DHEA interactions

[Fuzzin]

Alright, I figured I would pose this question to the more educated and technical sample of people. My question is this: I plan on starting a regimen of DHEA @ 50mgs/day for testosterone increase along with tamoxifen. My worry is that I am currently on an SNRI, venlafaxine. I know DHEA is manufactured naturally in the adrenal gland however I worry that it may also increase norepinephrine output and cause an excess of NE because of the NE reuptake inhibitor, venlafaxine that I am on. I am super sensitive to stimulatory drugs/ hormones and cause me undesirable effect to say the least. I know DHEA is separate from and a different chemical than NE but cause they are manufactured by the same gland I am worried about DHEA increasing norepinephrine output and that casing probs being on a reuptake inhibitor of that chemical. So without repeating myself too much, does anyone know if I need to worry at all about this while starting DHEA. (for all you doubters of DHEA's effectiveness to increase testosterone, I've read two very recent studies that demonstrated significant increases in resistance trained men i.e. body builders.

Question #2: I also am aware that DHEA is a GABA-a antagonist ( how strong I don't know), as I currently take clonazepam, is it going to screw that up too!
Any input appreciated. No lectures about drug combos and alternative ideas, just info on these questions would be appreciated.

 

[interleukin]

I don't see any direct mechanism by which DHEA can increase norepinephrine output. It is however a neurosteroid with GABA-antagonistic + NMDA agonist* properties. I very seriously doubt it is anywhere near as potent to counter the effects of clonazepam or even have a noticeable effects if not on any drugs.
I'm more concerned about the tamoxifen though and don't want to get into why DHEA is a waste of time and money. Are you coming off a steroid cycle? If not you do realize that tamoxifen is a very powerful SERM right? It will increase your testosterone levels very significantly and will block the estrogen receptor in the brain (and in many other places) causing many possible psychological effects. Even though it will increase your testosterone levels by maybe 500 points, you won’t gain any weight from it and may even lose muscle mass. If you are not using steroids or have gyno please don't touch tamoxifen. If you are then you know better than to waste your time on DHEA.

 

[Fuzzin]

Tamoxifen has been used as post cycle therapy for years to rebalance natural testosterone levels after an anabolic steroid cycle. It has also been shown to increase testosterone levels up to 150% from baseline (multiple sources and citations for that claim) alone. I am an MMA competitive fighter and am tested for steroids that are of the testosterone family. That's why I take nolvadex. It has also been shown to be a safe alternative Testosterone replacement therapy agent in hypogonadic men. I've been on it for about 2 weeks now with no unwanted side effects except the feeling of increased test levels (and I do have minor gyno from previous steroid use). I do want you to get into the reasons not to waste my time w/ DHEA though from a chemistry standpoint. It is on the Olympics and other professional sports leagues list of banned substances and I assume that's for a reason, it increases performance. I believe it is a prohormone first converting to androstenedione (which was made famous when Mark McGuire broke the home run record was found to have been using andro and it has since been banned). From there it acts as a precursor to testosterone (and can aromatize to some estrogen but I'm covered there with the nolvadex). So if you or anyone else has input regarding this discussion please do reply. To be clear, my whole goal is to raise my testosterone levels as high as possible without actually shooting test.

 

[negrogesic]

There is no 'major' drug-drug interaction here. Nonetheless, DHEA can impart a broad range of psychiatric complaints, and exacerbate preexisting disorders (particularly if said disorders have not been 'well-controlled' via medication). 50mg of DHEA seems like a low-dose in respect to what your end-goals are, but I am certainly not advising that you take more.

This is merely an anecdotal account, but in my experience, I myself found DHEA to be noticeably more anxiogenic than a roughly 'equivalent' amount of 4-androstenedione (which needless to say, a significant dose).

Bottom Line: Pathways surrounding the neuromodulatory function of DHEA are astoundingly complex and poorly understood. If you intend to take this course, be well aware that in all likelihood, you are going to experience some degree psychiatric side-effects. How severe these will be is highly variable by person, sensitivities, etc. As you well know, fighting sports require a keen and clear mind, and it could be that DHEA may cause more deficits in this regard than any benefit imparted by potential strength gains. Or, it hold some merit in the intended outcome, while exhibiting only slight modest CNS disturbances.

And of course, exercise extreme caution when disturbing the HPTA (it an immensely temperamental system that doesn't like be fucked with).

 

[m060mm]

It seems like you're dead set on DHEA and Nolva so I won't bother. Anecdotal evidence from several guys I know: DHEA has minimal psychotropic effects. Especially with the clonazepam, I don't think you need to worry about NE increases or their potential to be anxiogenic.

