de Launoit, 1991, Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells., Cancer Res
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This inhibitory effect of androgens on intracellular ER concentrations may be expected to leave the relative effectiveness of the competitive blockade of estrogen action by antiestrogens unaffected, while decreasing the efficiency of any residual estrogenic stimulation of cell growth.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > of [ 3 H]E 2 (data not shown).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the human adrenals secrete large amounts of the precursor steroids DHEA and DHEA-S, both of which are converted into androgens in target intracrine tissues (25,35,78,92,249,254,255).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [25] Labrie, 1991, Intracrinology., Mol Cell Endocrinol source
- Not checked yetcites [35] Labrie
- Not checked yetcites [78] Labrie, 1988, Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
- Not checked yetcites [92] Labrie, 1997, The key role of 17β-HSDs in sex steroid biology., Steroids source
- Not checked yetcites [249] Labrie, 1989, Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
- Not checked yetcites [254] Labrie, 1996, High bioavailability of DHEA administered percutaneously in the rat., J Endocrinol
- Not checked yetcites [255] Labrie, 1995, DHEA and peripheral androgen and estrogen formation: intracrinology., Ann NY Acad Sci source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the first androgen successfully used in the treatment of advanced breast cancer was testosterone propionate (250).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > IV. DHEA Inhibits Breast Cancer
What the sources say
- Not checked yetcites [250] Nathanson, 1947, Endocrine aspects of human cancer., Recent Prog Res
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Labrie and colleagues (78, 249) first demonstrated that DHEA possesses relatively potent androgenic activity and stimulates androgen-dependent gene expression in the rat ventral prostate.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > IV. DHEA Inhibits Breast Cancer
What the sources say
- Not checked yetcites [78] Labrie, 1988, Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
- Not checked yetcites [249] Labrie, 1989, Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“DHEA can be converted in vivo and in vitro into the weak estrogen 5-diol, which interacts with the ER and can exert weak estrogen-like effects independent from aromatase (253,(267)(268)(269).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites 253,(267)(268)(269)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“human ZR-75-1 breast cancer cells do not express 3-HSD and are thus unable to synthesize androgens, thus explaining the stimulatory effect of DHEA on the growth of these cells under in vitro conditions (253)”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [253] Poulin, 1986, Stimulation of cell proliferation and estrogenic response by adrenal C19-Δ5 -steroids in the ZR-75-1 human breast cancer cell line., Cancer
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“an absence of estrogens does not exist in women where comparable levels of E 2 are found in breast cancer tissue in pre-and postmenopausal women (272).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [272] Poortman, 1983, Subcellular distribution of androgens and oestrogens in target tissue., J Steroid Biochem source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“recent data suggest that progestins exert a negative impact on breast cancer (2-5), with recent reports indicating an increased risk of the disease in women (6,7).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [2] Horwitz, 1992, The molecular biology of RU486. Is there a role for antiprogestins in the treatment of breast cancer?, Endocr Rev
- Not checked yetcites [3] Musgrove, 1991, Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor α, epidermal growth factor receptor, c-fos, and c-myc genes., Mol Cell Biol source
- Not checked yetcites [4] Clarke, 1990, Progestin regulation of cellular proliferation., Endocr Rev source
- Not checked yetcites [5] Colditz, 1995, The use of estrogens and progestins and the risk of breast cancer in postmenopausal women., N Engl J Med source
- Not checked yetcites [6] Ross, 2000, Effect of hormone replacement therapy on breast cancer risk: estrogen vs. estrogen plus progestin., J Natl Cancer Inst source
- Not checked yetcites [7] Magnusson, 1999, Breast-cancer risk following long-term oestrogen- and oestrogen-progestin-replacement therapy., Int J Cancer source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DHEA is well known to be converted into androgens, and treatment with DHEA is known to induce androgen-sensitive gene expression in the rat ventral prostate (78, 249).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [78] Labrie, 1988, Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
- Not checked yetcites [249] Labrie, 1989, Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate., Endocrinology source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“by itself, DHEA does not possess any significant androgenic or estrogenic activity, its activity being dependent upon its transformation into androgens and/or estrogens in peripheral target intracrine tissues (25).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [25] Labrie, 1991, Intracrinology., Mol Cell Endocrinol source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DHEA, secondary to its predominant transformation into androgens in mammary gland tissue, exerts an inhibitory effect on mammary carcinoma development and growth, an effect that counteracts and can even completely neutralize the stimulatory effect of estrogens.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is likely that endogenous androgens and DHEA play an important physiological role in the control of normal breast tissue growth and function and that this antagonism between androgens and estrogens is also operative in breast cancer.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A group of researchers have reported that DHEA is inhibitory on breast cancer growth in the presence of estrogens, whereas it can be stimulatory on experimental models in which estrogens are absent (197,270).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > 2. Inhibitory effect of DHEA on breast cancer
