T Nation

What is TRT and What is NOT TRT

What is TRT
For the curious minds or folks seeking a better understanding, TRT stands for Testosterone Replacement Therapy. The R stands for replacement, not enhancement, or elevation. Sometimes there seems to be some confusion between the TRT and pharma section.

Note, after discussion with @highpull below (thank you), using the word replenishment instead of replacement may remove ambiguity with the term replacement.

The human male on average produces about 6 maybe 7 mg a day of testosterone (https://www.health.harvard.edu/newsletter_article/testosterone_aging_and_the_mind). That’s 42-49 mg of testosterone per week. Testosterone production varies over the course of a day with many studies showing a peak in the morning (say 8 AM) and lull in the evening. Looking deeper:

Hypogonadotropic Hypogonadism (HH) and Gonadotropin Therapy - Endotext - NCBI Bookshelf

In the adult male, LH is secreted in pulses approximately every 2 hours (Fig. 2A) (7). However, considerable variability is observed in LH pulse patterns and there is a wide range of testosterone secretory patterns. Indeed, in 15% of normal men whose hypothalamic-pituitary-gonadal (HPG) axis was examined using frequent blood sampling, serum testosterone levels as low as 3.5 nmol/L were recorded (to convert to ng/dL, multiply by 28.6) following long inter-pulse intervals of LH secretion, although mean testosterone levels remained within the normal range (Fig. 3). This within-patient variation must be considered when interpreting single LH and testosterone measurements obtained during the evaluation of a male with suspected hypogonadism. This variability is particularly important in middle-aged and older men as up to 30% men that are found to have a low testosterone concentration, will have a normal level on repeat testing (8).

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Usually there’s peaks and valleys multiple times per day in LH levels. A normal male can dip to below 300 ng/dL TT over the course of the day.

So with that out of the way, what’s the distribution of testosterone levels in healthy adult males? Here’s a nice summary of the distribution of testosterone levels in healthy males vs age.

A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

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To convert the units on the y-axis to the more typical units (ng/dL, at least in US) multiply by 28.84 (testosterone molecular weight = 288.42 g/mol). So not to bore you, the 99 percentile range works out to 173 (1%) to 1000 ng/dL (99%) for a ~20 year old man. Therefore, only true freaks are walking around with peak testosterone levels above 1000 ng/dL. To put that in perspective, the CDC 99% reference for height in men is about 6’4’’. How many guys on here are 6’4’’ and taller?

Notice you can find all the natural T-Nation members up there in the top right corner with TT of about 50 nmol/L or 1442 ng/dL. :slight_smile:

Some of you may bristle at this reality so let me be a little more generous and call “physiologic” a range from 300 – 1200 ng/dL since I know how many studs we have visiting this forum. Sound fair?

Ok, so now let’s get to the pharmacokinetics of testosterone ester preparations which a lot of guys are using. The plots below were generated assuming testosterone cypionate which has a realistic first order elimination half life of about 4.5 days (see reference below).

Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects

I’m not going to go into the details of apparent/actual metabolic clearance rate of testosterone here as not many people care and only 1 part per million in the world understand it. In case you want more info:

Just realize it (the metabolic clearance rate) controls the dose vs the serum levels of testosterone over time. Insert more math here with SHBG, free T, blah blah.

Here’s the time vs testosterone plot for 70 mg testosterone cypionate (TC) per week (dosing intervals of once per week and twice per week). Wait a few weeks and you reach steady state. TC has a molecular weight (MW) of 412.605 g/mol. Testosterone has MW of 288.42 g/mol. Hence TC is 69.9% testosterone by weight and 70 mg/week of TC is 49 mg/week of testosterone.

To makes things simple I’ve assumed the absorption is very fast and elimination follows first order kinetics (to simplify things a bit but not too simple).

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I tuned the ratio of clearance to volume of distribution to fit my peak and trough data. With 70 mg/week (once weekly injection), my peak is about 930 and trough is 330 ng/dL. Confirmed with blood work. If I inject every 3.5 days, peak is 750 and trough is 450 ng/dL. I am comfortably inside the physiologic range (green shading) for either dosing strategy.

Ok, so how about 160 mg/week (that’s 112 mg of testosterone per week):
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Once again confirmed with blood work, if I inject once per week my peak is 2150 ng/dL and trough is 766 ng/dL. If I inject every 3.5 days (twice weekly) peak goes to 1700 and trough is 1000 ng/dL. Remember the green shaded region is the range I spotted you as “physiologic”. So at either dosing frequency, I am running supraphysiologic for peak and get back into physiologic for trough.

Finally, here’s 120 mg per week of TC (84 mg/week of testosterone).
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Dosing weekly results in running above range for peak. At twice weekly, my peak is right on the edge.

In conclusion, these were results tailored to my volume of distribution and clearance rate. Those two parameters for you will be different. See this paper. Therefore, if you want to run physiologic ranges (which by definition is TRT), you’ll need to map your peak and trough to your dosage and dosing frequency. See for example the exchange here I had with our good friend Danny. He and I have very different clearance. You can see from the plots above that having a trough at 1000 ng/dL when dosing either weekly or biweekly with TC is not TRT and depending on your dosng frequency you may be spending a majority of the time above physiologic range. In my particular case this caused elevation of Hct, higher BP. Upon switching to 70 mg/week of TC and staying in range all of the time, all these issues went away.

So when you read on here that 75-100 week of TC is not enough for TRT, you need to do the work and determine if that is true for you. Just throwing out dosages is meaningless until you experimentally determine your clearance. Good luck and best wishes with your TRT.

For a good example of starting off on a TRT protocol, see this thread. Warms my heart that some people are getting pointed in the right direction when starting TRT.