_{Why is this advanced?}

 

[Epsilon Alpha]

Fixed spelling error in thread title so I don't have to hate fuck the thread
But, you might want to be weary of your body's aromatase pathway lest you end up with tits.

 

[23536]

tamoxifen can be anxiogenic and causes a lot of other nasty sides. From my experience toremifene is better.

 

[m060mm]

But, you might want to be weary of your body's aromatase pathway lest you end up with tits.

Well that's what the tamoxifen is for but +1 due to the fact that our understanding of these processes is still pretty limited. Risk to benefit.

 

[WabbaJack]

So without repeating myself too much, does anyone know if I need to worry at all about this while starting DHEA.

At 50mg you will not need to worry about overstimulation, even if you are sensitive. This is a very different mechanism.

Question #2: I also am aware that DHEA is a GABA-a antagonist ( how strong I don't know), as I currently take clonazepam, is it going to screw that up too!

Clonazepam is plenty powerful enough to prevent the GABA-a antagonist properties of DHEA, which are quite mild.

ADDENDUM:

You should consider increasing the dosage of your DHEA to at least 100mg, if not higher, 200mg max. These are the levels that you will see benefits to testosterone levels. At the same time it is good you are taking Tamoxifen, this should do more than enough to prevent most side effects, but just to cover all your bases here, I would look into white mushroom extract in order to regulate your aromatase activity (The extract is a different mechanism of action so if something else in your system is haywire, it will take up the slack). In the same vein, definitely supplement 50mg of Zinc a day. On top of your normal diet, this should be enough to see some aromatase regulation as well.

Question: Are you taking SSRIs? Taking them will increase aromatase activity and be very counter-productive in your goals. The supplements I mentioned above would be very helpful in counteracting the effects of any SSRIs you are taking, but if you want to take an extra step, use resveratrol and green tea extract, as resveratrol has been useful in treating SSRI induced sex hormone imbalances. The green tea extract will act as a gateway mechanism to get more of the resveratrol into your bloodstream.

 

[sekio]

White button mushroom extracts don't do very much -

White button mushrooms were freeze-dried and pressed into tablets containing 500 mg of powdered extract. Each tablet contained approximately 5g of whole white button mushroom. Study participants were treated with 5, 8, 10, or 13 g of mushroom extract per day for 12 weeks. Aromatase inhibition was evaluated by measuring circulating sex steroid hormone and with an assay of aromatase activity developed in the authors' laboratory. A positive response to the mushroom extract treatment was defined as a decline in free estradiol (E2) of 50% or higher. White button mushroom extract up to 13g per day was found to be well tolerated, with no adverse side effects.

None of the participants met the pre-defined response threshhold of a 50% reduction in free estradiol. In fact, free estradiol was found to trend upward over the 12-week treatment period for women in the 5g and 8g dose groups and remain stable among the 10g and 13g groups.

Nothing natural will ever come close to the efficacy of tamoxifen as an aromatase inhibitor. And in the end there aren't different "mechanisms of action", either the drug blocks the protien aromatase from functioning or it does not.

And 50mg of zinc is a rather high dose, is it not?

 

[Epsilon Alpha]

Question: Are you taking SSRIs? Taking them will increase aromatase activity and be very counter-productive in your goals. The supplements I mentioned above would be very helpful in counteracting the effects of any SSRIs you are taking, but if you want to take an extra step, use resveratrol and green tea extract, as resveratrol has been useful in treating SSRI induced sex hormone imbalances. The green tea extract will act as a gateway mechanism to get more of the resveratrol into your bloodstream.

Source on the SSRI bit?

 

[WabbaJack]

White button mushroom extracts don't do very much -



Nothing natural will ever come close to the efficacy of tamoxifen as an aromatase inhibitor. And in the end there aren't different "mechanisms of action", either the drug blocks the protien aromatase from functioning or it does not.

And 50mg of zinc is a rather high dose, is it not?

As far as the white button mushrooms, it appears they do something, but I am having trouble finding effective dosage, so you may be correct if the dose required is high enough. http://www.ncbi.nlm.nih.gov/pubmed/17178902


Zinc 50mg is high, but the benefits as an aromatase inhibitor do not start until 100mg to 150mg.
http://www.ncbi.nlm.nih.gov/pubmed/8613886
http://www.ncbi.nlm.nih.gov/pubmed/3207614

either the drug blocks the protien aromatase from functioning or it does not.

