ABSORPTION OF TESTOSTERONE CREAM VIA SCROTAL DELIVERY (2018)

ABSTRACT

Transdermal testosterone has been used for years to treat patients with low testosterone symptoms. Clinically, we have monitored patients to evaluate results of testosterone absorption via blood serum concentrations. The data on multiple time points to determine trough and peak concentrations is lacking in the literature. In this case study, we demonstrate the absorption of testosterone cream via scrotal delivery. The data suggests that after application therapeutic levels are reached with concentrations of (1204.7 ng/dL) within two hours. Additionally, consistent concentrations (1320.6 ng/dL) remain beyond six hours. To our knowledge, this is the first study to collect and measure multiple time points for testosterone via transdermal delivery. The research indicates that testosterone via transdermal delivery is an excellent method to achieve therapeutic concentrations of testosterone. Most importantly, the patient’s symptoms resolved without side effects.




Because of the first-pass effect, testosterone is not absorbed well orally. Testosterone was thus originally delivered either compressed into subcutaneous pellets or the oral form of methyltestosterone. Methyltestosterone doses high enough to achieve therapeutic levels in men can cause toxic liver side effects. In the 1950s, injectable testosterone enanthate became the preferred therapeutic modality and, later, testosterone cypionate. Implantable pellets require an expensive and invasive office procedure by a specially trained clinician,1 and the concern of infection post-implant is a valid one. After the pellets are inserted, it is nearly impossible to remove the pellets. If the correct dose is not achieved the first time, it is 3 months to 6 months before the next scheduled dose. This can lead to problems with overdosing (side effects) or under-dosing (no optimal effectiveness). Injections can lead to inconsistent levels when dosed every 3 weeks, leading to side effects and/or a lack of therapeutic effect. Injections require a needle, and many patients are not comfortable with administering injections. Options include a visit to a clinician every 3 weeks to receive the injection, which is expensive and time-consuming, or they have someone else administer the injection. Needle disposal is also a problem and an extra expense. In 1992, there was a postulation that therapeutic levels could be achieved via transdermal delivery. Skin patches followed, and, finally, in 2000, transdermal testosterone gels became available.2 Questions remained regarding absorption of transdermal testosterone.3-7 Proper dosing and the maintenance of consistent therapeutic levels of testosterone have not been established. The frequency of dosing, the proper timing of blood draws, and interpretation of those results have not been demonstrated (to our knowledge).

*In this case study, we propose to demonstrate how topical testosterone cream can be used scrotally to deliver therapeutic serum levels.





METHODOLOGY

The testosterone cream was compounded at a concentration via an electronic mortar and pestle, a process that has been verified to ensure adequate mixing. The compounded cream was delivered via a Topi-Pump (Topi-Pump, Lucedale, Mississippi). Each pump delivered 200 mg of testosterone (1 mL). The pump was calibrated to ensure consistent delivery of testosterone. The cream base used was VersaBase (Professional Compounding Centers of America, Houston, Texas).




DISCUSSION

The patient in this case study was a white male in his mid-40s who was experiencing low testosterone symptoms that are typical in this age group, including:

• Decreased libido
• Erectile dysfunction
• Lethargy
• Loss of lean body mass
• Weight gain around the mid-section


Under the advice of a physician, the patient began testosterone therapy. Efforts were undertaken to optimize the dose and application of the testosterone cream. Since the patient had been on a previous 1-year testosterone treatment, the patient was provided the following instructions before beginning the new testosterone therapy:

• Shower the night before the first study application

• Scrub the scrotum and perineum vigorously with warm water and soap to remove any residual testosterone cream

• Apply one pump of a 200-mg dose of the compounded testosterone preparation to the lower scrotum and perineum and, using two fingers, rub the preparation onto the skin to obtain a chalky residue

• Apply the excess cream that remained on his fingers to the upper right inner thigh

• Wash hands with warm soapy water after the application to avoid any possible contamination during sample collection


Per instructions at Spectracell Laboratories (Houston, Texas), blood samples were drawn into a vacuum-sealed vial using a venous blood draw. Timepoints of approximately 0, 1 hour, two hours, and six hours were collected (see results for exact time points). Samples were centrifuged at 3000 rpm for 15 minutes before being placed on ice and shipped to Spectracell Laboratories for further processing and testing of testosterone levels.




RESULTS

*Figure 1 shows the concentration profile in blood serum after administration of a 200-mg dose of testosterone via Topi-Pump and VersaBase

As shown in Figure 1, therapeutic levels were reached at 116 minutes and remained maintained to beyond 346 minutes. Further evidence (unpublished internal data) suggests therapeutic concentrations (>1100 ng/dL) at up to 24 hours. More research is needed to confirm these concentrations. Most importantly, the patient’s low-testosterone symptoms resolved without adverse effects from the therapy.




