What kind of levels to expect from 100mg weekly

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alextripp

New Member
I'm a new to this entire scene, started with levels of around 320, age 40, doctor started me on 100mg once a week. Curious on what type of levels I should expect to see from this?

Thanks
 
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Goel

Member
I also started at 100mg once/week but everybody's response is different so your levels won't necessarily be like mine. As someone who's 3 months into this process, the key is to be patient and adjust your expectations - it's a process not a light switch (much as I'd like it to be!). Also, to a large extent it's more about how you feel subjectively compared to where you began on this path than chasing "levels".
 

madman

Super Moderator
I'm a new to this entire scene, started with levels of around 320, age 40, doctor started me on 100mg once a week. Curious on what type of levels I should expect to see from this?

Thanks


No one can say for sure as many factors come into play (dose T/SHBG level/ sensitivity of the AR, polymorphism of the AR and CAG repeat length (long/short), body weight, injection frequency).

Although TT is important to know I would be much more concerned with what FT level is achieved on such protocol (dose of T/injection frequency).

Too many get caught up on where TT levels will end up when FT is what truly matters as it is the active unbound fraction of testosterone responsible for the positive effects.

Keep in mind that when first starting trt not only will your hpta be shutting down (within 2-6 weeks) but your testosterone levels will be rising and in flux during the weeks leading up until blood levels stabilize (4-6 weeks).

During this critical time, there is a lot going on, and depending on the individual many will experience what we call the honeymoon period where one can feel euphoric with an increase in libido due to androgen levels rising/increase in dopamine and this is usually temporary and short-lived as the body will eventually adapt.

It is also common for many to experience bumps (ups/downs) along the way as T levels are in flux.

Many end up making the mistake of gauging how they feel during this time which can be very misleading as blood levels will not stabilize until 4-6 weeks in and even then once levels have stabilized it can take 2-3 months for the body to fully adapt to those new levels and this is the critical time period when one should truly gauge how they feel regarding relief/improvement of low-t symptoms and overall well-being.

Patience is key.

Blood work should be done at 6 weeks to not only see where said protocol (dose T/injection frequency) puts your TT/FT/e2 levels but also to make sure blood markers remain healthy as we want to avoid/minimize any potential side-effects long-term.

Blood work should be done at trough (lowest point) as we want to know where T levels sit as too low or too high could negate the beneficial effects of having healthy FT levels.

Seeing as you were started on once-weekly injections (100 mg/week) then if you are injecting Monday morning at 9 am then blood work would be done the following Monday morning before your 9 am injection as this would be your TRUE TROUGH (lowest point) blood levels.

When injecting larger doses of T once weekly levels will start rising within 2 hrs post-injection and peak 8-12 hrs as they will stay elevated during the first few days and decline to much lower levels (true trough) come weeks end.

The main downfall of injecting larger doses of T once weekly is that there can be a large difference in peak--->trough and blood levels will not be as stable throughout the week which in many cases can have a negative impact on energy/mood/libido/erectile function/recovery and overall well-being.

You would most likely do much better splitting the 100 mg/week dose into twice-weekly injections (50 mg every 3.5 days) and depending on SHBG may even need to inject more frequently as in EOD or daily as this will have a big impact on not only clipping the peak--->trough but result in much more stable levels throughout the week.

Stick to your protocol for the next 6 weeks then get blood work done and depending on labs and where your levels sit you may very well need a dose adjustment but this comes down to where your TT/FT levels sit/symptom relief (mind you 6 weeks is far too early to truly gauge this) if levels truly are still too low and you feel horrible at the 6-week mark than a dose adjustment will be needed let alone injection frequency may be tweaked.
 

alextripp

New Member
Very informative response, thanks so much. So over the next 6 to 8 weeks I could expect to see an improvement, is that due to the T progressively increasing? I asked my doctor about 2x a week, he suggested we stay at one a week to see how I feel post 6 weeks

Also, would you say 100mg is a good starting place? I was told it's Test Cypionate
 

madman

Super Moderator
Very informative response, thanks so much. So over the next 6 to 8 weeks I could expect to see an improvement, is that due to the T progressively increasing? I asked my doctor about 2x a week, he suggested we stay at one a week to see how I feel post 6 weeks

Also, would you say 100mg is a good starting place? I was told it's Test Cypionate

Yes, you should definitely notice improvements in energy/mood/libido/erectile function/recovery and overall well being but to what degree can vary depending on how the individual reacts let alone what TT/FT level among other hormones is achieved once blood levels stabilize but I would not get caught up in this as again the first 6 weeks can be very misleading.

