HPTA suppression from AAS vs other suppressive biochemical pathways

[Rubato]

It seems to me that the more I read about exogenous testosterone administration, the more it seems to differ from other chemical manipulations in the body, even those within the HPTA axis. After administration of any exogenous AAS (like testosterone), the HPTA axis begins to suffer almost immediately. LH secretions drop, GnRH secretions drop, endogenous testosterone production plummets, and the leydig cells in the testes become almost useless. When one stops exogenous administration, this situation does not correct itself very well, especially without pharmacological intervention. A battery of medications from one or more selective estrogen receptor modulator to HCG may be used to help restore pituitary and testicular function in post cycle therapy. While this helps, it is not guaranteed that HPTA axis function will ever return to previous baseline levels and may be forever impaired.

Why doesn't the body correct itself, even if it takes a long time? It doesn't seem to work this way across other seemingly similar biochemical pathways.

Let's talk about dopamine, for example. I have taken dopamanergic medications for an REM sleep disorder off and on for 2 years or so now under the direction of a neurologist. It will probably be impossible to legitimately compare this to testosterone because I never assessed and am not sure if it's possible to assess my endogenous levels of dopamine prior to starting the medications.

All I know is that within a few weeks of cessation from either methylphenidate or amphetamine (provided it's been properly tapered... this is not true of cold turkey cessation, which is very painful) I feel exactly like I felt previously.

As far as the data I've seen, within a few months of total cessation from dopamanergic drugs, there is no greater downregulation of DAT action, dopamine receptor number, or dopamine production from baseline. When you start talking about substituted amphetamines like methamphetamine and ecstasy, this does not hold 100% because there is a higher level of neurotoxicity associated amphetamine substitution and I'm not aware of the precise mechanism of action.

I've also noticed this same thing to be true in my case of gabanergic medications. This lies outside of the HPTA axis but demonstrates tolerance, down-regulation of gaba receptors, receptor ligands, and dependence with prolonged use. Again, I've never had my gaba levels assessed, but from a qualitative point of view, I do not notice any changes. The literature I've read does not make note of permanent neurological changes within benzodiazepam or barbiturate users within 6 months of cessation, so far as I'm aware.

And then there's testosterone. 4 months of exogenous administration can totally suppress HPTA axis and render the leydig cells significant less useful from anywhere to a little while to a lifetime. Granted, gaba is a neurotransmitter, a totally different chemical class from the hormone, but dopamine is a neuro-hormone. A peptide hormone rather than a steroid, but still a hormone.

I've thought about other biochemicals that fit the same sort of profile as testosterone, opioid receptor agonists and even estrogen analogues used for female birth control. They don't seem to work like testosterone. And if anything was going to work like testosterone, it would seem that estrogen analogues would. The only complaints you see with women who take them as birth control seem to be very non-serious things like bloating, weight gain, and more seriously (and rarely), estrogen sensitive breast cancer.

After thinking about this, I've come up with 4 reasons why this may be:

1 - my examples don't hold because the biochemical's endogenous levels were not raised directly by exogenous administration, but indirectly through receptor modulation. At the end of the day both mechanisms result in the same thing - higher endogenous concentrations of the chemical in question - but the mechanism of action is different. I don't know if this is significant or not.

2 - The negative feedback component of the testicular portion of the HPTA axis is more sensitive than the other negative feedback components of the axis and of other biochemical mechanisms of concentration control.

3 - My examples are flawed because no biochemical levels were assessed before and after. Subjective feelings do not indicate real bio levels. I could be suppressed and not know it.

4 - Excessive levels of testosterone are either directly or indirectly toxic to a component of the HPTA axis, either as a result of the chemical itself, or as a result of an unknown metabolite of a chemical process in which it is involved. Another possibility is that a component of the HTPA axis is dependent on a product of the negative feedback pathway and when it is absent, so too is the necessary chemical.

Thoughts?

 

[marmel75]

All I know is that you are golden if you can get the body to produce more Testosterone via various pathways(SHBG binding, SHBG reduction, LH increase, enzyme enhancement, etc). However once you bring in an exogenous form the body believes it doesn't need to produce it anymore because the levels are so high.

DHEA does not have a feedback loop like that, so transdermal application of that can result in higher intracellular androgen levels...

 

[Rubato]

All I know is that you are golden if you can get the body to produce more Testosterone via various pathways(SHBG binding, SHBG reduction, LH increase, enzyme enhancement, etc). However once you bring in an exogenous form the body believes it doesn't need to produce it anymore because the levels are so high.

DHEA does not have a feedback loop like that, so transdermal application of that can result in higher intracellular androgen levels...

But isn't what I bolded in your response the same reason why people using dopamanergics, gabanergics, or opiates experience a "crash" if they suddenly stop? The administration of a compound that artificially increases levels of whatever biochemical in question will fool the body's negative feedback process in to thinking the chemical is present in sufficient supply and that it doesn't need to produce any more.

I don't know that the pathway really matters. If it did, an LH analogue like HCG or HMG would not be suppressive, and they appear to be suppressive to the HPTA axis.

