Shallow Testosterone IM versus SubQ Injections - Lab Results

[mr.craig.smith]

As many of us have learned the hard way, the reality of subcutaneous injections is often quite different than the rosy picture painted by the studies.

I wish that I had started TRT on strictly SubQ so that I wouldn't have something to compare it to lol. From a clinical perspective, I understand why it is attractive; it achieves steady state testosterone levels within therapeutic levels. It appears it just doesn't "feel" as impactful for a lot of men, and the side by side comparison shows that it also doesn't achieve the same TT or FT levels compared to IM in many cases.

I do not think subQ is "bad" or "worse". Just really shows that each person responds to injections differently, and subQ is a great way to approach injections for some people.

 

[GreenMachineX]

As many of us have learned the hard way, the reality of subcutaneous injections is often quite different than the rosy picture painted by the studies.

Truth!

 

[Fernando Almaguer]

I think with sub Q you have way less side effects like acne, hematocrit and your peak and trough levels aren't as different. Steadier levels. Ive switched to sub Q and I like it, I like it a looot

 

[Willyt]

I wish that I had started TRT on strictly SubQ so that I wouldn't have something to compare it to lol. From a clinical perspective, I understand why it is attractive; it achieves steady state testosterone levels within therapeutic levels. It appears it just doesn't "feel" as impactful for a lot of men, and the side by side comparison shows that it also doesn't achieve the same TT or FT levels compared to IM in many cases.

I do not think subQ is "bad" or "worse". Just really shows that each person responds to injections differently, and subQ is a great way to approach injections for some people.

Its also about convenience. Guys who are injecting small amounts daily often choose subq because its so easy - 5/16 into belly fat you don't even feel it. That's important is you are doing hundreds of injections every year (and thousands over a lifetime).

One thing that get little attention is fact that subq is absorbed via lymphatic system. I often wonder what impact it has on the user experience.

 

[mr.craig.smith]

Its also about convenience. Guys who are injecting small amounts daily often choose subq because its so easy - 5/16 into belly fat you don't even feel it. That's important is you are doing hundreds of injections every year (and thousands over a lifetime).

One thing that get little attention is fact that subq is absorbed via lymphatic system. I often wonder what impact it has on the user experience.

100%. I actually look forward to the small daily injections. I love the concept/idea of subQ and would prefer to not inject directly into my muscles 365 days/year. My "problem" is that I don't have a lot of fat on my abdomen so I end up basically alternating between my love handles. I don't have a ton of fat to inject into.

Have you always been on a lower dose? Has your libido improved having a lower TT trough?

My biggest complaint on TRT is that my libido has never felt super "ON", whether I'm at a higher TT. I felt the best libido wise when I was first getting on therapy again after about 6-8 weeks. I am wondering if I need to reduce my dose and then gradually work back up, or if it's just one of those things that you have a honeymoon phase in and then the body recalibrates.

I also suspect that I am primary hypogonadal because 500iu of HCG 2-3x week doesn't have really any meaningful estrogenic impact on me. I feel way better mentally taking it, but I have noticed every time I've been on therapy for the past 10 years that I have an initial response which feels good/how HCG is supposed to work, followed by feeling like I'm injecting tap water. My balls remain somewhat larger than they would without it, but I do not feel like they're doing anything else if that makes sense.

 

[FunkOdyssey]

One thing that get little attention is fact that subq is absorbed via lymphatic system. I often wonder what impact it has on the user experience.

I think this is the key to the lower testosterone levels often seen with SC injections. The testosterone is being exposed to a ton of immune cells in the lymphatic system before it is able to reach circulation. It may be eaten by macrophages (either receptor mediated uptake or phagocytosis), degraded into metabolites by enzymes expressed by immune cells, or both.

 

[madman]

Its also about convenience. Guys who are injecting small amounts daily often choose subq because its so easy - 5/16 into belly fat you don't even feel it. That's important is you are doing hundreds of injections every year (and thousands over a lifetime).

One thing that get little attention is fact that subq is absorbed via lymphatic system. I often wonder what impact it has on the user experience.

Need to rethink that one!

The main difference here between IM vs Sub-q is LAG TIME!

Key points!

* With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.


* IM (depot)--->interstitium--->lymphatics--->variable flow to systemic circulation

* Sub-q (depot)--->interstitium--->lymphatics--->steady flow to systemic circulation




* after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

* This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

* Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

*Subcutaneous vs Intramuscular Routes

The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (Tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption.

After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). However, the hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water (40). This results in some of the esterified testosterone entering the lymphatics, thus prolonging the secondary absorption phase.

The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism and is drained by the lymphatics (41). Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they likely associate with small proteins and are drained via the lymphatics into the central circulation, with the hydrolysis of these esters likely occurring in the central circulation (40). Therefore, the pharmacokinetics of testosterone esters administered via the IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration.

Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. On the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption pattern compared to IM injection.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

post #16

Figure 2

B) Schematic illustration of the absorption steps of testosterone esters after IM (left) or SC (right) injection. With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.

