The loading dose for testosterone undecanoate is used to shorten the time required to reach steady-state levels due to its extremely long half-life.
You can plot the pharmacokinetics via the various steroidcalc apps available and see that the loading dose never produces a mg released p/d of testosterone above that seen at steady state — it only serves to reduce the time taken to reach steady state.
Accordingly, it's inappropriate to factor the loading dose(s) into your calculation of the average testosterone dose per day.
750mg testosterone undecanoate IM every ten weeks = ~ 10 mg testosterone undecanoate per day.
10mg testosterone undecanoate provides ~ 6mg of actual testosterone after the weight of the ester has been accounted for (your calculations did not factor in ester weight and assumed that 1mg testosterone undecanoate = 1 mg testosterone, which it does not; testosterone undecanoate is approximately 63.15% testosterone by weight).
There is ample data suggesting that young, healthy males can produce up to 8 - 10mg of testosterone daily.
The only study to ever show an increased risk of ASCVD from testosterone replacement was a retrospective analysis of an insurance database that did not even verify whether or not the testosterone was taken, only that it had been, at some point, prescribed at least once. Further, it also compared rates against the general population, not men with low testosterone who went untreated.
Accordingly, if a significant proportion of those men did not start or continue treatment after the first prescription (which is very common when you look at the data on long-term adherence to TRT), all that data shows is that men with low testosterone experience ASCVD at a greater rate than men with normal serum levels, something we already know.
The rest of the data on the topic all show an improvement in cardiovascular health when compared to men with untreated hypogonadism.
With all of the above considered, I'm not sure how one can argue that the way in which testosterone is currently being administered is 'incorrect' or 'unphysiological' given it largely matches endogenous production and the interventional data in humans shows universal benefit.
These are all the same critiques of TRT presented within the Ray Peat community: critiques that don't hold up to scrutiny nor reflect the real-world clinical outcomes seen in actual men on TRT.
Yes, but the dose is given ALL AT ONCE. This I think is why there are indeed good studies showing a heightened risk of morbidity, from TRT. Because the dose that is 2 or 4 weeks is a VERY LARGE DOSE when delivered all at the same time.
And, you are incorrect about T production for a healthy male. I cited my study and I have others, that show 4 or 5mg per day is actually the number.
The loading dose for testosterone undecanoate is used to shorten the time required to reach steady-state levels due to its extremely long half-life.
You can plot the pharmacokinetics via the various steroidcalc apps available and see that the loading dose never produces a mg released p/d of testosterone above that seen at steady state — it only serves to reduce the time taken to reach steady state.
Accordingly, it's inappropriate to factor the loading dose(s) into your calculation of the average testosterone dose per day.
750mg testosterone undecanoate IM every ten weeks = ~ 10 mg testosterone undecanoate per day.
10mg testosterone undecanoate provides ~ 6mg of actual testosterone after the weight of the ester has been accounted for (your calculations did not factor in ester weight and assumed that 1mg testosterone undecanoate = 1 mg testosterone, which it does not; testosterone undecanoate is approximately 63.15% testosterone by weight).
There is ample data suggesting that young, healthy males can produce up to 8 - 10mg of testosterone daily.
The only study to ever show an increased risk of ASCVD from testosterone replacement was a retrospective analysis of an insurance database that did not even verify whether or not the testosterone was taken, only that it had been, at some point, prescribed at least once. Further, it also compared rates against the general population, not men with low testosterone who went untreated.
Accordingly, if a significant proportion of those men did not start or continue treatment after the first prescription (which is very common when you look at the data on long-term adherence to TRT), all that data shows is that men with low testosterone experience ASCVD at a greater rate than men with normal serum levels, something we already know.
The rest of the data on the topic all show an improvement in cardiovascular health when compared to men with untreated hypogonadism.
With all of the above considered, I'm not sure how one can argue that the way in which testosterone is currently being administered is 'incorrect' or 'unphysiological' given it largely matches endogenous production and the interventional data in humans shows universal benefit.
These are all the same critiques of TRT presented within the Ray Peat community: critiques that don't hold up to scrutiny nor reflect the real-world clinical outcomes seen in actual men on TRT.
Yes, but the dose is given ALL AT ONCE. This I think is why there are indeed good studies showing a heightened risk of morbidity, from TRT. Because the dose that is 2 or 4 weeks is a VERY LARGE DOSE when delivered all at the same time.
And, you are incorrect about T production for a healthy male. I cited my study and I have others, that show 4 or 5mg per day is actually the number.
Thank you for posting and thank you for reading.