Subq increased aromatiztion

[microbeast]

With the standard 10-20% benzyl benzoate formulation (benzyl benzoate is metabolized to benzyl alcohol), you have the following variables to contend with: pharmacological activity of benzyl alcohol, toxicity and inflammation caused by benzyl alcohol, and an acute spike of testosterone release.

I don't know what the exact contributions of these different factors are when it comes to producing undesirable side effects, or the contribution of cypionate vs enanthate for that matter. All I know for sure is what I reported, which is that multiple people are feeling alot better (on the same protocol otherwise) after making that switch.

Sorry but explain this to me like I'm a child. You're saying that the benzyl alcohol causes these spikes which are causing elevated absorption subcutaneously which then results in increased aromatiztion? Because all I know is I take Anastrozole I find relief which indicates it's definitely high estrogen symptoms.

 

[Kenp]

Study everyone should read: Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate - PubMed

Subq superior in every way. Higher test, lower e2 and lower HCT

 

[FunkOdyssey]

Sorry but explain this to me like I'm a child. You're saying that the benzyl alcohol causes these spikes which are causing elevated absorption subcutaneously which then results in increased aromatiztion? Because all I know is I take Anastrozole I find relief which indicates it's definitely high estrogen symptoms.

Benzyl benzoate / benzyl alcohol are messing with the normal pharmacokinetics of your testosterone ester by causing a faster release than if they were not in the formula. I think this only occurs until those excipients have been absorbed from the depot, which occurs pretty quickly in the beginning according to my understanding. So this is what creates the early spike of release, unique to that type of formulation.

Fundamental understanding of drug absorption from a parenteral oil depot - PubMed

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was...

pubmed.ncbi.nlm.nih.gov

"Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase."

 

[madman]

Study everyone should read: Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate - PubMed

Subq superior in every way. Higher test, lower e2 and lower HCT

Did you look over the thread I dropped in 2020?

Have you read the full paper from 2021 which includes any limitations in the study?

TT troughs (IM vs sub-q) were nothing to brag about.

Even then keep in mind this is not true trough (7 days post-injection) as blood was drawn 5-6 days after the last injection.


*Men were either treated with IM-TC alone, SCTE-AI alone or started with IM-TC and crossed over to SCTE-AI with at least 6 weeks of washout between the 2 treatment modalities. Dosing for IM-TC and SCTE-AI was 100 mg weekly.

*Serum values of TT (280 to 1,100 ng/dL), E2 (10 to 50 pg/mL), HCT (38.8% to 50.0%) and PSA (<2.5 ng/mL) were drawn prior to initiation of TRT and at 12-week followup. Baseline laboratory blood draws were specified to occur in the morning prior to 10:00 a.m. and 5-6 days after their last injection to observe trough TT values.

*After an average follow-up of 14.2 weeks after initiating TRT, both cohorts had significant increases in trough TT compared to their baseline levels (IM-TC:313.6 ng/dL to 536.4 ng/dL, p <0.001; SCTE-AI: 246.6ng/dL to 552.8 ng/dL, p <0.001)

*Post-therapy, the SCTE-AI cohort had significantly lower, HCT and E2, while TT and PSA levels were not significantly different between the treatment arms.




post #26 (full paper)

IM versus Sub-q T Injections: Effect on TT, hematocrit, E2, and PSA

Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate Versus Subcutaneous Testosterone Enanthate (2020) Introduction Intramuscular testosterone cypionate (IM-TC) is the conventional treatment option for hypogonadal men with baseline serum total...

www.excelmale.com

Limitations

This is the first study of the novel SCTE-AI indirect comparison to another TRT modality for the treatment of hypogonadism in men. Limitations to this study include its retrospective nature preventing randomization of patients. We also acknowledge the limitations associated with the portion of participants who had been treated with both TRT modalities, of whom all had received IM-TC prior to switching to SCTE-AI. This was performed due to constraints with our relatively small sample size. A washout period was utilized prior to SCTE-AI initiation, though a more robust study in the future would compare independent patient pools that receive only 1 TRT modality. While testosterone enanthate and testosterone cypionate are both short-acting testosterone esters, our analysis of the SCTE-AI and IM-TC compares 2 different formulations of injectable testosterone. Furthermore, our databases lacked depth in clinical information, such as body mass index, or relevant medication use, such as aromatase inhibitors, which is rarely used in tandem with TRT in our practices. We acknowledge these factors may act as unknown confounders. Lastly, as the SCTE-AI is a newer device, future studies will benefit from larger sample sizes and longer follow-ups as the SCTE-AI becomes more widely used.