CONCLUSION

In this study, we demonstrated that with the application of testosterone, adequate absorption occurred to achieve consistent and therapeutic concentrations via scrotal delivery. This data shows the effectiveness of testosterone transdermal delivery with VersaBase cream. In the future, we would like to study dose “proportionality,” further time points past six hours, and how different application sites affect absorption.

FIGURE 1. CONCENTRATION PROFILE IN BLOOD SERUM AFTER ADMINISTRATION OF A 200-MG DOSE OF TESTOSTERONE VIA TOPI-PUMP AND VERSABASE.

Old thread @madman @Cataceous — I’m reading the studies I’m doing the math but need some confirmation or experience: eg. Cream containing 10mg T applied to scrotum.
What % is absorbed and bioavailable? How many mg of T is that equivalent to comparing to an injection once ester component if factored in?

Just trying to get an idea what’s happening. Need labs but expensive. Will get soon.
Hcg alone tt was 560s ft 133. But want to use low dose cream to augment.

Just a bit neurotic and want to understand how much t is getting in my system with each dose of cream.

Thank u

Scrotal absorption is variable, depending on the individual, the carrier, etc. I recall some research finding that absorption can be upwards of 60%, which is quite high compared to what's possible at other locations. Virtually all that gets absorbed is bioavailable.

Suppose you actually achieve 60% absorption via testosterone cream applied to the scrotum. Then you're getting 6 mg of testosterone from the 10 mg in the cream. To compare to injections, consider that testosterone cypionate is 70% testosterone. Thus 6 mg of testosterone is—eventually—absorbed after injecting about 8.6 mg of testosterone cypionate. If you're talking about daily doses then the cream usage could be like injecting an extra 60 mg of TC per week. However, another feature of scrotal application is the very high rate of conversion to DHT. This difference may confound attempts to make a direct comparison to injections.

I've been looking into the T cream for the last couple of months. I've gathered information here and there, but there are a couple of things I don't fully understand.

1. How exactly does half-life with cream work? With injections it's simple, you inject it and the time starts ticking, but with things like creams it's not as clear. If I understand correctly, creams, gels, etc., use Testosterone without an ester. Testosterone has a half life of 2-4 hours, however we likely have to factor in the absorption time, as I'm guessing it's not instant, but takes several hours. So you're not getting all of the T in one go, like with injections, but you're absorbing it through, let's say, 4 hours. Essentially you don't have one clear half life, but rather multiple of them, until you "fully" absorb it. This would explain why the creams work for a longer time and elevated levels of serum T are noticed at 6 and even 16 hour mark, as noted in this and another article.
2. I'm also interested on how the absorption itself works. In most cases, men use 10% or 20% T cream, that is 100mg/ml or 200mg/ml of T. The protocols that are most common are 1-2ml per application, applied 1-2 times a day. This means that the actual amount of T applied is between 100-400mg per day. In terms of injections this would be a massive dose, but for the cream it isn't. Obviously people aren't taking 200mg of cream per day and getting a 60% absorption. From my research it seems like the T creams only have roughly 10% of bio-available T, which would in the case of 200mg per day, mean that only 20mg of that can be used by the body. Then if we factor in the scrotal application, let's say 60% absorption as you mentioned, that would essentially mean that roughly only 12mg of T is actually then used by the body. Is this correct?
3. Finally, it seems like most of the T creams use T without an ester, but why isn't Test P used? Wouldn't this be better to follow the circadian rhythm, as the half life is longer? If the first point is correct, then in the case of Test P, the "half-life" would get "extended" maybe from 20 hours to, let's say, 30. In this case the peaks and valleys might not be as sharp, but still good enough to get the effects from following the natural rhythm. With T without an ester it seems to me that there should be quite a significant serum T drop after the 16 hour mark or so, especially if you're applying once a day.

ziegen said:

How exactly does half-life with cream work?

