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:
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).
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.
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.
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).
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).
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):
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).
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 dosing 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 mg per 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.