 

[FunkOdyssey]

Study everyone should read: Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate - PubMed

Subq superior in every way. Higher test, lower e2 and lower HCT

Hey @Kenp , I would love to read the study but I don't have access to it. Help a brother out?

 

[Mastodont]

I'll tell you my theory: negative reactions that occur to testosterone injections in "literally minutes" are caused by excipients rather than testosterone. Or if testosterone is playing a role, it is only because benzyl benzoate causes a massive acute spike of testosterone release. Otherwise, medium and long esters of testosterone are released too slowly to do anything you could feel within minutes.

If you are having problems with anxiety on reasonable doses of compounded cypionate, you have to try pharma enanthate without benzyl benzoate and benzyl alcohol (Delatestryl and generics like Hikma T enanthate). I have multiple success stories now resolving all kinds of weird side effects, anxiety, insomnia, cognitive issues, and more by making that switch. No kidding.

It seems delatestryl has some chlorobutanol, never seen that in a t solution before, maybe it is in a non-relevant amount? In Europe there a couple of 250mg/ml enanthates in ampoules that have nothing but arrachis oil in them, been wondering how safe transferring it to an empty vial would be since there is no preservative. Then there is also the matter of carrier oils, at least arrachis or peanut oil is said to have negative effects for some. I guess this would be as easy as getting a prick test for allergies.
Btw, sustanon has 100mg/ml of benzyl alcohol in it, pretty sure that is where the PIP comes from but also pretty sure it's causing something else as well, almost as i could feel when it is leaving the system.

 

[FunkOdyssey]

It seems delatestryl has some chlorobutanol, never seen that in a t solution before, maybe it is in a non-relevant amount?

I found a great resource if you want to learn more about the effects and safety of chlorobutanol:

https://www.ema.europa.eu/en/documents/scientific-guideline/chmp-safety-working-partys-response-cmdh-questions-chlorobutanol_en.pdf

This stuff is marketed as an oral sedative drug in some parts of the world where it is sold as 150 mg tablets. With the 0.5% concentration used with testosterone enanthate, a 100 mg injection would only deliver 2.5 mg cholorobutanol. We are talking really tiny doses here.

Contrast with formulas that use benzyl benzoate and benzyl alcohol. Benzyl benzoate is typically included as 20% of total volume or 0.2 ml per 1 ml. Benzyl benzoate has a density of roughly 1 gram per ml, so your 1 ml of testosterone cypionate contains 200 mg. That means a 100 mg injection of testosterone delivers 100 mg of benzyl benzoate, plus another ~10 mg of benzyl alcohol (which benzyl benzoate metabolizes into). There are literally more excipients by weight in there than testosterone.

If you feel great on the benzyl formulas, don't worry about it. If you feel shitty after an injection, this is something to pay closer attention to.

 

[madman]

I found a great resource if you want to learn more about the effects and safety of chlorobutanol:

https://www.ema.europa.eu/en/documents/scientific-guideline/chmp-safety-working-partys-response-cmdh-questions-chlorobutanol_en.pdf

This stuff is marketed as an oral sedative drug in some parts of the world where it is sold as 150 mg tablets. With the 0.5% concentration used with testosterone enanthate, a 100 mg injection would only deliver 2.5 mg cholorobutanol. We are talking really tiny doses here.

Contrast with formulas that use benzyl benzoate and benzyl alcohol. Benzyl benzoate is typically included as 20% of total volume or 0.2 ml per 1 ml. Benzyl benzoate has a density of roughly 1 gram per ml, so your 1 ml of testosterone cypionate contains 200 mg. That means a 100 mg injection of testosterone delivers 100 mg of benzyl benzoate, plus another ~10 mg of benzyl alcohol (which benzyl benzoate metabolizes into). There are literally more excipients by weight in there than testosterone.

