T Nation

What is TRT and What is NOT TRT

I inject 30mg every day via subq and my total T is 1019 ng/dl (last time I tested it).

Yeah, I get what you’re saying. I suspect cellular /metabolic issues is why some guys don’t feel wll unless their test levels are really high, not all but some.

So you’re kinda left with just trying stuff. All I can recommend there is to make only one change at a time and keep a journal of what’s going on in your life, diet, exercise, stress, sleep, etc and how you feel. It’ll really help you build on small improvemens.

Also keep in mind everyone feels better or worse at times, just because something is off doesn’t necessarily mean that you’re on the wrong track now the journal will help you track trends above the daily experience.

Good luck.

Thanks for the encouraging words. I’m 70 and so effing tired of chasing this or that as I try to restore some degree of physiologic function(sex, sleep, energy) but giving up isn’t an option. Bipolar illness is a neuro-endocrine disorder, thus circadian rhythm is out of wack, as are hormones. If I had this knowledge and intensity when I was young, I would have gone to medical school. Now, I’m trying to save my life. There’s an irony there that I’ve become an amateur endocrinologist/pharmacologist as I try to compensate for the damage done by bipolar. All of this to get a reliable erection and make love to my wife.

I see the AI Wars are still raging over multiple threads. Here’s a link to previous post and multiple posts that I did in the attached thread on a number of topics.

To summarize:

  1. peer-reviewed scientific literature
  2. anecdotal experience of many men
  3. clinical experience of physicians

indicates that the selective use of an AI/SERM will benefit some men at some point in their lives (during the vast history of the universe). I can say this with a reasonable degree of certainty based on the available evidence.

This is not the same position that most guys need an AI while on TRT or all guys on TRT need an AI or whatever other variant you want to state. Heck, if you carefully read the literature, you can read about clear and compelling cases of men who benefited from AI use while not on TRT.

Excellent summaries by @roadie and @Chris_Colucci and @swoops39 and many others.

Major props @swoops39 for actually reading the studies sir!

Also, welcome @kazuya_mishima1!

One thing I regret is going back and forth in this thread over and over in an unwinnable war against faulty logic. Hence, I figured I’d add some info on the AI topic since this thread sort of got sidetracked.

Hat tip to @unreal24278 for his comments on the potential sampling/survivorship bias issue that I kept trying to get Danny to understand over and over and over again.

Finally, it’s sadly comical that the same group of internet experts/TOT proponents who push 150-200 mg/week of TC as a mean starting dose have a tendency to also adamantly trash judicious use of AIs. For a not insignificant segment of the T-using population this seems extremely cruel to me (for a number of reasons). To be fair it could be cruelty or ignorance. As an alternative, how about starting closer to 80-100 mg/week and see how that goes (you know, the whole minimum effective dose thing)?

Full disclosure, no AI here for me at 70 mg/week of TC.

Have a great day.

P.S. To those that pinged me but didn’t get an immediate response, my apologies. I’ve been put on restriction given my tendency to way overpost/overdetail on here :slight_smile:

I wish you all a very Happy 2021.


Interesting picture emerging on the long-term impact of supra-physiologic testosterone levels. Note the dosages/frequency below and correct with HED conversion factor for rat or mouse.


Question becomes how lucky you feel running high T levels with your DNA.


Materials and Methods


All experimental protocols were performed in accordance with the National Council for Animal Experimentation Control and were approved by the Ethics Committee on Animal Use of the University of São Paulo, Ribeirao Preto, Brazil (Protocol n° 032/2018). Male C57BL/6J wild-type (WT) and NLRP3 knockout (NLRP3−/−) mice (12-week-old) were obtained from the Isogenic Breeding Unit at Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil. Mice were maintained in a temperature (22 ± 1°C) and humidity (50–60%) controlled room on a 12-h light/dark cycle with ad libitum access to food and water.

WT and NLRP3−/− mice were treated with testosterone propionate (TP) 10 mg/kg or vehicle (peanut oil), subcutaneous injections, for 30 days. Animals were divided into four experimental groups: (1) WT_Vehicle; (2) WT_TP; (3) NLRP3−/−_Vehicle; (4) NLRP3−/−_TP.

The current study has strengths and limitations. The experiments rigorously followed stringent quality criteria in experimental research such as randomization, manipulation and evaluations performed in a blinded fashion, controlled physiological parameters and use of control groups of health animals. A major limitation of the current study was the in vivo approach, which restricts mechanistic investigations of tissue-specific inflammatory pathways, since it does not allow identification of the specific cell types responsible for the observed systemic changes. Considering that the primary goal of this study was to directly investigate mechanisms of impaired vascular dysfunction induced by high systemic levels of testosterone, to overcome this limitation we also addressed the effects of testosterone on isolated vessels. The analysis of molecular mechanisms involved in testosterone-induced activation of NLRP3 was supported by the in vitro approaches. However, results observed on in vitro assays, although important, often fail to translate to similar results in vivo . Additionally, although DHE has been extensively used DHE to detect O−2 in cells or systems, the interference from other oxidative radicals prevents a fine tune quantification of O−2 (66, 67). Since every method has shortcomings, we used a combination of DHE, lucigenin and pharmacological inhibitors to better evaluate O−2 production. In the present study we have not used aromatase or 5-alpha reductase inhibitors to determine whether estradiol or dihydrotestosterone contribute to testosterone effects. However, in previous studies, testosterone effects were not blocked or modified by anastrozole (aromatase inhibitor). Finally, the time of treatment as well as the dose of testosterone were based on previous studies that investigated other metabolic and cardiovascular parameters in different experimental models.