I apologize, I am nitpicking here, but should we refer to aromatase as an enzyme instead of a protein? (even though it is a protein, its role as an enzyme is why it's important)

One lesser known mechanism of inhibiting aromatase is by binding to and activating Aryl Hydrocarbon in the liver, which actually increases aromatase, but certain naturally occuring substances in food such as Diindolylmethane (notably Broccoli) bind to Aryl Hydrocarbons and are less effective at producing aromatase and as a result, less aromatase is produced. Also, there is competitive inhibition and non-competitive inhibition of aromatase correct? Further, some substances act indirectly on the inhibition of aromatase, such as by increase levels of the hormone 4-hydroxytestosterone which itself is an aromatase inhibitor produced by the body when certain drugs are introduced. Also, White Button Mushrooms act on aromatase through linoleic acid. These substances are not acting as an aromatase inhibitor, but are inducing other aromatase inhibitors. I don't think we can simply say a drug (or other substance) either blocks aromatase from functioning or not, especially since some will lower net aromatase levels. This does not necessarily prevent the aromatase that does get produced from functioning, but when there is less of it, there is less conversion of testosterone to estrogens. The important thing to note here is that by utilizing the different methods of action, we can have a stronger effect on aromatase inhibition through synergistic methods of action.

 

[WabbaJack]

Source on the SSRI bit?

Ah you caught a mistake, sorry about that. I must have equated libido decrease with aromatase activity. It turns out SSRIs act on prolactin, not aromatase, which results in the sexual dysfunction, and is treated with dopamine agonists normally. However, while I was looking for the source I read recommending resveratrol to treat SSRI sexual side effects, I am also finding out that a recent study is showing an increase in cAMP levels through inactivation of phosphdiesterases by resveratrol, so this seems counter-productive (since cAMP can increase prolactin). Perhaps its role as an aromatase inhibitor counteracts this effect making it useful in treating sexual side effects from SSRIs.

 

[Epsilon Alpha]

Ah you caught a mistake, sorry about that. I must have equated libido decrease with aromatase activity. It turns out SSRIs act on prolactin, not aromatase, which results in the sexual dysfunction, and is treated with dopamine agonists normally. However, while I was looking for the source I read recommending resveratrol to treat SSRI sexual side effects, I am also finding out that a recent study is showing an increase in cAMP levels through inactivation of phosphdiesterases by resveratrol, so this seems counter-productive (since cAMP can increase prolactin). Perhaps its role as an aromatase inhibitor counteracts this effect making it useful in treating sexual side effects from SSRIs.

All good, but just a friendly heads up its good to post sources when making claims in ADD unless its a widely accepted fact (ex: amphetamine releases more NE than DA).
As an aside: cAMP, Ca2+, cGMP and most other common second messengers are more what/where/when than classical transmitters so be cautious making claims on "cAMP does xyz" vs "cAMP due to abc signalling does xyz in 123 cells".

Not trying to sound like I have a raging superiority complex, just trying to help out the new guys

 

[WabbaJack]

All good, but just a friendly heads up its good to post sources when making claims in ADD unless its a widely accepted fact (ex: amphetamine releases more NE than DA).
As an aside: cAMP, Ca2+, cGMP and most other common second messengers are more what/where/when than classical transmitters so be cautious making claims on "cAMP does xyz" vs "cAMP due to abc signalling does xyz in 123 cells".

Not trying to sound like I have a raging superiority complex, just trying to help out the new guys

Thanks for the heads up, I was looking for the specifics of the cAMP mechanism in this case but it appeared to be a general increase, which seems odd to me because although I am new to studying cAMP, all the examples I have seen so far show it localized to certain areas rather than a global increase. You seem to confirm it to be a localized mechanism... so I am further doubting this global increase in cAMP levels...

Thanks again, I am still learning.

BTW, I finally found my original source on the SSRIs increasing aromatase activity, and... it turns out I got it completely backwards. SSRIs actually decrease aromatase by increasing prolactin, yet still they manage to decrease libido. And here is a source for that: http://jop.sagepub.com/content/11/4/345.short

After 3 weeks paroxetine treatment plasma prolactin levels were significantly higher than those seen either pre-treatment or after 1 week of treatment."

Sorry for the scatter-brainedness. I need to stop mixing up "increasing" and "decreasing" in my head. The chain of an increase in one leading to a decrease in another is probably what got me though.

 

[Fuzzin]

Wow

 

[Fuzzin]

I do think the combination of this post and other research, I've got my answered to a satisfactory extent, thanks