Once levels stabilize it will take 2-3 months for the body to adapt to those new levels.

Again patience is key.

I would prefer to split the 100 mg/week injection twice weekly (50 mg every 3.5 days) as you will clip the peak--->trough and blood levels will be more stable throughout the week.


 

Cataceous

Super Moderator
Just as an academic exercise it's interesting to make a rough prediction of the average serum testosterone levels an average young man would achieve with 100 mg testosterone cypionate per week. Here are the assumptions:
  • Average natural testosterone production: 6-7 mg
  • Average peak testosterone 600-700 ng/dL
  • Diurnal variation off of peak: 40%
  • No change in albumin or SHBG
We'll just use 6.5 mg natural T production resulting in 650 ng/dL TT. So weekly natural production is 45.5 mg T, which is the amount contained in 65 mg T cypionate. We convert from peak to average serum testosterone by multiplying by 80%: 520 ng/dL. With unchanging albumin and SHBG we'll assume that total testosterone is linear with dose. Therefore:

TT(avg-100mg/w) = 520 ng/dL * 100 mg TC / 65 mg TC = 800 ng/dL

This is the predicted average serum level, meaning it's what would be measured if the guy were injecting frequently, e.g. daily and maybe even EOD. But suppose he starts out with injections once a week and has typical absorption for cypionate, meaning a 5-day half-life. Then he measures a trough level of about 450 ng/dL. We see this kind of thing all the time. Guys measure a lowish trough like this and want to greatly increase the dose. But the post-injection peak in testosterone is ignored. In this example it is more like 1,150 ng/dL.

It wouldn't be uncommon in a case like this for the dose to be increased by 50% to raise the trough measurement to healthy-young-man levels of 600-700 ng/dL. Unseen is that the average serum testosterone jumps to 1,200 ng/dL and the peak rises to over 1,700. Then people are surprised when all the side effects kick in: HCT, E2 issues, DHT issues, etc.
 

Acer97

Member
I'm a new to this entire scene, started with levels of around 320, age 40, doctor started me on 100mg once a week. Curious on what type of levels I should expect to see from this?

Thanks
Im on 100mg once a week my levels 2 days after are 1050 4 day’s after are 850 and 7 days after are 500
 

Cataceous

Super Moderator
Im on 100mg once a week my levels 2 days after are 1050 4 day’s after are 850 and 7 days after are 500
It's interesting to get data like this to see what kind of apparent half-life it has. In your case it is 4.9 days, with a predicted peak testosterone around 1,300-1,400 ng/dL.
Response to Cypionate.JPG
 
T

tareload

Guest
It's interesting to get data like this to see what kind of apparent half-life it has. In your case it is 4.9 days, with a predicted peak testosterone around 1,300-1,400 ng/dL.
View attachment 11474

EDIT: my apology, I forgot to dedicate this analysis to @Nelson Vergel, @madman, @Cataceous for all the efforts you guys put in on here.


Cool data, thanks guys. I had been using a zero compartment model (was being lazy) but have moved over to a one-compartment model with first order absorption and linear elimination based on this work:

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

Assuming @Acer97 is completely shutdown and fitting the data points to give minimum error, here's the zero-compartment model with central volume of distribution set at 10.2 kL (V/F = 14.6 kL with F = 0.7) where Cmax is immediate (Tmax = 0) followed by elimination:

1604595057709.png




1604595219745.png


So fitting the data I get about 4.6% error and an estimated elimination half life of 4.5 days:

1604601389052.png


Using a one-compartment model:

1604595427443.png


1604595523573.png


Using this approach I get about 1.5% error with estimated absorption half life of 16 hours and elimination half life of 4 days:

1604601405771.png



Calculated Tmax is 49.5 hours.

1604596108034.png


Here's both models along with the three data points. I just took the period from 28 to 35 days in the model to compare against the data since by this point steady-state is reached.

