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Even Minor Stress Substantially Decreases DHEA-S Levels

Discussion in 'Scientific Studies' started by haidut, Dec 9, 2016.

  1. haidut

    haidut Member

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    Most endocrinologists are at a loss when asked what leads to lower DHEA-S levels. The generic response is "aging" but the DHEA-S have been steadily declining over the last 30 years (just as testosterone) in young people, so that explanation does not add up. While Peat has not directly written about it, DHEA and DHEA-S seem to be the primary antagonists to cortisol and their levels go up under stress but eventually decline if the stress becomes chronic. This study found that even a brief, and relatively minor in magnitude, stress episode can decrease DHEA-S levels by 35%+ and the decline can persist for many hours after the stressor is gone. What is more important, the decline magnitude was similar to the decline induced by a much larger stressor, so even "minor" stress in your life has detrimental effects on your health. DHEA-S levels are one of the best predictors of overall health, reduced all-cause mortality, and longevity and as such keeping its levels from dropping is quite important.

    Decrease of DHEA-S concentration succeeding a micro-dose thumb exertion: mood-state determinants reflect stress-biomarker responses

    "...The primary finding of the present study was that a serological decrease in DHEA-S concentration occurs within 60-min succeeding a micro-dose of resisted thumb-exertion in untrained participants. This decrease is believed to represent physiological consumption for stress compensation (Lee et al. 2006; Gudemez et al. 2002) and this notion was supported by the unique changes observed in mood-state determinants, tension and fatigue, relative to the physical aptitude of participants in the present study. Additionally, the magnitude of change in DHEA-S matched previous reports for male subjects under much larger-dose conditions (Chen et al. 2011; Liao et al. 2012). These are highly novel observations considering the minimal dose of exercise employed, and the acute time-course in which changes occurred (Lee et al. 2006; Liao et al. 2012; Tsai et al. 2006). Importantly, the present study utilised a highly-standardised exercise-intervention (Mathiowetz et al. 1985; Punsola-Izard et al. 2012) which controlled for potential inter-individual differences in biomechanics. The present findings therefore validate and expand upon existing data on DHEA-S responses to exercise which were obtained through high-dose, multiple-joint exercise protocols (Chen et al. 2011; Lee et al. 2006; Liao et al. 2012; Tsai et al. 2006)."
     
  2. mirc12354

    mirc12354 Member

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    Very intersting, my DHEA-S is usually in the lower 30 % of the range altough my prolactin is low (under 5) and TSH low as well (under 1) and cholesterol also low. Cortisol is usually high (but within range). I was just wondering what does this mean - so high cortisol (high stress) and consequently rather low DHEA-S but at the same time low prolactin (so low stress? - prolactin as some general measurement of the stress the body is under)? BTW: My total testosterone is in the upper half of range and progesterone on the higher limit of range.
     
  3. OP
    haidut

    haidut Member

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    DHEA-S and cortisol are usually inversely correlated. Since cortisol stimulates aromatase and thus estrogen synthesis, some studies claim that there is a negative feedback mechanism where estrogen lowers DHEA-S production as under stress it would lead to more estrogen synthesis. Given that your T levels are good you are probably protected from the effects of stress more or less, but if you managed to get cortisol levels to drop a bit the DHEA-S levels should rebound.
     
  4. Wagner83

    Wagner83 Member

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    This was from a back and forth between me and haidut:

    Me:
    I found something interesting about physiological doses of hormones, the whole paper may be interesting:

    "
    The 10-mg dose of fluoxymesterone that was used is equivalent to 7 to 8 mg of testosterone and thus only slightly exceeds the average testosterone production rate (21). Yet this dose resulted in a 50% reduction in plasma testosterone. [...] Stimulation with either ACTH or HCG intramuscularly causes
    increases in plasma cortisol or testosterone within a few hours, and chronic stimulation with smaller doses of each tropic hormone leads to a slower rise in the respective plasma steroid levels. Similarly, doses of corticoid or androgen in the physiologic range cause an approximate 50% decrease
    in the secretion of cortisol or testosterone, and this inhibition can be extended by the use of large amounts of corticoid or androgen. The physiologic significance of the capacity of the Leydig cell to respond acutely to the level of interstitial cell stimulating hormone remains to be defined."

    haidut:

