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Anabolic Steroids
Is DHEA suppressive?
- Thread starter Tyler81
- Start date
mich29
New Member
if I remember correctly if used for a long period of time yes it can be suppressive depending on your dosing use
I am unable to find the reference on DHEA supplementation and T. It would be necessary to administer large DHEA doses to appreciably change the T level and effect the HPTA. Even androstenedione did not change the T level much. I would be very surprised to see any negative HPTA effect.
It may not be suppressive, but it is worthless....
As you mentioned, and I think I once read in an article associated with Bill Roberts (The Master of prohormones today). It stated some 1% conversion of androstenedial (spelling
), and about a 5% conversion rate with the one you mentioned (androstenedione). I think the article was discussing 1-testosterone.
Obviously DHEA is a precursor to both of these at best, so yes, do the math and you should come up with a pretty big GOOSE EGG in terms of production. The real question would be WHAT are you lacking, and HOW could DHEA supp'ing be uptaked. There is no question that I get some kind of kick from DHEA, but only for a few weeks. And then all is either balanced and I discount, or everthing equalizes back to where it was. Either way I loose the motivation to keep taking.
Two things: Strangely I have massive acne outbreaks during the 3 week periods I have seen results from DHEA. Second, clearly studies suggest that DHEA has a pretty strong affinity to convert to estrogens for whatever reason.... So I cant explain the first in my case....
As you mentioned, and I think I once read in an article associated with Bill Roberts (The Master of prohormones
today). It stated some 1% conversion of androstenedial (spelling), and about a 5% conversion rate with the one you mentioned (androstenedione). I think the article was discussing 1-testosterone.Obviously DHEA is a precursor to both of these at best, so yes, do the math and you should come up with a pretty big GOOSE EGG in terms of production. The real question would be WHAT are you lacking, and HOW could DHEA supp'ing be uptaked. There is no question that I get some kind of kick from DHEA, but only for a few weeks. And then all is either balanced and I discount, or everthing equalizes back to where it was. Either way I loose the motivation to keep taking.
Two things: Strangely I have massive acne outbreaks during the 3 week periods I have seen results from DHEA. Second, clearly studies suggest that DHEA has a pretty strong affinity to convert to estrogens for whatever reason.... So I cant explain the first in my case....
Thanks for your reply
So only large doses of DHEA may supress Testosterone/HPTA?
Bullshit! It elevates E2!
Really?
Care to provide any evidence? ANY!!! DHEA Is not HPTA suppressive to ANY (IF AT ALL) significant effect.
Labrie F, Belanger A, Cusan L, Candas B. Physiological Changes in Dehydroepiandrosterone Are Not Reflected by Serum Levels of Active Androgens and Estrogens But of Their Metabolites: Intracrinology. J Clin Endocrinol Metab 1997;82(8):2403-9. http://jcem.endojournals.org/cgi/content/full/82/8/2403
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 ([~]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.
Gurnell EM, Hunt PJ, Curran SE, et al. Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial. J Clin Endocrinol Metab 2008;93(2):400-9. http://jcem.endojournals.org/cgi/content/full/93/2/400
Context: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected.
Objective and Design: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison's disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue.
Results: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects.
Conclusion: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison's disease.
Last edited:
Komesaroff PA. Unravelling the Enigma of Dehydroepiandrosterone: Moving Forward Step by Step. Endocrinology 2008;149(3):886-8. Unravelling the Enigma of Dehydroepiandrosterone: Moving Forward Step by Step -- Komesaroff 149 (3): 886 -- Endocrinology
Dehydroepiandrosterone (DHEA) is a controversial hormone. There is debate about its physiological roles, its mechanisms of action, its relationships to health and disease, indeed, whether it is a hormone at all (1, 2). Despite uncertainty about its status, it is widely promoted and sold as a complementary medicine. Even here, there are controversies and discrepancies: whereas in the United States it is freely available as a harmless health food, in Australia and elsewhere it is regarded as an anabolicsteroid and its distribution is strictly controlled. In the midst of this uncertainty the article by Liu et al. (3) in this issue contributes important new evidence about the physiological actions of DHEA and the intracellular signaling pathways by which they are controlled.