Click to expand...

t-max 2 hours, half-life 16 hours (this info from the scrotal pharmacokinetics study with some minor extrapolation to determine half-life). This means 18 hours after application you should have half the serum testosterone levels that you had at the 2 hour peak. Serum DHT and E2 behave differently - their tmax lags behind by a couple more hours and they stay inexplicably elevated at a sort of plateau while testosterone drops.

ziegen said:

I'm also interested on how the absorption itself works. In most cases, men use 10% or 20% T cream, that is 100mg/ml or 200mg/ml of T. The protocols that are most common are 1-2ml per application, applied 1-2 times a day. This means that the actual amount of T applied is between 100-400mg per day. In terms of injections this would be a massive dose, but for the cream it isn't. Obviously people aren't taking 200mg of cream per day and getting a 60% absorption. From my research it seems like the T creams only have roughly 10% of bio-available T, which would in the case of 200mg per day, mean that only 20mg of that can be used by the body. Then if we factor in the scrotal application, let's say 60% absorption as you mentioned, that would essentially mean that roughly only 12mg of T is actually then used by the body. Is this correct?

Click to expand...

I normally hate when people try to shut down a thoughtful analysis of something by saying I'm overthinking, but I'm going to do that here. Both you and BUD above are overthinking this. The value of better understanding the bioavailability of cream would be in its predictive power to select dosage - however, we know that bioavailability varies massively between individuals, between different application sites on the same individual, between different cream bases, between the same site on the same individual depending on whether you shaved / washed / exfoliated first, etc.

So, this endeavor is doomed before it begins. The best you're going to do is to try a certain dose, applied a certain way, get some labs done, and then perhaps you can reverse engineer how much was absorbed by comparing those results to some previous results with injections. Even then, your findings will apply to no one else, and perhaps not even to yourself at other times, given the influence of many uncontrolled variables.

ziegen said:

Finally, it seems like most of the T creams use T without an ester, but why isn't Test P used?

Click to expand...

I'm going to guess the addition of an ester makes the molecule too large to be easily absorbed.

ziegen said:

Wouldn't this be better to follow the circadian rhythm, as the half life is longer?

Click to expand...

In theory, perhaps. In practice, there is not a strong correlation between the success of TRT protocols and their similarity or dissimilarity to the natural circadian rhythm of testosterone production.

My current opinion as of this date is that you are well served to trough as low as you can stand, as frequently as you can stand it, to reduce the degree of HPTA suppression, increase neurosteroid production, give tissues a break from constant high levels of hormones, reduce adaptation/tolerance to elevated dopamine levels, etc. A shorter half-life is desirable from this perspective, as well as once daily vs twice daily application of cream.

ziegen said:

1. How exactly does half-life with cream work? With injections it's simple, you inject it and the time starts ticking, but with things like creams it's not as clear. If I understand correctly, creams, gels, etc., use Testosterone without an ester. Testosterone has a half life of 2-4 hours, however we likely have to factor in the absorption time, as I'm guessing it's not instant, but takes several hours. So you're not getting all of the T in one go, like with injections, but you're absorbing it through, let's say, 4 hours. Essentially you don't have one clear half life, but rather multiple of them, until you "fully" absorb it. This would explain why the creams work for a longer time and elevated levels of serum T are noticed at 6 and even 16 hour mark, as noted in this and another article.

Click to expand...

The skin is said to act as a reservoir for testosterone, gradually releasing it, which extends the apparent half-life.

ziegen said:

1. ...
2. I'm also interested on how the absorption itself works. In most cases, men use 10% or 20% T cream, that is 100mg/ml or 200mg/ml of T. The protocols that are most common are 1-2ml per application, applied 1-2 times a day. This means that the actual amount of T applied is between 100-400mg per day. In terms of injections this would be a massive dose, but for the cream it isn't. Obviously people aren't taking 200mg of cream per day and getting a 60% absorption. From my research it seems like the T creams only have roughly 10% of bio-available T, which would in the case of 200mg per day, mean that only 20mg of that can be used by the body. Then if we factor in the scrotal application, let's say 60% absorption as you mentioned, that would essentially mean that roughly only 12mg of T is actually then used by the body. Is this correct?

Click to expand...

The figure of 60+% absorption probably applies to relatively small doses applied to the scrotum. With such transdermal application there is likely a saturation effect, such that absorption drops off rapidly when greater amounts are applied to a limited area of skin. We can speculate that absorption may drop to 5-10% when large amounts are applied. The 5-10% absorption efficiency is instead of the 60+% figure, not as a prelude to further reduction. So 5-10% of 100-400 mg is 5-40 mg T absorbed, a range from physiological to crazy high.

ziegen said:

1. ...
2. ...
3. Finally, it seems like most of the T creams use T without an ester, but why isn't Test P used? Wouldn't this be better to follow the circadian rhythm, as the half life is longer? If the first point is correct, then in the case of Test P, the "half-life" would get "extended" maybe from 20 hours to, let's say, 30. In this case the peaks and valleys might not be as sharp, but still good enough to get the effects from following the natural rhythm. With T without an ester it seems to me that there should be quite a significant serum T drop after the 16 hour mark or so, especially if you're applying once a day.