    The last study is also interesting because if shows prednisone tanked DHEA levels by more than 67% and they said the 20mg administered prednisone is not even close to a suppressive dose for adrenals. So, this directly explains away the idea of "pregnenolone steal" that some people promote so much - i.e. any time there is a rize of cortisol there will be a drop in DHEA and there is no "steal" required. Cortisol simply suppressed DHEA synthesis directly (possibly through ACTH) and also over time atrophies the adrenal zone that produces DHEA.
    "...Effect of ACTH and prednisone. The effects of stimulation and suppression of the adrenal cortex are presented in Table VII. Prednisone caused an irregular decrease in plasma testosterone levels averaging 21% with four of the six subjects demonstrating this decrease. The effects of ACTH stimulation were less conclusive, and only two of the four subjects had a higher plasma testosterone level after stimulation. By contrast prednisone caused a 69% decrease in plasma dehydroepiandrosterone levels, and ACTH produced large increases in two of four subjects."



     
  5. jb116

    jb116 Member

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    Isn't high DHEA-S found in Alzheimer's though? Any in sight on that?
     
  6. OP
    haidut

    haidut Member

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    Could be an adaptive change. I asked Peat about this and he said he thinks in low doses DHEA is strongly protective against AD.
     
  7. jb116

    jb116 Member

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    Ah so, just like cholesterol then :cool:
     
  8. Wagner83

    Wagner83 Member

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    I don't know squat about biology etc.. but thought those could interest other members.

    Plasma dehydroepiandrosterone-sulphate is related to personality and stress response. - PubMed - NCBI
    CONCLUSIONS: DHEAS may be a protective factor against an excessive cortisol response when people are under stress situations. Personality may be related to DHEAS reactivity.

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) and emotional processing — A behavioral and electrophysiological approach - ScienceDirect

    The present results also highlight the relevance of the balance between DHEA, DHEAS and cortisol concerning the processing of negative emotions. Importantly, these results agree with findings at the clinical level, in which higher DHEAS concentrations and DHEA-to-cortisol ratios but not DHEA levels alone were related to less frequent depression, less depressive mood and higher well-being scores (Barrett-Connor et al., 1999; Michael et al., 2000; Young et al., 2002). Although DHEA and DHEAS can be converted into each other and general common effects are expected for the sulfated and non-sulfated form of the hormone (Baulieu and Robel, 1998; Dong and Zheng, 2011; Maninger et al., 2009), several differences exist in their mechanism of action. For instance, DHEAS has a much more potent excitatory action by NMDA agonism and gabaminergic antagonism than DHEA, which may account for some differential effects (Baulieu and Robel, 1998; Imamura and Prasad, 1998; Monnet et al., 1995). Moreover, as stated, sulfated steroids in general possibly act as endogenous neuromodulators (Gibbs et al., 2006) and the balance between DHEAS and DHEA might influence brain functioning. Previous studies at the cellular and molecular level showed that DHEAS had neuroprotective effects mediated through GABA-A receptor antagonism (Majewska, 1992), DHEAS stimulated dopamine release from rat hypothalamic cells (Murray and Gillies, 1997) and DHEAS antagonized the neurotoxic effect of high doses of DHEA (Gil-ad et al., 2001). These studies suggest potential mechanisms by which DHEAS could have more potent anti-depressant effects than DHEA and agree with the present finding that higher DHEAS/DHEA ratios were related to reduced processing of the negative emotional content.

    [Study of the stress response: role of anxiety, cortisol and DHEAs]. - PubMed - NCBI