I have never heard that DHEA does not have a feedback loop associated with it and always assumed it was a rather worthless supplement because, if my understanding is correct, the negative feedback suppression of the HPTA axis would eventually convert any excess androgen to estrogen. And if it did that, it could cause negative feedback on LH, which could in turn reduce testosterone production because the elevated estrogen(s) level is fooling your pituitary in to thinking there is too much testosterone (since men make their estorgens from testosterone). At least, that's what I learned in my endocrinology class.

Even the SARMs that bodybuilders are experimenting seem to be mildly suppressive when used at useful anabolic dosages, and these chemicals are absolutely foreign to the human body. They aren't elevating testosterone levels per se, but their mechanism of action is similar to that of what testosterone's would be in that it's an anabolic/androgenic substance, albeit in differing ratios. But still, the whole idea behind a SARM was that it was supposed to give the benefits of AAS without the suppressive sides - low doses do not appear to be suppressive but they also do not provide much benefit. The anabolically useful dosages appear to slightly elevate ALT levels and suppress endogenous testosterone levels in post cycle blood work.

I am not very familiar with the biochemistry of SHBG or how enzymatic enhancement would upregulate testosterone levels. If you have some insight I don't have, I'd love to hear about it. You give top notch diet advice

 

[marmel75]

That is why you should always take DHEA transdermally since the areas around the back and shoulders preferentially convert it into Testosterone. If taken orally its a crapshoot unless you are taking it with something that strongly shifts balance towards Testosterone...

 

[marmel75]

Rubato, regarding SHBG, it is a protein called sex hormone binding globule that floats around and binds to Testosterone rendering it inactive. There are a couple methods here, the first being things that have a higher affinity to SHBG than T does. Divanil, or stinging nettle root extract and the "good" form of estrogen both have a higher affinity to SHBG than Test does. DIM or diindolylmethane, the metabolite of Indole-3-Carbinol, found heavily in brassica vegetables(broccoli, cauliflower, kale, etc) upregulates the conversion of estrogen into its "good" form. Borax reduces the production of SHBG. Both of these increase the levels of free testosterone in the body, since there is less SHBG available to render it inactive.

Enzymatically, both olive oil and coconut oil increase the amount of cholesterol uptake by
the leydig cells in the testes and also helps to de-esterize it. It also increases the rate at
which the 2 main enzymes responsible for converting cholesterol to testosterone convert it.
Basically the more cholesterol the leydig cells absorb and the less esterfied it is, the more testosterone gets produced.

 

[Rubato]

That's super interesting marmel... thanks for the info.

It's hard for me to imagine that supplementing with olive/coconut oil and broccoli would significantly increase free levels of testosterone. I already use these as my exclusive oils, and eat broccoli every day... so it's hard for me to say.

I've never tried any of those supplements you mentioned. Are there any studies confirming their biochemical efficacy?

And I've never heard about the transdermal DHEA either.... what sort of increase could you expect by employing the methods you've mentioned here? Anything significant enough to warrant purchasing a new supplement? And would it be suppressive?

 

[Down Low]

Just take Clomid at 25-50mg for 25 days on, 5 days off, for a few months. It will help restore your natural testosterone production.

 

[Rubato]

Just take Clomid at 25-50mg for 25 days on, 5 days off, for a few months. It will help restore your natural testosterone production.

My natural test levels are great. I'm not suppressed. I'm just curious why this biopathway seems to work differently than others of a similar nature.

 

[marmel75]

That's super interesting marmel... thanks for the info.

It's hard for me to imagine that supplementing with olive/coconut oil and broccoli would significantly increase free levels of testosterone. I already use these as my exclusive oils, and eat broccoli every day... so it's hard for me to say.

I've never tried any of those supplements you mentioned. Are there any studies confirming their biochemical efficacy?

And I've never heard about the transdermal DHEA either.... what sort of increase could you expect by employing the methods you've mentioned here? Anything significant enough to warrant purchasing a new supplement? And would it be suppressive?

Coconut and olive oil would increase levels of total T..basically the more fat you eat(cholesterol) the more T gets produced, and these are the best of the best in regards to that. Broccoli and brassica vegetables also have another, more interesting effect, in that they actually help to stimulate the creation of new muscle cells in the muscle.

Borax dosage was 10mg in the morning in the study. Increased free test an average of 28% I believe.

Trans DHEA will not show any increases in androgen levels in testing, because the cells absorb it directly without it getting processed by the liver and turning into DHEA-S.
Certain areas of the body preferentially convert the DHEA into T or E(after it gets converted into Andro). Shoulders and upper back preferentially into T, stomach are into E.
There is no feedback loop for DHEA, so you cannot shut off your body's production of it.

You should go listen to segments of Rob Regish on superhumanradio.com, he talks about stuff like this a lot and is where I get a lot of my info...I text/talk with him quite a bit...he knows his stuff backwards/forwards/upside down and any other way you can think of...

 

[marmel75]

Rubino, another method of increasing T is through free radical scaveging by antioxidants in the testes. Garlic, onions and ginger all contain very strong antiocidants that scavenge free radicals in the testes. The fewer free radicals, the less testosterone gets damaged and the more ends up being available.