Least toxic anabolic enhancement methods

Previously from the other dutch forum I linked (no link anymore) I only read the first and last reply with a translator. I looked again at the middle of it and there's a counterargument made with another study on pubertal boys. However, the oldest boy in this study responded closer to the way men responded in other studies. Consider how differently females responded in previous studies, it isnt surprising that children don't respond well either. So, this is still the only negative study suggesting that only in pre - mid pubertal boys opioid antagonists don't raise LH. https://dacemirror.sci-hub.st/journal-article/22403cee2b654cd47185d1637b017f3e/kletter1991.pdf


"To determine whether naloxone can reverse the suppressive effects of T on mean LH concentrations and LH pulse frequency, we studied eight boys (Table 1, boys9-16) according to the protocol depicted in Fig. 1. Results from boys 9, 12, and 15 are shown in Fig. 3. Patient 9 (Fig. 3A), an early pubertal boy, showed neither an increase in mean LH concentrations nor pulse frequency in response to naloxone during either saline or T infusions. Patient 12 (Fig. 3B), a midpubertal boy, demonstrated a rapid response to naloxone during the saline study, but no response during T infusion. Patient 15(Fig. 3C), a late pubertal boy, also responded to naloxone during the saline infusion with increased LH pulse frequency and mean LH concentrations; during infusion of T, he had a slow frequency, high amplitude pattern of LH secretion, which did not change during naloxone treatment."

Where T infusion started at 10am on the second day.
"During T infusion, mean T was 19.8 ± 2.0 nmol/L between 1200-1800 h."
4 hourly doses 0.1mg/kg naltrexone. The oldest patient (C) appeared to respond well to naloxone and mean LH was close to baseline even after T infusion. Although only adults showed additionally increased frequency of LH pulse when administered with estradiol-17β.
Screenshot_20231227-095358_Drive.jpg


"As reported previously, pituitary responsiveness to exogenous GnRH administration did not decrease after T infusion, indicating that testosterone's negative feedback effects occur primarily at the brain/hypothalamic level (2, 4, 5).

It is well accepted that in normal men, opioid receptor blockade increases LH secretion (6-10). In contrast, prepubertal and early pubertal boys do not manifest this phenomenon and appear to experience a paradoxical inhibition of LH secretion by naltrexone (12-17). Thus,
at least in males, the ability to respond to opioid receptor blockade appears to develop at about midpuberty (1, 2). Our findings support this, as only the boys who had more advanced pubertal maturation responded to naloxone with an increase in LH secretion.
"

I'll keep searching, maybe other studies which cited this study will show something interesting. So far all studies on adult men are positive unless low doses (below commonly percribed) are used.
 
Found one relevant study, so far the first to state that opioid blocking doesn't work in men with exogenous testosterone. https://zero.sci-hub.st/4651/30c8451800f76b5c4bc5b233cb7cab12/kletter1992.pdf

In the discussion section they say it could be due to them using low doses. And also the infusion of T was started prior to naloxone treatment, while I talked about doing them either both simultaneously or naloxone even earlier, it's supposed to have a longer half life than both estradiol and T, but if needed two naloxone doses can be taken.
 
Found one relevant study...
Wtf did I write? That's why I shouldn't jump to conclusions, literally, I should always read the whole data not hurry-post. Here is the finding:
Administration of naloxone increased mean plasma LH concentrations significantly during saline infusion (7.6 to 10.0 IU/L), but not during T infusion (6.9 VS. 7.3 IU/L).

So? On average the men had their testosterone increased 2.5 fold by testosterone infusion. And still LH "insignificantly increased by naloxone" - when the increase still exists, at least there is no suppression if LH went from 6.9 to 7.3.

