Lowering trt dose/ increasing frequency of injections question

[kelj358]

Interesting. Appreciate all of the input gents.

 

[Nik]

Some very rough numbers: Twice-weekly injections might give a 50% drop from peak to trough. EOD probably cuts that to 5-10%. Average serum testosterone levels stay about the same at the same dose. For example: suppose with twice weekly injections total testosterone is dropping from a peak of 1000 ng/dL to a trough of 500 ng/dL. After a switch to EOD you might end up with peaks around 790 ng/dL dropping to troughs around 710. A dose decrease of 20% then yields peaks around 630 ng/dL dropping to troughs around 570.

The dose reduction does make sense, particularly if you are trying to reduce side effects of elevated testosterone. The more frequent injections raise the troughs, as mentioned above, such that you can reduce the overall dose without becoming hypogonadal. In the example above the trough with the lower EOD dosing pattern is still higher than with the higher twice-weekly pattern.

My current protocol is 75 mg per week, which puts my total testosterone at 525 and free testosterone at 158. My SHBG is around the low 20s. The problem is that my hematocrit has reached 53, so according to your calculations, where would I be approximately if I take 32.5 mg twice a week for a total of 65 per week? I hope I can get my hematocrit down

 

[Nik]

Some very rough numbers: Twice-weekly injections might give a 50% drop from peak to trough. EOD probably cuts that to 5-10%. Average serum testosterone levels stay about the same at the same dose. For example: suppose with twice weekly injections total testosterone is dropping from a peak of 1000 ng/dL to a trough of 500 ng/dL. After a switch to EOD you might end up with peaks around 790 ng/dL dropping to troughs around 710. A dose decrease of 20% then yields peaks around 630 ng/dL dropping to troughs around 570.

The dose reduction does make sense, particularly if you are trying to reduce side effects of elevated testosterone. The more frequent injections raise the troughs, as mentioned above, such that you can reduce the overall dose without becoming hypogonadal. In the example above the trough with the lower EOD dosing pattern is still higher than with the higher twice-weekly pattern.

I should clarify that I administer the 75mg once a week.

 

[Vince]

I find it really interesting that members lower their dose to lower their free testosterone and they still have to donate blood.

 

[Willyt]

My current protocol is 75 mg per week, which puts my total testosterone at 525 and free testosterone at 158. My SHBG is around the low 20s. The problem is that my hematocrit has reached 53, so according to your calculations, where would I be approximately if I take 32.5 mg twice a week for a total of 65 per week? I hope I can get my hematocrit down

A popular protocol is 10mg daily subq injections w/ small gauge 5/16 needles (70mg per week). That would certainly blunt your peaks assuming that is what is driving up your hematocrit

 

[Cataceous]

My current protocol is 75 mg per week, which puts my total testosterone at 525 and free testosterone at 158. My SHBG is around the low 20s. The problem is that my hematocrit has reached 53, so according to your calculations, where would I be approximately if I take 32.5 mg twice a week for a total of 65 per week? I hope I can get my hematocrit down

With the caveat that these are very crude estimates based on typical absorption rates and should only be used to get a general sense of things: Your trough testosterone of 525 ng/dL with once-weekly injections means we might estimate your weekly peak total testosterone (TT) as 1,300 ng/dL and your average as 900 ng/dL. Cutting the dose to 65 mg per week reduces the average TT to 780 ng/dL. For twice weekly injections I'll say that the trough is 60% of the peak, which is probably closer to the mark than the 50% I used above. This puts the new peak TT at about 1,000 ng/dL and the new trough at 600 ng/dL.

This could have some effect on hematocrit. However, it's likely these testosterone numbers are still somewhat high relative to your healthy natural numbers, which would limit the reduction.

 

[Nik]

With the caveat that these are very crude estimates based on typical absorption rates and should only be used to get a general sense of things: Your trough testosterone of 525 ng/dL with once-weekly injections means we might estimate your weekly peak total testosterone (TT) as 1,300 ng/dL and your average as 900 ng/dL. Cutting the dose to 65 mg per week reduces the average TT to 780 ng/dL. For twice weekly injections I'll say that the trough is 60% of the peak, which is probably closer to the mark than the 50% I used above. This puts the new peak TT at about 1,000 ng/dL and the new trough at 600 ng/dL.

This could have some effect on hematocrit. However, it's likely these testosterone numbers are still somewhat high relative to your healthy natural numbers, which would limit the reduction.