If you feel great on the benzyl formulas, don't worry about it. If you feel shitty after an injection, this is something to pay closer attention to.

Forgot already?

Trans scrotal testosterone cream application is a game changer

I honestly cant tell you why for sure, but I normally don’t handle my levels being that high on injections very well….it jacks me up, worsens anxiety and actually worsens “brain fog”…..the cream gave me a burst of energy but just felt “cleaner” for lack of a better word, at levels that I cannot...

www.excelmale.com

 

[FunkOdyssey]

Forgot already?

Trans scrotal testosterone cream application is a game changer

I honestly cant tell you why for sure, but I normally don’t handle my levels being that high on injections very well….it jacks me up, worsens anxiety and actually worsens “brain fog”…..the cream gave me a burst of energy but just felt “cleaner” for lack of a better word, at levels that I cannot...

www.excelmale.com

Yeah, I did. Thanks for the reminder.

 

[FunkOdyssey]

New video that argues subcutaneous injections do produce more E2 and lower T/E2 ratios than IM injections, backing this up with data from one of the Xyosted studies and a multitude of anecdotes. He also reports that switching from SC to IM injections often improves sexual function and libido in his clients on TRT:

 

[Seagal]

New video that argues subcutaneous injections do produce more E2 and lower T/E2 ratios than IM injections, backing this up with data from one of the Xyosted studies and a multitude of anecdotes. He also reports that switching from SC to IM injections often improves sexual function and libido in his clients on TRT:

Did you get the title of the paper he is talking about?

 

[FunkOdyssey]

Did you get the title of the paper he is talking about?

Found it:

Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single‐Use Autoinjector: A Phase II Study

Hypogonadism is one of the most common male endocrine problems. Although many treatments are currently available, unmet need exists for new testosterone () replacement therapies that are simple to administer and use, are safe, and mimic physiologic levels.The ...

www.ncbi.nlm.nih.gov

A summary of the main PK parameters for DHT and estradiol (E2) can be found in Table 2. Overall, the Cavg0–168 h for each metabolite was within the reference range (DHT: 4–57.5 ng/dL; E2: 10–50 pg/mL) for both doses of SC TE. The Cavg0–168 h for DHT was 30.8 ng/dL and for E2 was 25.6 pg/mL for the 50 mg SC TE group. For the 100 mg SC TE group, Cavg0–168 h for DHT was 51.9 ng/dL and for E2 was 48.3 pg/mL. The Cavg0–168h for DHT for the 200 mg IM TE group was 117.1 ng/dL. The Cavg0–168 h for E2 for the 200 mg IM TE group was comparable with that of the 100 mg SC TE group, reaching 50.0 pg/mL. The ratios of T to metabolites were similar, suggesting that the conversion rate of T to its metabolites was similar across groups.

The average DHT value across a week's time in the 200 mg IM group was roughly twice that of the 100 mg SC group which seems proportionate and makes sense.

The average E2 value in the 200 mg IM group was almost exactly the same as the 100 mg SC group! That's the shocking revelation.

 

[t_spacemonkey]

Did you get the title of the paper he is talking about?

good vid, just watched. i think i might try IM for a while. subq is working for me overall, but curious if i notice a difference. also wondering if there would be a difference between esters, like cyp/prop. on subq 25mg/d, my peak is >1500/72ng free and low is 931/30ng. e2 is 50pg/ml. I'll run my next labs at IM

 

[Mastodont]

I just recently read all there is on reddit on this topic, subq definitely seems to fail pretty often, and plenty of people also report the lower numbers on subq.

 

[HSLD]

No concerns about poking holes in muscle every other day for several decades?

Also, where are you guys injecting IM?

Delts are difficult to reach, have tried a few quad injections and they have not gone well (pain, hit a nerve or something once and my whole leg spasmed, etc).