DHEA and its sulfated prohormone, DHEA sulfate (DHEAS) are quantitatively the most abundant circulating adrenal steroid hormones in humans. Circulating DHEAS serves as a reservoir for DHEA, with conversion by sulfotransferases occurring in a wide range of tissues. There is also extensive metabolism to estrogens and androgens, giving rise to the view that many of its effects are mediated by these hormones or other metabolites (4). Plasma DHEAS levels decline with age and vary with sex, ethnicity, and environmental factors (5).
DHEA has been linked, usually controversially, to many diseases, including malignancies (6), neurological dysfunction (7), and systemic lupus erythematosus and other immune disorders (8), and claims have been made that DHEA deficiency contributes to the symptoms associated with adrenal insufficiency (9), ageing (10, 11), menopause (12), and disorders of sexual function (13). However, the major interest in the hormone stems from epidemiological studies that have been said to show an inverse relationship between cardiovascular mortality and plasma DHEA(S) levels in men (14). Although these data too are hotly contested (15, 16), over the last few years, evidence has steadily mounted in support of a physiological role for DHEA in cardiovascular tissues.
Animal studies have shown anti-atherogenic actions in several models of vascular dysfunction (17, 18, 19). In vitro data have shown actions on vascular endothelium and smooth muscle (20, 21, 22, 23) and on key mediators of atherogenesis. DHEA(S) influences proliferation of vascular endothelial cells and smooth muscle cells independently of androgen and estrogen receptors (22, 23, 24). In endothelial cells, it increases expression of nitric oxide synthase (NOS) and thereby secretion of NO, an important regulator of vascular function, and protects these cells against apoptosis (25, 26). DHEA administration to humans improves vascular endothelial function (22, 27), reduces known cardiovascular risk markers (28, 29), and appears to inhibit atherosclerosis (17, 18, 19). The effects on endothelial cells are mediated, at least in part, through the activation of the MAPK ERK1/2 (22, 30).
Progress has been made in elucidating the receptors through which DHEA acts. Although the best characterized steroid receptors are nuclear transcription factors, it is now recognized that steroids can in some cases also activate plasma membrane receptors and thereby initiate cytosolic kinase cascades (26, 31, 32, 33). In fact, in a landmark paper in 2002, Liu et al. (34) reported a membrane-bound, G protein-coupled receptor for DHEA identified in bovine vascular endothelial cells. The binding of ligand was of high affinity (Kd = 48.7 pM) and saturable. These authors have since shown that the receptor is maximally activated by 1–10 nM DHEA to stimulate endothelial NOS and enhance NO production (35).
In separate studies, it has been shown that the release of NO depends on activation of ERK1/2 (26). Activation of ERK1/2 is a crucial signaling event in a number of cellular functions, including proliferation, migration, cell growth, angiogenesis, survival, and apoptosis (36). In vascular endothelial cells, ERK1/2 contributes to stimulation of endothelial NOS and is activated in response to a range of extracellular stimuli, including growth factors, estrogens, shear stress (37, 38), and DHEA (39).
In their current study, Liu et al. (3) put these various insights together to show that the effect of DHEA on endothelium occurs via activation of ERK1/2. They provide evidence linking DHEA effects at the endothelial plasma membrane with cellular proliferation and angiogenesis by a process mediated by pertussis toxin-sensitive G proteins and ERK1/2. In these experiments, pertussis toxin completely blocked DHEA-induced ERK1/2 activation, endothelial cell proliferation and migration, and vascular tube formation, suggesting that Gi proteins link DHEA effects with the endothelial cell processes. The authors also show rapid nuclear translocation of activated ERK1/2, a critical step in the transcriptional and cell proliferative effects of this kinase.
As a result of the work of Liu et al. (3) and others, we can now confidently accept that DHEA(S) is biologically active in its own right in cardiovascular tissue, acts through specific, membrane-bound, G protein-coupled, receptors, increases production of NOS and NO, and contributes to intracellular signaling through activation of ERK1/2 and other messengers.
This is a significant achievement. However, it leaves many questions still to be answered. Uncertainty remains about the control of the biological events, given the high circulating concentrations of DHEA. As the authors themselves point out, based on in vitro pharmacokinetic studies, human plasma concentrations of DHEA are such that the putative receptor would be fully saturated. It is possible that the specificity of DHEA action is established through control of hormone delivery to tissues by yet to be characterized binding proteins, tissue-specific DHEA receptor expression, regulation of the expression and activity of the receptor, expression of coreceptors, or other mechanisms.