IM (intramuscular)

SC (subcutaneous)

post #15

NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS (2017)


CONCLUSIONS

It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two-phase mass transfer model where concentration gradients, diffusion, and partition coefficients would enable the calculation of the expected absorption. It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. The oil depot forms a continuous phase after injection but will be dispersed and encapsulated at the injection site after some days. This in turn largely influences the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

 

[mr.craig.smith]

I think this is the key to the lower testosterone levels often seen with SC injections. The testosterone is being exposed to a ton of immune cells in the lymphatic system before it is able to reach circulation. It may be eaten by macrophages (either receptor mediated uptake or phagocytosis), degraded into metabolites by enzymes expressed by immune cells, or both.

Interesting.

Need to rethink that one!

The main difference here between IM vs Sub-q is LAG TIME!

Key points!

* With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.


* IM (depot)--->interstitium--->lymphatics--->variable flow to systemic circulation

* Sub-q (depot)--->interstitium--->lymphatics--->steady flow to systemic circulation




* after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

* This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

* Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

*Subcutaneous vs Intramuscular Routes

The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (Tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption.

After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). However, the hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water (40). This results in some of the esterified testosterone entering the lymphatics, thus prolonging the secondary absorption phase.

The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism and is drained by the lymphatics (41). Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they likely associate with small proteins and are drained via the lymphatics into the central circulation, with the hydrolysis of these esters likely occurring in the central circulation (40). Therefore, the pharmacokinetics of testosterone esters administered via the IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration.

Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. On the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption pattern compared to IM injection.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

post #16

Figure 2

B) Schematic illustration of the absorption steps of testosterone esters after IM (left) or SC (right) injection. With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.

IM (intramuscular)
View attachment 51960




SC (subcutaneous)
View attachment 51961




post #15

NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS (2017)


CONCLUSIONS

It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two-phase mass transfer model where concentration gradients, diffusion, and partition coefficients would enable the calculation of the expected absorption. It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. The oil depot forms a continuous phase after injection but will be dispersed and encapsulated at the injection site after some days. This in turn largely influences the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

Hey Madman! Thank you for sharing. I'm not sure if you've had a chance to review the post I put up the other day or not, but would love your feedback if you have the time/bandwidth to review it. I can anticipate some of your suggestions after reading your replies to some other members/posts, but would be curious nonetheless if you had any thoughts.

 

[Cataceous]

I think this is the key to the lower testosterone levels often seen with SC injections. The testosterone is being exposed to a ton of immune cells in the lymphatic system before it is able to reach circulation. It may be eaten by macrophages (either receptor mediated uptake or phagocytosis), degraded into metabolites by enzymes expressed by immune cells, or both.

Any rigorous evidence for this? Until then I'll go by the studies measuring areas-under-the-curve, which do not find a difference between SC and IM. I don't discount that differing absorption rates can affect other parameters, but I remain skeptical of the disappearing-testosterone hypothesis.

 

[FunkOdyssey]

Any rigorous evidence for this?

There is not academically rigorous evidence, but there is overwhelming evidence. Literally overwhelming, in that if I summoned to this thread everyone on just this forum alone who has reported this phenomenon, you will have too many responses to manage. Let alone if I were to take the time to bring in the many TRT specialist practitioners who have observed this in their clinical practice, or users from other forums and discussion groups who have observed the same.

 

[Willyt]

Need to rethink that one!

The main difference here between IM vs Sub-q is LAG TIME!

Key points!

* With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.


* IM (depot)--->interstitium--->lymphatics--->variable flow to systemic circulation

* Sub-q (depot)--->interstitium--->lymphatics--->steady flow to systemic circulation




* after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

* This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

* Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

*Subcutaneous vs Intramuscular Routes

The IM and SC routes present a defined phase of absorption, in which the serum concentration of the drug administered progressively increases to a maximum (Cmax) and then decreases according to its elimination half-life. For testosterone esters, the time corresponding from administration to the Cmax, i.e., time of maximum concentration (Tmax), is determined by the rate at which absorption occurs, since systemic elimination of testosterone is the same regardless of the route of administration. Therefore, the formulation and the injection site influence the speed and magnitude of absorption.

After IM or SC administration of a testosterone ester, absorption occurs first by diffusion from the depot into the interstitium (Figure 2B). The physiology of the IM and SC milieu determines the patterns of absorption after administration. Molecules smaller than 1 kDa, such as testosterone, are preferentially absorbed by the blood capillaries due to the high rate of filtration and reabsorption of fluid across vascular capillaries (39). However, the hydrolysis of testosterone esters by tissue esterases is a slow process due to their high lipophilicity, with negligible spontaneous hydrolysis in water (40). This results in some of the esterified testosterone entering the lymphatics, thus prolonging the secondary absorption phase.