I appreciate your detailed response. Based on these numbers, I could try reducing to 65 mg once a week. If I'm not mistaken, this would put me at around 400 mg without reaching hypogonadal territory. The fact is that, due to cost, doing it twice a week skyrockets the price, since here testosterone is only sold in ampoules, and it doesn't have a preservative, so the excess is discarded. It's incredible that when I was on 250 mg every 21 days, my hematocrit was at 46, so increasing the frequency, even at therapeutic doses like 75 mg once a week, raised my hematocrit

 

[Cataceous]

I appreciate your detailed response. Based on these numbers, I could try reducing to 65 mg once a week. If I'm not mistaken, this would put me at around 400 mg without reaching hypogonadal territory. The fact is that, due to cost, doing it twice a week skyrockets the price, since here testosterone is only sold in ampoules, and it doesn't have a preservative, so the excess is discarded. It's incredible that when I was on 250 mg every 21 days, my hematocrit was at 46, so increasing the frequency, even at therapeutic doses like 75 mg once a week, raised my hematocrit

Looking back at your posts I see that you use Testoviron. This includes benzyl benzoate, which does have anti-microbial properties, though it's not as effective as benzyl alcohol. It would not be difficult to purchase some benzyl alcohol and sterile vials to convert the ampules to multi-dose vials. I trust you're already using filter needles to remove possible glass fragments?

The response of hematocrit to dose can seem pretty mysterious at times. Not sure how long you were on the 250 mg once every three weeks, but things might have changed as time went on. The long and low trough testosterone levels might also have been a factor in keeping hematocrit in check on that protocol.

 

[Nik]

Looking back at your posts I see that you use Testoviron. This includes benzyl benzoate, which does have anti-microbial properties, though it's not as effective as benzyl alcohol. It would not be difficult to purchase some benzyl alcohol and sterile vials to convert the ampules to multi-dose vials. I trust you're already using filter needles to remove possible glass fragments?

The response of hematocrit to dose can seem pretty mysterious at times. Not sure how long you were on the 250 mg once every three weeks, but things might have changed as time went on. The long and low trough testosterone levels might also have been a factor in keeping hematocrit in check on that protocol.

Well, I was on 250mg every 21 days for a year. The truth is, my hematocrit reacts strangely even after reducing the dose. Unfortunately, in my country, they don't allow the import of benzyl alcohol because it's listed among medical articles, so its entry is prohibited (which is stupid). Would you say 65mg per week would be reasonable? I'm trying to reduce my hematocrit, otherwise I'll have to go back to the rollercoaster of 250mg every 21 days.

 

[Cataceous]

... Unfortunately, in my country, they don't allow the import of benzyl alcohol because it's listed among medical articles, so its entry is prohibited (which is stupid). Would you say 65mg per week would be reasonable? I'm trying to reduce my hematocrit, otherwise I'll have to go back to the rollercoaster of 250mg every 21 days.

I think 65 mg is a reasonable start. Be aware that dose reductions can trigger temporary symptoms of hypogonadism even when levels are adequate. Using proportionality does put total testosterone at weekly troughs in the mid 400s ng/dL with this protocol. As an aside, it is technically more accurate to apply the proportionality to free testosterone than to total; in theory the testosterone dose rate is directly and proportionally driving free testosterone.

Speaking only for myself, and not making a recommendation: Assuming sterile vials are available I would use the ampule contents for two doses. I would be comfortable doing this with subcutaneous administration because of the anti-microbal action of benzyl benzoate, the short 3-4 day period before the second injection, and the relatively low risk of significant harm from subcutaneous infections.

 

[MarcoFL]

I find it really interesting that members lower their dose to lower their free testosterone and they still have to donate blood.

probably not drinking enough water.

 

[Vince]

probably not drinking enough water.

That's probably one of the reasons

 

[Nik]

With the caveat that these are very crude estimates based on typical absorption rates and should only be used to get a general sense of things: Your trough testosterone of 525 ng/dL with once-weekly injections means we might estimate your weekly peak total testosterone (TT) as 1,300 ng/dL and your average as 900 ng/dL. Cutting the dose to 65 mg per week reduces the average TT to 780 ng/dL. For twice weekly injections I'll say that the trough is 60% of the peak, which is probably closer to the mark than the 50% I used above. This puts the new peak TT at about 1,000 ng/dL and the new trough at 600 ng/dL.