Postscript: what’s my point here with all this? I hope to define terms and it’s important to know what a term refers to. There’s no judgement on my part for guys who want to run enhanced, but for the new guy coming here seeking education, he should start at minimum effective dose, start low and go slow. He deserves to understand the basics and I know this site wants to get the best information out to guys who are suffering. However, if you need to keep your trough testosterone level at 1,000 ng/dL on weekly or biweekly injection frequency to alleviate symptoms, the vast odds are your problem is not androgen deficiency. I’d love to hear others thoughts and data supported arguments.

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@readalot very good write up. You laid this out very well for most parties ease of understanding. Cheers.

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Thanks for your feedback and taking the time to review. Sometimes you just gotta get it out there.

Admittedly some of your posts are a little complex for me to follow, but I enjoyed this one thoroughly. Someone recently posted about

but that’s not comparable to estered test, however as you pointed out it’s still not close to the average doses prescribed and closer to the <100mg range you posted.

You’re likely to get some pushback but let’s see how this plays out.

It’s the 70 mg/week TC example I gave above. 70 mg/week of TC is 49 mg/week of testosterone (~7 mg daily). TC is 69.9% testosterone by weight.

I am trying to improve my dry communication style so glad to hear it was entertaining and valuable.

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I’ve often heard the same numbers for amount of testosterone a male generates, and it just seems so low. It’s hard to wrap my brain around. If I took 100mg a week of test my peak levels would probably be under 300 total t. I know everyone is different but it’s just wild.

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Perhaps this is why men like once a week dosing. They get tested in trough and likely get a higher prescribed dose than the more frequent pinner. Their average levels are going to be supra if they are just barely in range after a week. Basically, by dosing less frequently, they get more T because of the way the testing protocol is set up to test at trough. When the EOD guy is barely in range, his peak is only a bit higher than range.

Perhaps TRT docs should test at roughly peak and roughly trough for each protocol and use the average of the two for decision making.

Edit: Man reading my own posts makes me understand why I was in the dumb kids English class. At least I can do math I guess.

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Hey, don’t ruin it for those guys, they’ll get less Test!
:wink:

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Same. It’s an engineer thing.

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I am always looking up how to spell words. Often a word that I have looked up many times. I just guess when to use the semi colon.

LOL. I think most people do that, based on how it is and is not used. You are one of the more coherent posters on here, and clarity of communication is more important than punctuation. I think even my English degree, book editor wife will back me up on that.

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This has been true for my experience.

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Thank you!

I completely agree here. I try to be clear, but then I think I go overboard and get a bit verbose (pulled that out of my word holster).

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I’d agree with this too. Get a better idea of your average TT levels instead of peak & trough

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I think we would see more people switch to more frequent pinning if this were the case.

Maybe I am just an odd ball, but when starting I thought about asking for once a week shots, because I figured I would get a higher dose after blood work. Maybe most others aren’t trying to understand the science on TRT in order to get more T?

Exactly this. I did 240mg 1x week TT = 1378ng, clinic doc was fine with that.

175mg dosed daily (25mg daily) TT = > 1500ng, doc is freaking out.

It’s better for me to change my protocol around lab times to get more test, but then the labs don’t show a true picture.

He’ll lower me to 140mg, which in reality is plenty for me as long as I dose daily. But I liked the idea of getting more test Rx to me. I was amassing a nice little stockpile.

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This will be hilarious when my thread and review here will be used by guys to get extra testosterone in their protocol. Truly I have done a great service here for “TRT” patients everywhere.

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What would you consider peak testing time on cyp? I thought peak was like 3 days, and if that’s right isn’t that what most people test at?

That was an excellent writeup. From my perspective, I don’t really care what you call it. I think Testosterone Restoration Therapy is a better way of describing it anyway. Honestly, other than I find it interesting how individuals respond to different levels, and how Xmg puts one at 800 trough and the same dose puts another guy at 1100, I’m not overly concerned with numbers.

The first question I have for patients on follow up is “how are you feeling?” When they say great, I pretty much don’t care about the number, though they are happy to hear about the increase.

I don’t think there is any argument that testosterone levels in men have been declining for several decades. That leads me to put little value in the “range” levels. We take guys with levels of 300, 350, 400, 450, (250-1100 Quest range) whatever, with low testosterone symptoms and give them testosterone, even though they are well within the “range”. So while they are in the physiologic range, we call them low and treat them. Yet, when levels go to 2000 peak and 1000 trough, they are “supra” physiologic?

By the way, I am shocked by the number of 20 and 30 something year old guys who sit across from me next to a beautiful girlfriend and tell me they have no sex drive. And…they talk about it with other guys because after they get results their friends come in too! When I was that age, if any one was like that they sure didn’t talk about it. So, something is going on and it’s not good, but that’s for another discussion.

I guess my point is I’m not overly concerned with the numbers, ranges and whatever is considered physiologic or cycling. I’ll listen to the guys, be flexible with dosing, and get them results.

Yes, this always makes me laugh when I read about the “dialing in,” “steady state,” “fluctuation” and hormones in a “state of chaos” guys. While I fully acknowledge some are overly sensitive to hormones, most are not and feel no different on day 1 than day 6 injecting once a week.

Love this because it brings in many patients. A patient is feeling great, but his doctor wants to screw with his dose because of a lab number. Symptoms, not numbers! If in range 400-450 is not OK, why is out of range 1500 not OK?

By the way, some of the recent discussion here led me to look through some files. This will make some here happy. I do have a guy injecting 80mg once a week with a 280 trough number. He feels great.

If there’s interest, for the numbers guys, maybe I could put together a spread sheet with dosing, total, free, and SHBG levels.

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I would like that. Would be helpful. Put it in a new thread.