Whether the receptor mechanism elaborated here is either necessary or sufficient to explain the cellular effects of DHEA remains to be determined. The time courses and dose-response characteristics of the effects of the hormone in these experiments and those from other laboratories vary widely, suggesting that the actions may occur via more than one receptor and effector pathway. It is known that DHEA and its metabolites can activate estrogen receptors (especially estrogen receptor-?), the peroxisome proliferators-activated receptor- , and the pregnane X receptor, and the existence of several other membrane-associated receptors has also been suggested (40). It is even possible that a specific nuclear receptor will be identified that mediates actions via other transcription factors to regulate cell proliferation, in addition to the plasma membrane-initiated kinase signaling effects.
The full range of biologically active forms of DHEA remain to be elucidated. DHEA is metabolized intracellularly to other steroids, including estradiol, which also induces vascular endothelial proliferation by activation of MAPKs (41, 42), androstenediol (43), and other substances. It is possible that complex actions are mediated through different metabolites and different receptors, including differential effects on estrogen receptor- and -?.
Most importantly, how these data translate into clinical outcomes remains to be determined. Whether DHEA is a key player in cardiovascular disease, whether deficiencies or excesses are beneficial or harmful, whether administration or withholding of the hormones is appropriate in defined clinical settings—all of these questions remain to be answered. However, what we can say is that the time is at last approaching when we will be able to design the studies to address them.
In conclusion, the new science of DHEA has yielded important knowledge about this enigmatic hormone and its actions. We have come a long way, but there is still a long way to go before we can feel confident that we understand its physiological and therapeutic roles.
Labrie F, Luu-The V, Belanger A, et al. Is dehydroepiandrosterone a hormone? J Endocrinol 2005;187(2):169-96. Is dehydroepiandrosterone a hormone? -- Labrie et al. 187 (2): 169 -- Journal of Endocrinology
Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.
Dehydroepiandrosterone (DHEA) is a controversial hormone. There is debate about its physiological roles, its mechanisms of action, its relationships to health and disease, indeed, whether it is a hormone at all (1, 2). Despite uncertainty about its status, it is widely promoted and sold as a complementary medicine. Even here, there are controversies and discrepancies: whereas in the United States it is freely available as a harmless health food, in Australia and elsewhere it is regarded as an anabolicsteroid and its distribution is strictly controlled. In the midst of this uncertainty the article by Liu et al. (3) in this issue contributes important new evidence about the physiological actions of DHEA and the intracellular signaling pathways by which they are controlled.
DHEA and its sulfated prohormone, DHEA sulfate (DHEAS) are quantitatively the most abundant circulating adrenal steroid hormones in humans. Circulating DHEAS serves as a reservoir for DHEA, with conversion by sulfotransferases occurring in a wide range of tissues. There is also extensive metabolism to estrogens and androgens, giving rise to the view that many of its effects are mediated by these hormones or other metabolites (4). Plasma DHEAS levels decline with age and vary with sex, ethnicity, and environmental factors (5).
DHEA has been linked, usually controversially, to many diseases, including malignancies (6), neurological dysfunction (7), and systemic lupus erythematosus and other immune disorders (8), and claims have been made that DHEA deficiency contributes to the symptoms associated with adrenal insufficiency (9), ageing (10, 11), menopause (12), and disorders of sexual function (13). However, the major interest in the hormone stems from epidemiological studies that have been said to show an inverse relationship between cardiovascular mortality and plasma DHEA(S) levels in men (14). Although these data too are hotly contested (15, 16), over the last few years, evidence has steadily mounted in support of a physiological role for DHEA in cardiovascular tissues.
Animal studies have shown anti-atherogenic actions in several models of vascular dysfunction (17, 18, 19). In vitro data have shown actions on vascular endothelium and smooth muscle (20, 21, 22, 23) and on key mediators of atherogenesis. DHEA(S) influences proliferation of vascular endothelial cells and smooth muscle cells independently of androgen and estrogen receptors (22, 23, 24). In endothelial cells, it increases expression of nitric oxide synthase (NOS) and thereby secretion of NO, an important regulator of vascular function, and protects these cells against apoptosis (25, 26). DHEA administration to humans improves vascular endothelial function (22, 27), reduces known cardiovascular risk markers (28, 29), and appears to inhibit atherosclerosis (17, 18, 19). The effects on endothelial cells are mediated, at least in part, through the activation of the MAPK ERK1/2 (22, 30).