Our findings provide evidence that supraphysiological levels of testosterone impairs vascular function via activation of the NLRP3 inflammasome in vascular cells. The generation of mitochondrial ROS is crucial for activation of the NLRP3 inflammasome. Pharmacologic inhibition or genetic deletion of the NLRP3 in mice protects from testosterone-induced vascular dysfunction. Our study highlights the importance of NLRP3 inflammasome in vascular dysfunction promoted by supraphysiological levels of testosterone.


Androgen therapy provides cardiovascular benefits for hypogonadism. However, myocardial hypertrophy, fibrosis, and infarction have been reported in testosterone or androgenic anabolic steroid abuse. Therefore, better understanding of the factors leading to adverse results of androgen abuse is needed. The aim of the present study was to examine the impact of high dose of androgen treatment on cardiac biology, and whether exposure duration modulates this response. Male rats were treated with 10 mg/kg testosterone, three times a week, for either 4 or 12 weeks; vehicle injections served as controls. Four weeks of testosterone treatment induced an increase in ventricular wall thickness, indicative of concentric hypertrophy, as well as increased ejection fraction; in contrast, both parameters were blunted following 12 weeks of high‐dose testosterone treatment. Cardiac myocyte contractile parameters were assessed in isolated electrically stimulated myocytes (sarcomere and intracellular calcium dynamics), and in chemically permeabilized isolated myocardium (myofilament force development and tension‐cost). High‐dose testosterone treatment for 4 weeks was associated with increased myocyte contractile parameters, while 12 weeks treatment induced significant depression of these parameters, mirroring the cardiac pump function results. In conclusion, chronic administration of high‐dose testosterone initially induces increased cardiac function. However, this initial beneficial impact is followed by significant depression of cardiac pump function, myocyte contractility, and cardiac myofilament function. Our results indicate that chronic high‐testosterone usage is of limited use and may, instead, induce significant cardiac dysfunction.

In conclusion, our present results demonstrate that short‐term administration of testosterone induces a positive impact on cardiac contractile function, even at supraphysiological concentrations. However, the duration of treatment becomes a key factor in determining the outcome. Prolonged high‐dose treatment with the hormone led to maladaptation and depressed cardiac pump function and cellular contractility mediated, in part, by depressed cellular calcium homeostasis and myofilament function. Further study is required to fully understand the cellular and molecular mechanisms underlying the cardiac pathology associated with supraphysiological exposure to testosterone. Regardless, our current findings support the notion of a severe negative cardiac impact of nontherapeutic use of androgenic steroids.

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It’s because people love to make something simple more complicated. Have low testosterone… take some testosterone. Not too much and you’re good. I guess it would make for a boring forum.


So, 160/wk still leaves you at suboptimal levels at times.

What is optimal?

@readalot you were restricted by this forum? Why would they silence you? I don’t particularly like that.

Anyway, do you think there is an optimal free t that men on trt should be on?
And if the answer is depends on symptoms, can you tell us where you think most men are at in terms of free t that are doing well?

Personally I am in the upper range of free t , just concerned if these levels as I age can be detrimental to other bodily functions and systems.

I literally have no idea what you’re talking about.

Nope, he was not.

Haha, things can quickly escalate on the forum with poor phrasing (not enough detail). What I should have said was “put on restriction by the boss at home!” Much worse than being restricted by the Forum Mod.

Sorry for confusion and thanks for checking @trtwuzup. Wasn’t trying to mislead anyone @Chris_Colucci. Thanks for checking in.


For the record I figured you were talking about your house CEO, I can relate lol. I limit my forum time to the few minutes I can sneak at work.

Just a note about the AI battle, and again anecdotal but that is what I value in forums. I can google studies all day long. I drank the Kool-aid, no AI. Had blood work, E 2 very high. Doc asked if I was taking the AI and I told her that everything I was reading said not to. She told me forget the bro science and take it. I take .125 per week on average, made the TRT optimal for me. Glad to see some cooler heads on the topic prevailing, I was absolutely turned off before the banning and almost left the forum (TRT only, love the pharma section) because it became unreadable.



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I posted this information in the thread previously but I am sure it was drowned out by the entertaining exchange late last year.

For the thoughtful TRT patient who wants to understand and make sense of their direct free Testosterone blood results and why the results don’t seem to make sense. This question comes up quite a bit and many times the answers provided propagate the incorrect information and explanation.

Well put. Here’s some of the latest published thinking on this topic (free hormone hypothesis, free T importance) attached below (last updated Oct 2020). Personally my free T stays within range since my TT stays within range. For those with very high or very low SHBG, this is more of a challenge.