    CONCLUSION: These results allow us to propose that the emergence of state anxiety is the first stress response and the primary protest . Up to a certain level, a plateau level, anxiety remains stable. Then, nature of the stress response changes and takes a biological aspect. Increased of cortisol plasma levels, the secondary protest , is observed and gives evidence of an intensified and sustained stress response. Such a gradual phenomenon is particularly reported in elevated psychological distress which is associated with loss of control. It is important to note that identical scores of state anxiety (Mann Whitney test) were observed in anxious subjects with or without rise of plasma cortisol levels. DHEAs was also implied in the stress response. The enhancement of plasma levels of DHEAs were dependent on cortisol, as shown by the close correlation between both hormones (r=0,433, p=0,0033, Spearman test). The hypothesis of an antagonism between these two hormones is based on the fact that DHEAs opposes the action of cortisol and exerts a true anticortisol effect. This antagonism might be related to a competition in their synthesis and release by the adrenal gland. In the present case, high level of anxiety (state and trait) was associated with an increase of cortisol, while low level (of anxiety) was related to an exclusive rise of DHEAs. Intermediate anxious score was observed in subjects who showed increases of both cortisol and DHEAs (p=0,0225, Kruskall Wallis test). Furthermore, a close relationship (negative correlation: Spearman test), was observed between increases in DHEAS and scores of state anxiety (r=- 0,382, p=0,06) and trait anxiety (r=- 0,0097, p=0,527). This means that the worriness and the underlying anxious ruminations and negative anticipations, which characterize trait anxiety, were less important in subjects who increased plasma DHEAs levels. In addition, emotional tension and uneasiness, which accompanies state anxiety, were also less marked. There are no studies reporting a relation between DHEA(s) and state or trait anxiety. Nevertheless, many authors have proposed a beneficial action of DHEA on the feeling of well-being. This beneficial role could be related to a double action of DHEA: a direct effect provided by its transformation into sexual hormones, an indirect one mediated by its competition with cortisol, of which the synthesis and consequently the activity decrease.
     
  9. OP
    haidut

    haidut Member

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    I think that right there is a very big part of the reason for DHEAS benefit. Vulnerability to stress in the brain is largely determined by the ability to mount a dopamine response, which keeps the brain intact. That's why young people sometimes even crave stress and to them it is not stress at all but more like "stimulation" or "excitement". Ability to co-release DHEA with cortisol is a big part of their ability to mount dopaminergic response and to oppose cortisol. In older people, there is not much DHEA/S and stress is just stress, with very bad consequences.
     
  10. Wagner83

    Wagner83 Member

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    Not only older people unfortunately. Why would someone (young or not) not be able to mount that acute dhea response?

    I do think it's interesting to see the big differences between DHEAS and dhea, it doesn't look like dheas is a mere storage pool of dhea but it has its own effects and the dheas/dhea ratio actually matter as well. I wonder what does this mean about the simplicity of supplementing dhea, as well as the numerous negative effects people have seen from it. Wasn't magnesium said to increase dheas? Perhaps an other reason to have some magnesium supplements ahead of stressful times if diet doesn't provide enough.
     
  11. OP
    haidut

    haidut Member

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    Thyroid is a major factor in that young person response, because the ability to synthesize pregnenolone/DHEA depends on it. Also, the activity of the enzyme 17,21-lyase depends on cytochrome B5, which depends on metabolism more than anything else. Interestingly, aside from thyroid, DHEA itself is a potent inducer of cytochrome B5 in HED of just 10mg-12mg daily, so it stimulates its own synthesis and allows for even better counter-cortisol response.
    When supplementing with DHEA in doses under 15mg daily the vast majority of it gets metabolized into downstream hormones and very little floats around as either DHEA or DHEAS. If a high dose of DHEA is taken orally then the excess that cannot be immediately metabolized gets converted into DHEAS. So, for most people exogenous DHEA will not stay as DHEA unless it is taken for several months (as we discussed) at which point the tissues will be saturated with DHEA and then serum levels will start to rise and thus will trigger increase in DHEAS as well.
     
  12. benaoao

    benaoao Member

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    I’m not sure if you’re comparing Fluoxymesterone to prednisone; prednisone may cause false positives.

    Also I kinda dislike the methodology they quote for Fluoxymesterone

    The effects of fluoxymesterone administration on testicular function. - PubMed - NCBI

    Get the full paper using sci-hub, the way Fluoxymesterone acts is very unique considering its structure.
     
  13. Wagner83

    Wagner83 Member

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    Thanks so the dheas levels and associated ratios they mentioned could, besides having potential dopaminergic effects, be simply a marker of tissues being replete with androgens/steroids? It would be interesting to know if there are correlations between 3-alpha-androstanediol glucoronide and dheas levels. I wonder if there are studies on stress handling with the former as a focus.
    From what they said the dheas / dhea ratio was important, and dheas levels were important too, so perhaps supplementing dhea acutely will not help enough, at least not through this pathway, since it gets converted into other hormones and it seems, for some/many people into estrogenic metabolite (not to mention depersonalization). In that case the DHEA and DHEAS could simply be..well..markers of metabolism rather than causative factors that should/could be supplemented.

    Just rambling on.. no knowledge. Nothing there..



    Are you asking me or haidut? In my post there's mostly a long quote from the study.
     
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