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First Update 4 days after reply to avoid unnecessary notifications:

To start, this may be intersting: https://karger.com/nen/article-abst...apid-Naloxone-Induced-Alterations-of-Androgen




"It is well established that, during aerobic EX, the heart also undergoes acute pressure overload. Repeated pressure overload via EX is responsible for eccentric cardiac hypertrophy, which increases SV and CO over time. Therefore, although the rats studied by Dehe et al. [31] were observed chronically, the results of the study may provide another potential mechanism for the cardiodepressant effects demonstrated in our study. It is possible that NTX can cause an acute downregulation of cardiac opioid receptors during EX and, therefore, alter LV function. During pathological pressure overload, this effect would be of benefit and potentially decrease the risk/rate of LV hypertrophy and improve cardiac function, chronically. However, when combined with chronic EX, it is possible that NTX can interfere with positive EX adaptation"

Notice they did cardio exercise, and long acting naltrexone. I already planned for cardio in the morning without PED or antiopioids end weight training at noon fueled by test & naloxone.








These and many others tell me that the heart, main target of steroid harm, could suffer even more with opioid antagonism. Although intranasal administration partitions it to the brain the heart won't be exposed to it any less. But I could be misunderstanding it if the papers themselves are even conclusive with this situation.

Certainly I'm not educated in anything cardiology, help me out if you understand this more. Isn't "cardiac hypertrophy" sometimes a good thing? With AAS certain areas grow and other parts of the heart shrink, right?

Another interesting clue https://karger.com/neo/article-abstract/82/3/207/369169/Exposure-to-the-Opioid-Antagonist-Naltrexone
As well as

And still testosterone definitely increases opioid activity, so it might just be finding the balance. https://www.science.org/doi/full/10.1126/scisignal.aba1169



While naloxone had a protective effect in arrhythmia caused by adrenaline infusion, really interesting:
"The opiate antagonist naloxone reduced the incidence and severity of cardiac arrhythmia induced in rats by intracarotid administration of adrenaline. Naloxone also reversed the adrenaline-induced arrhythmia in isolated heart preparations, suggesting a local antiarrhythmic action of the opiate antagonist. Similar effects were obtained with the (+) stereoisomer of naloxone which is inactive as an opiate antagonist. Thus, the direct action of naloxone at the rat heart is probably not mediated by opiate receptors."

Multiple articles point to naloxone protecting kidneys https://journals.physiology.org/doi/abs/10.1152/ajpendo.1988.255.6.e839

"The present data demonstrate that naloxone significantly attenuates the development of hypertension in two-kidney one-clip rats. The attenuation of blood pressure was not associated with the changes in PRA, renal renin activity, or plasma aldosterone concentrations."


And in some scenarios the heart
Screenshot_20231231-102812_Drive.jpg
I'm the furthest thing from a cardiologist.



https://thejns.org/view/journals/j-neurosurg/64/5/article-p780.xml

Another time I'm seeing "naloxone benefits heart" in a scenario: https://academic.oup.com/cardiovascres/article-abstract/29/1/80/317382

Just imagine if you could take steroids, and with a single drug reverse pituitary suppression as well as heart complications... doesn't appear to be the case though if opioids negatively regulate heart growth and generally AAS users have a larger heart.

I don't think everything about cholestrol is straightforward either, but if stress induced hypercholesterolemia is bad then opioid blockade reverses it https://www.sciencedirect.com/science/article/abs/pii/0006295288904157

Not exactly relevant, or is it? Something to keep in mind, hypertensive people respond with greater increased cortisol upon naloxone dosing than normotensives.

More intriguing big words:


"Agonists selective for the κ- and δ-opioid receptors, but not μ-opioid receptors, induced a concentration-dependent decrease in cardiac function. The decrease in left ventricular systolic pressure on administration of the κ-opioid receptor-selective agonist, U50488H, was attenuated in hearts from hamsters subjected to chronic, untreated hypertension (P < 0.05) compared with control. These results show that peripheral and myocardial opioid expression and signaling are altered in hypertension."

Finally,

"Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload."

While many of these articles contain big words, obviously there are those cases where opioid blockade benefits the heart.

End of first edit.
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Edit 2 after 15 minutes:

Heart hypertrophy probably remains the main issue. I do remember that even high doses of creatine cause it.

Based on the chart https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412093/

Everything else can be fought against with supplements. Cholestrol, hematocrit, nitric oxide, antioxidants. I don't know of what you can do against heart hypertrophy if you also want muscle hypertrophy.