Click to expand...

Testosterone propionate is a larger molecule, so my guess is that you would see less absorption efficiency when using it in a transdermal formulation. There's nothing to be gained over straight testosterone. The half-lives of most straight-T transdermal products are already too long to yield significant diurnal rhythms. We've discussed at length that a better way to attain a diurnal rhythm with natural amplitude is via daily injections of a blend of testosterone propionate and a longer ester, such as cypionate of enanthate. As I recall, only a particular testosterone patch yields more natural looking variation in serum testosterone.

FunkOdyssey said:

t-max 2 hours, half-life 16 hours (this info from the scrotal pharmacokinetics study with some minor extrapolation to determine half-life). This means 18 hours after application you should have half the serum testosterone levels that you had at the 2 hour peak. Serum DHT and E2 behave differently - their tmax lags behind by a couple more hours and they stay inexplicably elevated at a sort of plateau while testosterone drops.


I normally hate when people try to shut down a thoughtful analysis of something by saying I'm overthinking, but I'm going to do that here. Both you and BUD above are overthinking this. The value of better understanding the bioavailability of cream would be in its predictive power to select dosage - however, we know that bioavailability varies massively between individuals, between different application sites on the same individual, between different cream bases, between the same site on the same individual depending on whether you shaved / washed / exfoliated first, etc.

So, this endeavor is doomed before it begins. The best you're going to do is to try a certain dose, applied a certain way, get some labs done, and then perhaps you can reverse engineer how much was absorbed by comparing those results to some previous results with injections. Even then, your findings will apply to no one else, and perhaps not even to yourself at other times, given the influence of many uncontrolled variables.


I'm going to guess the addition of an ester makes the molecule too large to be easily absorbed.


In theory, perhaps. In practice, there is not a strong correlation between the success of TRT protocols and their similarity or dissimilarity to the natural circadian rhythm of testosterone production.

My current opinion as of this date is that you are well served to trough as low as you can stand, as frequently as you can stand it, to reduce the degree of HPTA suppression, increase neurosteroid production, give tissues a break from constant high levels of hormones, reduce adaptation/tolerance to elevated dopamine levels, etc. A shorter half-life is desirable from this perspective, as well as once daily vs twice daily application of cream.

Click to expand...

I see, then it means that T creams are essentially quite close to Test P, in terms of the half-life, meaning you can emulate the circadian rhythm very easily by applying in the morning, similar on how you can inject Test P in the morning. That would be the scenario I would be going for with T creams. Of course if you prefer a more constant levels of hormones, still with larger peaks and valleys, the AM+PM application of cream would take care of that.
You're right, I don't think it makes sense to over-analyze how much of the cream gets absorbed, it depends on too many factors, of the actual cream itself and the person. I just wanted to get a good base understanding of it, as with creams you're essentially applying a weeks dose of T daily, it can be a little difficult to understand if you're coming from injections. Also if you're doing some home-brews, as I'll be doing soon, then it's also useful to know, so that you don't make a 2% cream, thinking you're going to absorb anywhere near that 20mg of T.

Cataceous said:

The skin is said to act as a reservoir for testosterone, gradually releasing it, which extends the apparent half-life.


The figure of 60+% absorption probably applies to relatively small doses applied to the scrotum. With such transdermal application there is likely a saturation effect, such that absorption drops off rapidly when greater amounts are applied to a limited area of skin. We can speculate that absorption may drop to 5-10% when large amounts are applied. The 5-10% absorption efficiency is instead of the 60+% figure, not as a prelude to further reduction. So 5-10% of 100-400 mg is 5-40 mg T absorbed, a range from physiological to crazy high.


Testosterone propionate is a larger molecule, so my guess is that you would see less absorption efficiency when using it in a transdermal formulation. There's nothing to be gained over straight testosterone. The half-lives of most straight-T transdermal products are already too long to yield significant diurnal rhythms. We've discussed at length that a better way to attain a diurnal rhythm with natural amplitude is via daily injections of a blend of testosterone propionate and a longer ester, such as cypionate of enanthate. As I recall, only a particular testosterone patch yields more natural looking variation in serum testosterone.

Click to expand...

Thank you for the information. It's interesting that skin works as a reservoir. I mean it seems like the half-life gets extended enough where it's somewhat similar to Test P, then it really doesn't make sense in making a cream of Test P.