I've always just injected subq because it's easier, not necessarily because I think it's better.

 

[FunkOdyssey]

No concerns about poking holes in muscle every other day for several decades?

Also, where are you guys injecting IM?

I don't think you can do much damage with a tiny gauge 1/2" needle. I really haven't heard about people having problems with scar tissue. Maybe with the harpoons of yesteryear?

I rotated delts, ventroglutes and quads when I was doing daily IM. With EOD, I would just stick to my favorite (delts). Ventroglutes would be my second favorite and quads in last place due to the issues you mentioned.

 

[madman]

Found it:

Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single‐Use Autoinjector: A Phase II Study

Hypogonadism is one of the most common male endocrine problems. Although many treatments are currently available, unmet need exists for new testosterone () replacement therapies that are simple to administer and use, are safe, and mimic physiologic levels.The ...

www.ncbi.nlm.nih.gov

A summary of the main PK parameters for DHT and estradiol (E2) can be found in Table 2. Overall, the Cavg0–168 h for each metabolite was within the reference range (DHT: 4–57.5 ng/dL; E2: 10–50 pg/mL) for both doses of SC TE. The Cavg0–168 h for DHT was 30.8 ng/dL and for E2 was 25.6 pg/mL for the 50 mg SC TE group. For the 100 mg SC TE group, Cavg0–168 h for DHT was 51.9 ng/dL and for E2 was 48.3 pg/mL. The Cavg0–168h for DHT for the 200 mg IM TE group was 117.1 ng/dL. The Cavg0–168 h for E2 for the 200 mg IM TE group was comparable with that of the 100 mg SC TE group, reaching 50.0 pg/mL. The ratios of T to metabolites were similar, suggesting that the conversion rate of T to its metabolites was similar across groups.

The average DHT value across a week's time in the 200 mg IM group was roughly twice that of the 100 mg SC group which seems proportionate and makes sense.

The average E2 value in the 200 mg IM group was almost exactly the same as the 100 mg SC group! That's the shocking revelation.

post #26

Subcutaneous Injection

When was testing done relative to injections? As long as you didn't have injection site leakage you should absorb the whole dose. SubQ has been shown to absorb a little more slowly than IM, but in the end you're getting all the testosterone. I injected sub q last Monday night, and tested Tuesday...

www.excelmale.com

Dr. Crisler, SQ, and studies?

These endless debates about subq versus IM baffle me. Try both protocols and see which one you like better. It's that simple. I wonder how many actually know which way they are actually injecting. Or maybe a little of both (50/50) haha.

www.excelmale.com

 

[Seagal]

Found it:

Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single‐Use Autoinjector: A Phase II Study

Hypogonadism is one of the most common male endocrine problems. Although many treatments are currently available, unmet need exists for new testosterone () replacement therapies that are simple to administer and use, are safe, and mimic physiologic levels.The ...

www.ncbi.nlm.nih.gov

A summary of the main PK parameters for DHT and estradiol (E2) can be found in Table 2. Overall, the Cavg0–168 h for each metabolite was within the reference range (DHT: 4–57.5 ng/dL; E2: 10–50 pg/mL) for both doses of SC TE. The Cavg0–168 h for DHT was 30.8 ng/dL and for E2 was 25.6 pg/mL for the 50 mg SC TE group. For the 100 mg SC TE group, Cavg0–168 h for DHT was 51.9 ng/dL and for E2 was 48.3 pg/mL. The Cavg0–168h for DHT for the 200 mg IM TE group was 117.1 ng/dL. The Cavg0–168 h for E2 for the 200 mg IM TE group was comparable with that of the 100 mg SC TE group, reaching 50.0 pg/mL. The ratios of T to metabolites were similar, suggesting that the conversion rate of T to its metabolites was similar across groups.

The average DHT value across a week's time in the 200 mg IM group was roughly twice that of the 100 mg SC group which seems proportionate and makes sense.

The average E2 value in the 200 mg IM group was almost exactly the same as the 100 mg SC group! That's the shocking revelation.

I'm sceptical about comparisons of the IM and subq arm (see limitations of study).