1604595692361.png


Very big difference in predicted peak and AUC between the two approaches.

Going back to the paper above, really interesting to see the diversity of estimated absorption and elimination rate constants which when taken together will drastically swing the estimated Tmax:
1604595880537.png
 
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Cataceous

Super Moderator
Cool data, thanks guys. I had been using a zero compartment model (was being lazy) but have moved over to a one-compartment model with first order absorption and linear elimination based on this work:
...
Maybe you can explain this possible discrepancy. Assume first order absorption and first order utilization, which results in the usual bi-exponential curve. The problem is that with the typical measured parameters the time to achieve peak level should be fairly insensitive to the absorption constant, because it's so much longer than the consumption constant. For example, the half-life of testosterone in serum is on the order of minutes, while the half-life of testosterone cypionate is more like five days. These values result in a very early post-injection peak, at most a few hours. Anecdotally I do see this fast rise with testosterone propionate. But the situation with cypionate is less clear—your data are showing a couple days to peak, which seems long.
 
T

tareload

Guest
Maybe you can explain this possible discrepancy. Assume first order absorption and first order utilization, which results in the usual bi-exponential curve. The problem is that with the typical measured parameters the time to achieve peak level should be fairly insensitive to the absorption constant, because it's so much longer than the consumption constant. For example, the half-life of testosterone in serum is on the order of minutes, while the half-life of testosterone cypionate is more like five days. These values result in a very early post-injection peak, at most a few hours. Anecdotally I do see this fast rise with testosterone propionate. But the situation with cypionate is less clear—your data are showing a couple days to peak, which seems long.

From the paper I cited above:

Following the depot administration of TC, the PKs of tT were satisfactorily described by the one‐compartmental model with first‐order absorption. The limited number of samples in the absorption phase (1–2 samples per subject) prevents using a more plausible absorption model for the high lipophilicity of testosterone in an oil base and administered i.m., such as a mixed zero‐order and first‐order model with lag time.16 This could lead to flip‐flop PKs and can cause difficulties in estimation and interpretation of PK parameters.17 The half‐life of testosterone undecanoate (TU) following oral administration is around 150 minutes,18 which is very different from the half‐life estimate of 21–34 days following the i.m. injection of TU reported by Behre et al.19 The large difference in half‐lives of TU between oral and i.m. formulation suggests that flip‐flop PKs are occurring with testosterone esters, which is also reported in the published literature20 and for the i.m. injection of nandrolone.21 The i.m. injection of TC is also likely to have flip‐flop kinetics, in such a scenario, diffusion and release from an oily depot site is the rate‐limiting step to systemic availability.

So my takeaway is the empirically-fit half lives for "absorption" and "elimination" are most likely co-variant and as you state much longer than the actual elimination half life of testosterone in the body. You've got the surface area to volume ratio of the oily depot, hydrolysis of the ester, sub-Q vs IM, whether the patient pushes on the injection site with their finger after injection (changes the surface area to volume ratio).

As an academic exercise you can plug different absorption half life inputs into the following equation for tmax with an apparent elimination half life of 4 days (I vary the apparent absorption half life from 1 to 16 hr in this example):
1604679711908.png


Typical conversion of t0.5 to rate constant K by

t0.5 = ln(2) / K

1604679912269.png


Given the flip flop kinetics, the actual or true elimination kinetics never enter into the parameters that properly fit the transient data. The calculated tmax is quite sensitive to the apparent absorption half life (even though it's most likely strongly correlated with apparent elimination half life).

I know in the literature I've scanned the tmax values for TC/TE done IM and sub-Q, and they vary from 16 to 48 hours. Using the values in the table I highlighted in the last post (bootstrap), you can observe large variation in tmax from less than 24 hours to 60 hours.

1604682202197.png
 
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T

tareload

Guest
@Cataceous, reaching way back, these hypo guys from 1982 have an average fit tmax of about 27 hrs:
1604684468680.png


1604684533025.png



1604684489400.png




Digitizing the hypo guys and fitting the data with the 1 compartment:

1604684587042.png


I get an apparent elimination half life of 6.8 days, apparent absorption half life of 5.3 hr and calculated tmax of 27 hours. So quite a diversity among the literature data. I picked the hypo guys here to remove the LH/endogenous T effect on the PK parameter fitting.
 