Progress has been made in elucidating the receptors through which DHEA acts. Although the best characterized steroid receptors are nuclear transcription factors, it is now recognized that steroids can in some cases also activate plasma membrane receptors and thereby initiate cytosolic kinase cascades (26, 31, 32, 33). In fact, in a landmark paper in 2002, Liu et al. (34) reported a membrane-bound, G protein-coupled receptor for DHEA identified in bovine vascular endothelial cells. The binding of ligand was of high affinity (Kd = 48.7 pM) and saturable. These authors have since shown that the receptor is maximally activated by 1–10 nM DHEA to stimulate endothelial NOS and enhance NO production (35).
In separate studies, it has been shown that the release of NO depends on activation of ERK1/2 (26). Activation of ERK1/2 is a crucial signaling event in a number of cellular functions, including proliferation, migration, cell growth, angiogenesis, survival, and apoptosis (36). In vascular endothelial cells, ERK1/2 contributes to stimulation of endothelial NOS and is activated in response to a range of extracellular stimuli, including growth factors, estrogens, shear stress (37, 38), and DHEA (39).
In their current study, Liu et al. (3) put these various insights together to show that the effect of DHEA on endothelium occurs via activation of ERK1/2. They provide evidence linking DHEA effects at the endothelial plasma membrane with cellular proliferation and angiogenesis by a process mediated by pertussis toxin-sensitive G proteins and ERK1/2. In these experiments, pertussis toxin completely blocked DHEA-induced ERK1/2 activation, endothelial cell proliferation and migration, and vascular tube formation, suggesting that Gi proteins link DHEA effects with the endothelial cell processes. The authors also show rapid nuclear translocation of activated ERK1/2, a critical step in the transcriptional and cell proliferative effects of this kinase.
As a result of the work of Liu et al. (3) and others, we can now confidently accept that DHEA(S) is biologically active in its own right in cardiovascular tissue, acts through specific, membrane-bound, G protein-coupled, receptors, increases production of NOS and NO, and contributes to intracellular signaling through activation of ERK1/2 and other messengers.
This is a significant achievement. However, it leaves many questions still to be answered. Uncertainty remains about the control of the biological events, given the high circulating concentrations of DHEA. As the authors themselves point out, based on in vitro pharmacokinetic studies, human plasma concentrations of DHEA are such that the putative receptor would be fully saturated. It is possible that the specificity of DHEA action is established through control of hormone delivery to tissues by yet to be characterized binding proteins, tissue-specific DHEA receptor expression, regulation of the expression and activity of the receptor, expression of coreceptors, or other mechanisms.
Whether the receptor mechanism elaborated here is either necessary or sufficient to explain the cellular effects of DHEA remains to be determined. The time courses and dose-response characteristics of the effects of the hormone in these experiments and those from other laboratories vary widely, suggesting that the actions may occur via more than one receptor and effector pathway. It is known that DHEA and its metabolites can activate estrogen receptors (especially estrogen receptor-?), the peroxisome proliferators-activated receptor- , and the pregnane X receptor, and the existence of several other membrane-associated receptors has also been suggested (40). It is even possible that a specific nuclear receptor will be identified that mediates actions via other transcription factors to regulate cell proliferation, in addition to the plasma membrane-initiated kinase signaling effects.
The full range of biologically active forms of DHEA remain to be elucidated. DHEA is metabolized intracellularly to other steroids, including estradiol, which also induces vascular endothelial proliferation by activation of MAPKs (41, 42), androstenediol (43), and other substances. It is possible that complex actions are mediated through different metabolites and different receptors, including differential effects on estrogen receptor- and -?.
Most importantly, how these data translate into clinical outcomes remains to be determined. Whether DHEA is a key player in cardiovascular disease, whether deficiencies or excesses are beneficial or harmful, whether administration or withholding of the hormones is appropriate in defined clinical settings—all of these questions remain to be answered. However, what we can say is that the time is at last approaching when we will be able to design the studies to address them.
In conclusion, the new science of DHEA has yielded important knowledge about this enigmatic hormone and its actions. We have come a long way, but there is still a long way to go before we can feel confident that we understand its physiological and therapeutic roles.
Labrie F, Luu-The V, Belanger A, et al. Is dehydroepiandrosterone a hormone? J Endocrinol 2005;187(2):169-96. Is dehydroepiandrosterone a hormone? -- Labrie et al. 187 (2): 169 -- Journal of Endocrinology
Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause.
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