This could have some effect on hematocrit. However, it's likely these testosterone numbers are still somewhat high relative to your healthy natural numbers, which would limit the reduction.

I've been racking my brain trying to figure out the differences between a single weekly dose versus splitting the dose into two doses per week. Where would the minimum be if, for example, I were to inject 30mg every 3.5 days for a total of 60mg per week? I'd like to see if my calculations match your answer. Remember that with 75mg once a week I was reaching a minimum of 525ng and a calculated free globulin of 158pg/ml. Here, there's no way to analyze free globulin with equilibrium dialysis.

 

[Phil Goodman]

I've been racking my brain trying to figure out the differences between a single weekly dose versus splitting the dose into two doses per week. Where would the minimum be if, for example, I were to inject 30mg every 3.5 days for a total of 60mg per week? I'd like to see if my calculations match your answer. Remember that with 75mg once a week I was reaching a minimum of 525ng and a calculated free globulin of 158pg/ml. Here, there's no way to analyze free globulin with equilibrium dialysis.

Based on Claude’s calculations the trough would be very comparable. And for extra insight I asked it to do the same thing with peaks, which will show where the benefits would likely come from with regard to lowering hematocrit (hopefully). Feel free to disregard the formulas, you can get everything you need from the explanations.



Using a simplified one-compartment steady-state model, the trough at steady state for a given dosing interval τ is:
Cmin = C0 · e^(-kτ) / (1 - e^(-kτ))
where k = ln(2)/t½ and C0 is proportional to dose.
Let r7 = e^(-7k) (fraction remaining after 7 days), so r3.5 = √r7.
Using your reference point (75mg QW → 525 ng/dL trough) to eliminate Vd, the ratio simplifies to:
Cmin,BIW = 0.4 × 525 × (1 + √r7) / √r7
With testosterone cypionate (t½ ≈ 7 days): r7 = 0.5, so √r7 = 1/√2 ≈ 0.707
Cmin,BIW = 210 × (1 + √2) = 210 × 2.414 ≈ 507 ng/dL
Once weekly: 75mg every 7 days (75mg/week) → Trough ~525 ng/dL, Free T ~158 pg/mL
Twice weekly: 30mg every 3.5 days (60mg/week) → Trough ~507 ng/dL, Free T ~153 pg/mL
Despite cutting the weekly dose by 20% (75 → 60mg), the trough only drops ~3.4% (525 → 507). Splitting the dose shortens the interval enough that levels are topped up before dropping as far, largely compensating for the reduced total dose. Free testosterone tracks nearly proportionally: 158 × (507/525) ≈ 153 pg/mL.


At steady state, the peak is simply:
Cmax,ss = C0 / (1 - e^(-kτ))
And since Cmin = C0 · r / (1 - r), this means:
Cmax = Cmin / r
where r = e^(-kτ) for each respective interval.
Once weekly (75mg, τ = 7 days, r7 = 0.5):
Cmax = 525 / 0.5 = 1050 ng/dL
Peak free T ≈ 158 × (1050/525) = ~316 pg/mL
Twice weekly (30mg, τ = 3.5 days, r3.5 = 0.707):
Cmax = 507 / 0.707 = ~717 ng/dL
Peak free T ≈ 153 × (717/507) = ~216 pg/mL
Once weekly: Peak ~1050 ng/dL, Trough ~525 ng/dL, Peak:Trough ratio = 2.0:1
Twice weekly: Peak ~717 ng/dL, Trough ~507 ng/dL, Peak:Trough ratio = 1.41:1
This is where split dosing shows its biggest advantage. The trough barely moves (525 → 507), but the peak drops dramatically (1050 → 717), cutting the peak-to-trough swing nearly in half. The 1.41:1 ratio is exactly √2:1, which is the mathematical consequence of the dosing interval being exactly half the half-life. The free T estimate at peak assumes proportional scaling — in reality it would be slightly higher than shown due to SHBG saturation at elevated total T levels, so 216 pg/mL is a modest underestimate.

 

[Nik]

Based on Claude’s calculations the trough would be very comparable. And for extra insight I asked it to do the same thing with peaks, which will show where the benefits would likely come from with regard to lowering hematocrit (hopefully). Feel free to disregard the formulas, you can get everything you need from the explanations.