Thank you all again. As zeigen stated, I was also trying to find if there’s anyway to correlate activity, subjective effects, PK between cream and TP, simply because I find the cream to be more of a hassle than a simple daily injection of TP.
Also, as a poster above mentioned, I also believe that it is in one’s benefit, assuming they still have testicular function and responsiveness to gonadotropins, to have large variation between peak and trough for the same reason mentioned above. All theoretical, and based on n=1 subjective experience that when my central gonadotropin process is completely shut down the libido effects, especially in the morning are essentially nonexistent. This does detract some of the subjective benefits for me personally.

So all of this putzing around with low doses of TP or cream in concert with daily or Monday, Wednesday, Friday, doses of hCG and small dose of AI, Just is trying to thread the needle. I’m a difficult case without consistent long lasting subjective benefits from TRT so far.
Hcg 100u qd got my levels at total testosterone high 560s with a free testosterone 133. But my estrogen sensitive was in the mid 40s and I felt it. No ergogenic/getting fatter/poor mm build and recovery, mood, sexual function benefits.

So my next thought was to add a very small dose of testosterone cream to the scrotum, I’m talking very small like 3.125 mg And see if the increase blocks estrogen conversion and increases subjective libido.
Goal was for 700-800 tt and matched ft.
I never got to that point because of the hurricane so I started testosterone propionate 7 mg a day ,hcg 70 units Monday, Wednesday, Friday and anastrozole 0.2 mg twice a week.

This was two weeks ago. The last week I’ve experienced a nice surge in morning erections and libido, and I have no idea how this will pan out, but I’m going to stick with it for a minimum 4 to 6 weeks, test labs, keep a journal and see how this goes.

Goal is for peak 700-800s which is high physiological levels, troughs in 400-500s e2 sens in 20s and DHT upper normal. Some residual lh/fsh pulses. Shbg has always been 20s-low 30s.

Thoughts?

(Oh on the 100 hcg we only my lh was 3.something. So wasn’t shut down)

BUD987 said:

So all of this putzing around with low doses of TP or cream in concert with daily or Monday, Wednesday, Friday, doses of hCG and small dose of AI, Just is trying to thread the needle. I’m a difficult case without consistent long lasting subjective benefits from TRT so far.
Hcg 100u qd got my levels at total testosterone high 560s with a free testosterone 133. But my estrogen sensitive was in the mid 40s and I felt it. No ergogenic/getting fatter/poor mm build and recovery, mood, sexual function benefits.

So my next thought was to add a very small dose of testosterone cream to the scrotum, I’m talking very small like 3.125 mg And see if the increase blocks estrogen conversion and increases subjective libido.
Goal was for 700-800 tt and matched ft.
I never got to that point because of the hurricane so I started testosterone propionate 7 mg a day ,hcg 70 units Monday, Wednesday, Friday and anastrozole 0.2 mg twice a week.

This was two weeks ago. The last week I’ve experienced a nice surge in morning erections and libido, and I have no idea how this will pan out, but I’m going to stick with it for a minimum 4 to 6 weeks, test labs, keep a journal and see how this goes.

Goal is for peak 700-800s which is high physiological levels, troughs in 400-500s e2 sens in 20s and DHT upper normal. Some residual lh/fsh pulses. Shbg has always been 20s-low 30s.

Thoughts?

(Oh on the 100 hcg we only my lh was 3.something. So wasn’t shut down)

Click to expand...

I've been on testosterone cypionate (160-180mg/week) for a year and HCG 350iu every other day. Felt pretty good. Estrogen Ultra Sensitive serum levels were mid 70s, felt good.

Recently have been doing one pump scrotal cream in HRT base (200mg) in the morning and 75mg/week testosterone cypionate to boost my trough levels, plus the same HCG dosing. I didn't want too much DHT from cream to accelerate hair loss (I still have a full head of slightly thinning hair). I feel quite good, probably better than test cyp alone.You may want to try such a hybrid approach. A side benefit is that you can still mostly use the inexpensive testosterone oil.

Cataceous said:

The skin is said to act as a reservoir for testosterone, gradually releasing it, which extends the apparent half-life.

Click to expand...

I understand this reservoir effect when applied to e.g. the shoulders. Scrotal skin is different, also it's normally a much smaller surface area compared to shoulders.
T gel like androgel absorbs quickly into the skin. Cream preparations on the scrotum are maybe comparable to a long bath.

From the n=1 study originally posted:
" As shown in Figure 1, therapeutic levels were reached at 116 minutes and remained maintained to beyond 346 minutes. Further evidence (unpublished internal data) suggests therapeutic concentrations (>1100 ng/dL) at up to 24 hours. More research is needed to confirm these concentrations.
"