Another side effect: https://link.springer.com/article/10.1007/s10517-012-1609-8

Yet in the very first thread (on another board) I mentioned cyproheptadine as a way to lower cortisol and prolactin while mildly boosting LH, it is also effective for aldosterone.

Edit 3... https://journals.physiology.org/doi/abs/10.1152/ajpregu.1995.268.3.r723 opioid blockade caused sodium loss. Is that the mechanism of raised aldosterone? In that case simply even higher sodium supplementation than normal, will be useful during opioid antagonism.

Final edit 4 hours later: if the main goal of not being suppressed is achieved, I'm thinking of throwing in losartan, in case if blood pressure goes high from naloxone and can't be managed with normal supplements.

week later: blocking receptors leads to increased blood concentrations, it must be dose dependent and I'll have to find out how to benefit from opioid rebound.


I feel dumb for not discussing it earlier, it seems one wouldn't even need opioid inhibition in order to do the same thing https://academic.oup.com/jcem/article/81/5/1772/2650040
perhaps a pge2 agonist is what we need, a lot of VIVO studies talk about GnRH sensitivity to pge. Why the hell is nobody talking about it? There's this whole department of childbirth and pregnancy...

Anyway nalоxone is a really useful for behaviour modification and lowers orgasmic prolactin release.

Just updating as I learn.. https://www.frontiersin.org/articles/10.3389/fvets.2021.753796/full these are female animals.. different story. PGE2 doesn't seem to work as a hormone booster.

https://sci-hub.st/https://doi.org/10.1016/0306-4530(80)90026-8 seems to double growth hormone in healthy men while not changing prolactin. I'm getting eager to see the gains when combined with testosterone. Screenshot_20240109-203915_Drive.jpg
 
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I’m interested in the results. Please keep us posted and share the data you obtain. I’m gonna propose that we make an experimenter’s section. It’ll be fun to read the thought process, procedures, and the results of novel experiments. It might lack full data due to restrictions (lab, equipment, participants, etc.) but it will give us some idea of what might work.

I have a couple of things to contribute with. Just don’t expect me to post results while I turn into Mr. Hyde. 🤣🤪
 
I’m interested in the results. Please keep us posted and share the data you obtain. I’m gonna propose that we make an experimenter’s section. It’ll be fun to read the thought process, procedures, and the results of novel experiments. It might lack full data due to restrictions (lab, equipment, participants, etc.) but it will give us some idea of what might work.

I have a couple of things to contribute with. Just don’t expect me to post results while I turn into Mr. Hyde. 🤣🤪
I wonder if a moderstor can make this thread accessible only to members who are logged in. Wouldn't want this to be found by those I ordered nal0x0ne from or those at b0rder control to figure out the reason I'm imp0rting. Although it's likely already chached by google and whoever else.

I also just posted at meso forum a slightly different thread. Maybe it sounds like mental masturbation to those already pinning. Especially to those who recovered fast with no issues after their cycles. I think it's worth exploring as a superior more cost effective and likely more convenient way. No need for HCG to keep the balls full...

Here was my new thread:
There are multiple studies on different prostaglandins similar to this https://www.sciencedirect.com/science/article/abs/pii/0090698076901039

Although the androgenic side effects apply even if the androgens are endogenous, problems like infertility and testicle shrinkage can be avoided. People already went with HCG as a step above exogenous testosterone. It is obvious that HCG replaces LH, therefore gonadotropins fall as much as they would with exogenous testosterone. Quitting HCG you'll still be suppressed afterwards.

Then why not go another step higher and raise endogenous LH? Is it lack of science, or proven side effects, or proven insufficient benefit, or people just don't think about it, or is it proven effective and hidden for some sort of profit selling the strictly regulated testosterone?

Obviously prostaglandins are biologically active in a variety of ways, another prostaglandin was tested for potency in men https://www.sciencedirect.com/science/article/abs/pii/S0022534717359062
And still it must be not too difficult to isolate the GNRH stimulating effect. Any research I may find useful?
 
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