Using a simplified one-compartment steady-state model, the trough at steady state for a given dosing interval τ is:
Cmin = C0 · e^(-kτ) / (1 - e^(-kτ))
where k = ln(2)/t½ and C0 is proportional to dose.
Let r7 = e^(-7k) (fraction remaining after 7 days), so r3.5 = √r7.
Using your reference point (75mg QW → 525 ng/dL trough) to eliminate Vd, the ratio simplifies to:
Cmin,BIW = 0.4 × 525 × (1 + √r7) / √r7
With testosterone cypionate (t½ ≈ 7 days): r7 = 0.5, so √r7 = 1/√2 ≈ 0.707
Cmin,BIW = 210 × (1 + √2) = 210 × 2.414 ≈ 507 ng/dL
Once weekly: 75mg every 7 days (75mg/week) → Trough ~525 ng/dL, Free T ~158 pg/mL
Twice weekly: 30mg every 3.5 days (60mg/week) → Trough ~507 ng/dL, Free T ~153 pg/mL
Despite cutting the weekly dose by 20% (75 → 60mg), the trough only drops ~3.4% (525 → 507). Splitting the dose shortens the interval enough that levels are topped up before dropping as far, largely compensating for the reduced total dose. Free testosterone tracks nearly proportionally: 158 × (507/525) ≈ 153 pg/mL.


At steady state, the peak is simply:
Cmax,ss = C0 / (1 - e^(-kτ))
And since Cmin = C0 · r / (1 - r), this means:
Cmax = Cmin / r
where r = e^(-kτ) for each respective interval.
Once weekly (75mg, τ = 7 days, r7 = 0.5):
Cmax = 525 / 0.5 = 1050 ng/dL
Peak free T ≈ 158 × (1050/525) = ~316 pg/mL
Twice weekly (30mg, τ = 3.5 days, r3.5 = 0.707):
Cmax = 507 / 0.707 = ~717 ng/dL
Peak free T ≈ 153 × (717/507) = ~216 pg/mL
Once weekly: Peak ~1050 ng/dL, Trough ~525 ng/dL, Peak:Trough ratio = 2.0:1
Twice weekly: Peak ~717 ng/dL, Trough ~507 ng/dL, Peak:Trough ratio = 1.41:1
This is where split dosing shows its biggest advantage. The trough barely moves (525 → 507), but the peak drops dramatically (1050 → 717), cutting the peak-to-trough swing nearly in half. The 1.41:1 ratio is exactly √2:1, which is the mathematical consequence of the dosing interval being exactly half the half-life. The free T estimate at peak assumes proportional scaling — in reality it would be slightly higher than shown due to SHBG saturation at elevated total T levels, so 216 pg/mL is a modest underestimate.

Well, first of all, thank you very much for your detailed explanation. It's incredible how by reducing from 75mg to 60mg by dividing the dose, I can obtain almost the same levels of free testosterone. I think 60mg divided into two doses could be a reasonable amount in my case, given the levels I achieved with 75mg once a week. I will update this post in six weeks. Do you think I will be very close to my ideal dose?

30mg every 3.5 days. I hope that by reducing and dividing the dose, my hematocrit can be controlled.

 

[Phil Goodman]

Well, first of all, thank you very much for your detailed explanation. It's incredible how by reducing from 75mg to 60mg by dividing the dose, I can obtain almost the same levels of free testosterone. I think 60mg divided into two doses could be a reasonable amount in my case, given the levels I achieved with 75mg once a week. I will update this post in six weeks. Do you think I will be very close to my ideal dose?

30mg every 3.5 days. I hope that by reducing and dividing the dose, my hematocrit can be controlled.

No problem. But you won’t have almost the same average free testosterone, it’s just that your trough will be very close to the same level because you are clipping the trough as well as the peak. Your average will be reduced by basically the same percentage as your dose, it’s just that you’ll be cutting it off of the peak instead of the trough.

With regard to hematocrit, most if not all of the increase will seen within the first six months, so it’s possible you’ve already reached that point and that further increases would be minimal to non-existent. The average increase from injectable test is around 4 points, but obviously that is affected by dosage, frequency, genetics, and other variables. It’s also just a snapshot in time and can change by a few points just from simple things like hydration at time of testing. That being said, if you’ve already settled in at your new dose then just stick with it and see what things look like for you your next bloodwork. If you feel as good or better then obviously the lower dose would be preferable for numerous reasons. So again at this point I say just stick with and see how you feel as well as what your bloodwork looks like next time.