What the sources say
- Not checked yetcites [197] Secreto, 1991, Serum and urinary androgens and risk of breast cancer in postmenopausal women., Cancer Res
- Not checked yetcites [270] Boccuzzi, 1992, Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas., Anticancer Res
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“all these benefits, including improved libido, have been obtained without significant side effect (73, 74).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [73] Baulieu, 2000, Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue., Proc Natl Acad Sci USA source
- Not checked yetcites [74] Stomati, 2000, Six-months oral dehydroepiandrosterone supplementation in early and late postmenopause., Gynecol Endocrinol source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The 70 -95% reduction in the formation of DHEA and DHEA-S by the adrenals during aging results in a dramatic reduction in the formation of androgens and estrogens in peripheral target tissues, which could well be involved in the pathogenesis of age-related diseases such as insulin resistance (307, 308) and obesity (309 -311).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [307] Schriock, 1988, Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding., J Clin Endocrinol Metab source
- Not checked yetcites [308] Coleman, 1982, Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice., Diabetes source
- Not checked yetcites [309] Nestler, 1988, Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men., J Clin Endocrinol Metab source
- Not checked yetcites [310] MacEwen, 1991, Obesity in the dog: role of the adrenal steroid dehydroepiandrosterone (DHEA)., J Nutr source
- Not checked yetcites [311] Tchernof, 1995, Reduced testosterone and adrenal C19 steroid levels in obese men., Metabolism source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DHEA has been shown to have immunomodulatory effects in vitro (313) and in vivo in fungal and viral diseases (314), including HIV (315), and a stimulatory effect of DHEA on the immune system has been described in postmenopausal women (316).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [313] Suzuki, 1991, Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells., Clin Immunol Immunopathol source
- Not checked yetcites [314] Rasmussen, 1992, Effectiveness of dehydroepiandrosterone in reduction of cryptosporidial activity in immunosuppressed rats., Antimicrob Agents Chemother source
- Not checked yetcites [315] Henderson, 1992, Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication., AIDS Res Hum Retroviruses source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“DHEA replacement in Addison's disease is associated with an improvement in psychological well-being, mood, and fatigue (70).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [70] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Testosterone administration to elderly men increases the fractional synthetic rate of muscle protein as well as muscle strength (320).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [320] Urban, 1995, Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis., Am J Physiol
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the 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.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > V. Rationale for the Use of DHEA as a Source of Androgens in Postmenopausal Women
What the sources say
- Not checked yetcites [23] Labrie, 1997, Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging., J Clin Endocrinol Metab source
- Not checked yetcites [25] Labrie, 1991, Intracrinology., Mol Cell Endocrinol source
- Not checked yetcites [27] Labrie, 1997, Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology., J Clin Endocrinol Metab source
- Not checked yetcites [33] Labrie, 2000, Intracrinology: role of the family of 17β-hydroxysteroid dehydrogenases in human physiology and disease., J Mol Endocrinol source
- Not checked yetcites [84] Labrie, 1992, Structure, function and tissue-specific gene expression of 3β-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase enzymes in classical and peripheral intracrine steroidogenic tissues., J Steroid Biochem Mol Biol source
- Not checked yetcites [86] Labrie, 1995, The human type II 17β-hydroxysteroid dehydrogenase gene encodes two alternatively-spliced messenger RNA species., DNA Cell Biol source
- Not checked yetcites [90] Labrie, 1994, Structure, regulation and role of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and aromatase enzymes in formation of sex steroids in classical and peripheral intracrine tissues., Baillière’s Clin Endocrinol Metab source
- Not checked yetcites [92] Labrie, 1997, The key role of 17β-HSDs in sex steroid biology., Steroids source
- Not checked yetcites [261] Labrie, 1992, Structure and tissue-specific expression of 3β-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues., J Steroid Biochem Mol Biol source
- Not checked yetcites [280] Labrie, 1997, Effect of 12-month DHEA replacement therapy on bone, vaginum, and endometrium in postmenopausal women., J Clin Endocrinol Metab source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The use of ERT requires the addition of progestins to counteract the endometrial proliferation induced by estrogens, whereas both estrogens and progestins could increase the risk of breast cancer (5,318).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [5] Colditz, 1995, The use of estrogens and progestins and the risk of breast cancer in postmenopausal women., N Engl J Med source