Cataceous

Super Moderator
...
I get an apparent elimination half life of 6.8 days, apparent absorption half life of 5.3 hr and calculated tmax of 27 hours. So quite a diversity among the literature data. ...
Indeed, the earlier Nieschlag data, also using hypogonadal men, shows a peak for enanthate that's under 14 hours.

Assuming the literature is correct in saying the half-life of testosterone in plasma is around 10-100 minutes, what else is going on to delay time to peak serum levels?
 
T

tareload

Guest
Indeed, the earlier Nieschlag data, also using hypogonadal men, shows a peak for enanthate that's under 14 hours.

Assuming the literature is correct in saying the half-life of testosterone in plasma is around 10-100 minutes, what else is going on to delay time to peak serum levels?

So my takeaway is the empirically-fit half lives for "absorption" and "elimination" are most likely co-variant and as you state much longer than the actual elimination half life of testosterone in the body. You've got the surface area to volume ratio of the oily depot, hydrolysis of the ester, sub-Q vs IM, whether the patient pushes on the injection site with their finger after injection (changes the surface area to volume ratio).

Also pinged you on @madman 's post on the oil depot diffusion. Those site of injection plots are really compelling.
 
T

tareload

Guest
Indeed, the earlier Nieschlag data, also using hypogonadal men, shows a peak for enanthate that's under 14 hours.

Assuming the literature is correct in saying the half-life of testosterone in plasma is around 10-100 minutes, what else is going on to delay time to peak serum levels?

I went back to original Nieschlag paper (1976), but injection site was not disclosed. They state IM injection. So now we will need to keep track of injection site, lymphatic drainage of the test subject in addition to dose and dose frequency when analyzing the PK.
 

URUGUAYO

New Member
Just as an academic exercise it's interesting to make a rough prediction of the average serum testosterone levels an average young man would achieve with 100 mg testosterone cypionate per week. Here are the assumptions:
  • Average natural testosterone production: 6-7 mg
  • Average peak testosterone 600-700 ng/dL
  • Diurnal variation off of peak: 40%
  • No change in albumin or SHBG
We'll just use 6.5 mg natural T production resulting in 650 ng/dL TT. So weekly natural production is 45.5 mg T, which is the amount contained in 65 mg T cypionate. We convert from peak to average serum testosterone by multiplying by 80%: 520 ng/dL. With unchanging albumin and SHBG we'll assume that total testosterone is linear with dose. Therefore:

TT(avg-100mg/w) = 520 ng/dL * 100 mg TC / 65 mg TC = 800 ng/dL

This is the predicted average serum level, meaning it's what would be measured if the guy were injecting frequently, e.g. daily and maybe even EOD. But suppose he starts out with injections once a week and has typical absorption for cypionate, meaning a 5-day half-life. Then he measures a trough level of about 450 ng/dL. We see this kind of thing all the time. Guys measure a lowish trough like this and want to greatly increase the dose. But the post-injection peak in testosterone is ignored. In this example it is more like 1,150 ng/dL.

No sería raro en un caso como este que la dosis se incrementara en un 50% para elevar la medición mínima a niveles de hombres jóvenes sanos de 600-700 ng / dL. No se ve que la testosterona sérica promedio salta a 1.200 ng / dL y el pico se eleva a más de 1.700. Luego, la gente se sorprende cuando aparecen todos los efectos secundarios: HCT, problemas de E2, problemas de DHT, etc.
ME INTERSA, Ejemplo... mi análisis dice 450 n/dl.... cuanta enantato de testosterona debería inyectarme, para tener 880 ng/dl. ????
 

Cataceous

Super Moderator
ME INTERSA, Ejemplo... mi análisis dice 450 n/dl.... cuanta enantato de testosterona debería inyectarme, para tener 880 ng/dl. ????
I AM INTERESTED, Example ... my analysis says 450 n / dl .... how much testosterone enanthate should I inject, to have 880 ng / dl. ????
It's not possible to know without more information. If you were the theoretical "average young man" discussed in my example then it would take 107 mg of testosterone enanthate. But you are a unique individual, which means that only by injecting testosterone and getting lab work will you find your response to various doses.
 
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