The interstitial fluid consists of plasma ultrafiltrate and proteins derived from tissue metabolism and is drained by the lymphatics (41). Because of their lipophilicity, testosterone esters are unlikely to have significant diffusion into the tissues; they likely associate with small proteins and are drained via the lymphatics into the central circulation, with the hydrolysis of these esters likely occurring in the central circulation (40). Therefore, the pharmacokinetics of testosterone esters administered via the IM versus SC route will vary according to the lymphatic circulation of the tissue. Lymphatic drainage is dependent on intrinsic and extrinsic pumping. Intrinsic pumping is dependent on the contraction of lymphangions (muscular unit of the lymphatics with unidirectional valves) that transport lymph by mechanisms analogous to that occurring in the cardiac chambers (42). Extrinsic pumping results from intermittent external pressure exerted by skeletal muscle contractions on the lymphatics (42). As the lymphatic drainage from SC tissue is largely dependent on intrinsic pumping, while IM lymphatic flow is also substantially influenced by extrinsic pumping during physical activity (43), these drainage patterns suggest that testosterone esters administered SC likely have more stable absorption kinetics compared to IM administration.

Similar to lymphatics, the hemorheological differences of the vascular compartments of the SC and IM tissues play a role in the pharmacokinetics of testosterone esters. As different muscle groups have variable blood flow (e.g. the blood flow to the deltoids is higher than the glutei) (44), which further varies with physical activity (45), serum on-treatment testosterone concentrations after IM injections are dependent on these characteristics. On the contrary, after SC administration, the drug is delivered to the hypodermis (adipose tissue underlying the dermis), which is not only less vascularized compared to skeletal muscles, but the flow in this region does not increase significantly with physical activity. Since the blood flow at the site of drug administration influences the pharmacokinetics of the administered drug, SC injections display a more stable vascular absorption pattern compared to IM injection.

Thread 'TRT with Subcutaneous Testosterone Injections: A Safe, Practical and Reasonable Option'

Oct 26, 2021

Abstract Context: Injections with intramuscular testosterone esters have been available for almost 8 decades and not only result in predictable serum testosterone levels but are also the most inexpensive modality. However, they are difficult to self-administer and associated with some discomfort. Recently, subcutaneous administration of testosterone esters has gained popularity, as self-administration is easier with this route. Available data, though limited, support the feasibility of this route. Here we review the pharmacokinetics and safety of subcutaneous testosterone therapy...

• madman
• subcutaneous testosterone injections
• Replies: 18
• Forum: Testosterone Basics & Questions

• 

post #16

Figure 2

B) Schematic illustration of the absorption steps of testosterone esters after IM (left) or SC (right) injection. With administration using either route, the ester exits the depot via diffusion into the interstitium from where it enters the lymphatics and subsequently reaches the circulation where it undergoes hydrolysis by intracellular esterases.

IM (intramuscular)
View attachment 51960




SC (subcutaneous)
View attachment 51961




post #15

NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS (2017)


CONCLUSIONS

It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two-phase mass transfer model where concentration gradients, diffusion, and partition coefficients would enable the calculation of the expected absorption. It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. The oil depot forms a continuous phase after injection but will be dispersed and encapsulated at the injection site after some days. This in turn largely influences the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time.

This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug.

Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.

Thanks for clarifying madman. Maybe that is why no one talks about it lol.

I was thinking about role of lymphatic system after several very strange subq experiences with Test Suspension where I felt physically sick, but did not experience that same side effect with IM. But as you know, Suspension is water-based so perhaps that is the difference.

 

[Gman86]

There is not academically rigorous evidence, but there is overwhelming evidence. Literally overwhelming, in that if I summoned to this thread everyone on just this forum alone who has reported this phenomenon, you will have too many responses to manage. Let alone if I were to take the time to bring in the many TRT specialist practitioners who have observed this in their clinical practice, or users from other forums and discussion groups who have observed the same.

This is why I always value anecdotal/ empirical experiences/ data over studies. Studies obv have their place, and are needed/ helpful, but at the end of the day, all I care about is the real world experiences that people are actually having. At the end of the day, I don’t see why anything else matters

This guy basically reiterates how I feel about the subject. Have to go to 10:20 into the vid to hear the part where he talks about how he feels empirical evidence trumps studies, and how he’d rather base his opinions on the patterns he will see while treating hundreds, if not thousands, of patients. Again, just his opinion, but I personally agree with it

But I personally have no knowledge on how testosterone gets metabolized when injecting sub Q. Just backing up what @FunkOdyssey was saying about anecdotal experiences/ evidence being important to consider, when trying to put the puzzle together on a subject

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[Fernando Almaguer]

Sub q results in more stable readings over time especially with eod dosing. I get way less acne and my total T and free T seem to be similar to IM injections. Moreover less painful injections and more sites to inject into!

 

[Willyt]

Sub q results in more stable readings over time especially with eod dosing. I get way less acne and my total T and free T seem to be similar to IM injections. Moreover less painful injections and more sites to inject into!

Where are injecting subq other then belly area?

 

[Fernando Almaguer]

Where are injecting subq other then belly area?

Pretty much belly but thats a big area, right? you can rotate without having to worry about damaging muscle tissue.