- Not checked yetcites [318] Bardon, 1985, RU486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor., J Clin Endocrinol Metab source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observed stimulatory effect of DHEA on bone mineral density and the increase in serum osteocalcin, a marker of bone formation, are of particular interest for the prevention and treatment of osteoporosis and indicate a unique activity of DHEA on bone physiology, namely a stimulation of bone formation, whereas ERT and HRT can only reduce the rate of bone loss.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at physiological replacement doses, DHEA does not stimulate the endometrium, thus removing the need to use a progestin to counteract the stimulation of the endometrium by estrogen.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although bone formation, inhibition of mammary gland proliferation, stimulation of sebaceous glands, muscle mass increase, and improved libido are attributed to the formation of androgens in the corresponding target tissues, the decreased insulin resistance and vaginal maturation are best explained by the local formation of estrogens.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The absence of stimulation of the endometrium by DHEA eliminates the need for progestin replacement therapy, thus avoiding the fear of progestininduced breast cancer added to the well known stimulatory effect of estrogens.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A significant improvement in mood and well-being was observed in patients with major depression (331) and midlife asthenia (332), whereas no effect was detected in perimenopausal women (333).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [331] Wolkowitz, 1999, Double-blind treatment of major depression with dehydroepiandrosterone., Am J Psychiatry source
- Not checked yetcites [332] Bloch, 1999, Dehydroepiandrosterone treatment of midlife dysthymia., Biol Psychiatry source
- Not checked yetcites [333] Barnhart, 1999, The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life., J Clin Endocrinol Metab
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, at physiological replacement doses, DHEA has been found in clinical studies to induce a series of beneficial effects closely associated with the protection of women's health, whereas no negative effects have been observed.”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Findings from the animal models and cell lines used in the paper are predictive of DHEA's effects on breast cancer and other outcomes in women.
None of the sources cited for this claim have been checked yet.
In the paper
“scores of activity of daily living were improved by DHEA in patients with myotonic dystrophy (329), whereas no change was observed in healthy elderly men (330).”
§ Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone > B. Benefits of DHEA in postmenopausal women
What the sources say
- Not checked yetcites [329] Sugino, 1998, A pilot study of dehydroepiandrosterone sulfate in myotonic dystrophy., Neurology source
- Not checked yetcites [330] Flynn, 1999, Dehydroepiandrosterone replacement in aging humans., J Clin Endocrinol Metab
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The sum of serum concentrations of ADT-G, 3α-diol-G, and 3β-diol-G reflects relative total androgen production in men and women despite possible differences in metabolic clearance rates.
“Although the metabolic clearance rates of the three main androgen metabolites are likely to show differences between men and women, 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 (”
The paper relies on this without support.
Findings from the animal models and cell lines used in the paper are predictive of DHEA's effects on breast cancer and other outcomes in women.
“Such data also suggest a potential use of DHEA as a physiological approach for the prevention of breast cancer in women.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The remaining 50% originates from the peripheral conversion of androgen precursors such as A4 to testosterone [[276], [277], [278]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [276]
In the citing paper
“Breast cancer tissue has STS, 3βHSD, reductive 17βHSD, 5α-reductase and aromatase activities (Labrie et al., 2003, McNamara and Sasano, 2015b, Suzuki et al., 2005) as well as 3αHSD, UGT, and SULT activity (McNamara et al., 2013).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Labrie et al., 2003
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Type 2 17-HSD is described as both oxidative and reductive
MinorThe paper classifies type 2 17-HSD as catalyzing an oxidative reaction, but later attributes a reductive action to the same enzyme.
“This enzyme inactivates the estrogens and androgens made after the reductive action of type 2, 3, and 5 17-HSDs.”
“These findings agree with the isolation of multiple types of 17-HSDs in which approximately half catalyze the reductive reaction ( types 1, 3, 5, and 7) and half catalyze the oxidative reaction (types 2, 4, 6, and 8).”
DHEA is called the only sex-steroid source despite E 1 supplementation
MinorThe statement that exogenous DHEA is the only source of sex steroids in the ovariectomized mice conflicts with the description of the DHEA-treated mice as supplemented with E 1.
“In the ovariectomized mouse, exogenous DHEA represents the only source of sex steroids in peripheral tissues, including the mammary gland.”
“On the other hand, treatment with increasing doses of percutaneous DHEA caused a progressive inhibition of E 1 -stimulated ZR-75-1 tumor growth.”
Citations
Cites
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Flagged first, then by citations
51 of the 388 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
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Cited by
Sorted by citations
Items 401–500 of 545
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“Although circulating androstenedione derives from the ovaries and adrenal glands, most of the androstenedione found in androgen-sensitive tissues originates from the intracellular conversion of DHEAS and DHEA to androstenedione [9,20].”