Transfer of hydrophobic steroids into tissues is presumed to occur passively according to physicochemical partitioning between the hydrophobic protein binding sites on circulating binding proteins, the hydrophilic aqueous extracellular fluid and the lipophilic cellular plasma membranes. According to the free hormone hypothesis (78-80), recently restated and updated (62), the free (non-protein bound) fraction of testosterone is the most biologically active with the loosely protein-bound testosterone constituting a less accessible but mobilizable fraction, with the largest moiety tightly bound to SHBG constituting only an inactive reservoir. The free hormone hypothesis derived from now outdated 1970’s pharmacological theory on the mechanism of drug-drug interactions as due to mutual protein binding displacement; however, this theory is long superseded in molecular pharmacology by well-established physiological mechanisms such as cytochrome P450 enzyme induction, drug transporter activity and cognate mechanisms unrelated to binding to circulating proteins (81). As the free and/or bioavailable fractions would also have enhanced access to sites of testosterone inactivation by degradative metabolism that terminates androgen action, the free fractions may equally be considered the most evanescent and least active so that the net biological significance of the free or bioavailable fractions remains unclear and undermines a theoretical basis for the free hormone hypothesis. Furthermore empirical evidence indicates that, rather than being biologically inert, SHBG participates actively in cellular testosterone uptake via specific SHBG membrane receptors, uptake mechanisms and signaling via G protein and cyclic AMP (82-86). These mechanisms include the megalin receptor, a multi-valent low-density lipoprotein endocytic receptor located on cell surface membranes that can mediate receptor-mediated cellular uptake of SHBG loaded with testosterone by endocytosis (87, 88) and might influence tissue androgen action (89, 90). Consequently, lacking a physiological basis for the free hormone hypothesis (91) and with empirical evidence in its favor scarce and speculative, it is refuted by intensive, prospective clinical evaluation (92). Hence, the biological significance of partitioning circulating testosterone into these derived fractions remains to be firmly established and its clinical application is unknown or possibly misleading. Furthermore, direct measurement of free testosterone requires laborious, manual methods only available in research or specialist pathology laboratories. Where available, they are costly and lack any external quality control programs or validated reference ranges. As a result, calculations purporting to replicate dialysis-based measurements are often substituted for direct measurements. These formulae come in two different formats – equilibrium binding equations requiring assumptions on testosterone binding stoichiometry and arbitrary plug-in binding affinity estimates (Sodergard (93), Vermeulen (94), Zakharov (95)) or assumption-free empirical methods (Ly(96, 97), Nanjee-Wheeler (98)) calibrated directly to dialysis-based laboratory measurements. Direct comparison has proven that empirical equations are more accurate compared with laboratory dialysis-based measurements (95, 96, 99, 100). Furthermore, calculations of free testosterone using any formula do not contribute significant to mortality or morbidity prognosis for older men’s health beyond accurate measurement of serum testosterone by liquid chromatography-mass spectrometry (92).

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Are my conversions correct for those studies? It seems HED is animal dose / animal conversion factor.

So for ex in the mice study 10 mg/kg would be a HED of 10/12.3 ~ 0.8 mg/kg?

And in the rat study, the HED would be 10/6.17 ~ 1.6 mg/kg?

So at a human weight of 90kg the rat study equivalent would be a HED of 90*1.6 = 144mg of Test P? But apparently they’re giving that to the rats 3x/week, so accounting for the slightly heavier Test C ester (30% vs 20%) we’re basically talking a 500mg/week equivalent for a 90kg human being?

In the mouse study, they say 10mg/kg for 30 days which makes me think they give them that dose every day, which since the conversion factor is twice that of the rats but there are slightly more than 2x the number of days (7 vs 3), we’re talking about a HED of over 650mg/week.

Am I completely off here?

Also how valid are those weight conversions when it comes to pharmacokinetics between rodents and human beings? How do we know these are valid? It’s not a rhetorical/passive aggressive question, I don’t know much about this stuff and I’m just curious how much evidence there is that we can draw valid cross-species conclusions using those conversion rates. For ex maybe rodents have very low SHBG and therefore their Free T is through the roof compared to most human beings. Do we know whether homeostasis in rodents is expressed by the same ratios between hormones as in human beings?

As an aside, 30 days seems really short for the mice study. I know Test P builds up much faster in the blood but still takes (according to SP) about a week to reach close to 100% concentration levels. That leaves 3 weeks of effects to measure, not really a long term study (not a criticism of your content, just saying I wish they’d run actual long studies because that’s the data we’re desperately missing)

It’s actually a good length because mice have much shorter lifespans. So 30 days represents a bigger portion of their life than it does for a human. It’s why they use mice in the first place. You can’t measure the effects and safety profile of a new, untested drug over the course of two years in a human; with mice you can measure that time frame much more quickly and easily.

That’s a good point, I’m just not sure how much evidence there is that the lifespans and related effects are comparable in a proportional way.

Did I miss something?

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