BackgroundInfluentialSexual Function in Postmenopausal Women and Serum Androgens: A Review Article
Nazarpour, S., Simbar, M., & Tehrani, F. R. (2019) · International Journal of Sexual Health · doi:10.1080/19317611.2019.1622617 · Cited by 6
“There is also contradictory evidence on the effectiveness of DHEA in improving sexual function (Labrie et al., 2003).”
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“Although a positive relationship between DHEA-S and the risk of breast cancer has been suggested [35], possibly through an estrogenic effect of its major metabolite, 5-androstenediol [36], androgens have clearly demonstrated to inhibit the growth of human breast cancer in several studies in vivo and in vitro [37].”
Pham, K. T. N., Miyake, T., Suzuki, T., Kinoshita, S., Hamada, Y., Uehara, H., Machida, M., Nakajima, T., Hasegawa, E., & Doi, M. (2025) · iScience · doi:10.1016/j.isci.2025.111808 · Cited by 8
“…in the tissue where they exert their effect without release into circulation, has been described 1–3 for a number of extra-gonadal tissues such as uterine endometrium 4–6 and skin sebaceous gland 7,8 as well as several cancerous tissues including those of the prostate, 9,10 breast, 11,12 and bone.”
Hietala, M., Henningson, M., Törngren, T., Olsson, H. L., & Jernström, H. (2010) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2010.09.006 · Cited by 5
“Approximately 25% of testosterone in women is produced in the ovaries, 25% in the adrenal glands and 50% via conversion of the proandrogens dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione in the peripheral tissues [4, 5].”
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“…androgen-dependent tissues from healthy humans and also from patients with different diseases [English et al., 2000; Kim et al., 2002; Provost et al., 2002; Blouin et al., 2003; Labrie et al., 2003; Oduwole et al., 2003; Oliveira et al., 2003; Quinkler et al., 2003, 2004; Stoffel-Wagner, 2003].”
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“30 In women, synthesis of testosterone in peripheral tissues accounts for a significant proportion of total testosterone production: It is estimated that only 10%–15% of testosterone diffuses from these tissues into the circulation without prior metabolism to the more biologically active DHT. 31 DHT is inactivated in a…”
InfluentialCirculating steroid levels as correlates of adipose tissue phenotype in premenopausal women
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“This is an op a b s t r a c t a r t i c l e i n f o Article history: Received 24 October 2016 Accepted 10 January 2017 Available online xxxx Context: Sulfate is critical in the biotransformation of multiple compounds via sulfation.”
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“The plasma levels of DHEA and DHEAS decrease with aging in both men and women (Labrie et al., 2003).”
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“Dans la prostate, la DHT constitue aussi un substrat pour plusieurs enzymes qui catalysent des réactions réversibles comme la 17β-hydroxystéroïde déhydrogénase (17β-HSD) et la 3α-hydroxystéroïde déhydrogénase (3α-HSD) qui produisent l’androstérone et l’androstane-3α,17β-diol (3α-diol) (Figure 1) [5].”
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“In postmenopausal women, circulating estrogen concentrations are lower when compared to premenopausal levels, contributing to a relative increase in androgenic concentrations.(34) More specifically, androgen production decreases over the lifespan, including after menopause.”
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Metadata
- Authors
- Labrie, F., Luu-The, V., Labrie, C., Bélanger, A., Simard, J., Lin, S.-X., & Pelletier, G.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (Centre Hospitalier de l’Université Laval) and Laval University, Québec City, Québec G1V 4G2, Canada
- Corresponding author
- Labrie, Fernand
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2003-04-01
- Volume
- 24
- Issue
- 2
- Pages
- 152-182
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2145801998
- Semantic Scholar
- 5f3da77db259eaf579a8b039f88e7736457e19f2
- Cited by
- 544
- References
- 388
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 32 · 2021: 17 · 2020: 11 · 2019: 14 · 2018: 20 · 2017: 16 · 2016: 24 · 2015: 18 · 2014: 26 · 2013: 19 · 2012: 22
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Université Laval
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- dehydroepiandrosterone, DHEA sulfate, intracrinology, menopause, hormone replacement therapy, breast cancer prevention, bone mineral density, bone formation, androgen receptor, aromatase, 17β-hydroxysteroid dehydrogenase
- MeSH terms
- Adult, Aged, Aged, 80 and over, Androgens, Animals, Breast Neoplasms, Dehydroepiandrosterone, Female, Humans, Menopause, Middle Aged, 17-Hydroxysteroid Dehydrogenases, Bone Density
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