Testosterone Cypionate vs Enanthate Ester break down

[FunkOdyssey]

In this video, Peter Attia is asking Derek from MPMD whether there are different clinical outcomes between cypionate and enanthate:

Derek says people think of enanthate as a long ester, but it really sits between propionate and cypionate, where the half-life of enanthate is around 4 1/2 days and cypionate can be double that. If anyone actually experiences double the half-life from cypionate as enanthate, it seems like that could easily explain divergent outcomes.

They also talk at length about dosing frequency and Derek's position is as frequently as you can tolerate is optimal to reduce side effects that result from supraphysiological spikes. He says there are diminishing returns moving from EOD to ED but the difference between once weekly and twice weekly can be dramatic. Twice weekly is what he thinks should be minimum frequency.

 

[Cataceous]

Wasn't there someone on the forum recently with lab evidence that he was metabolizing testosterone enanthate quicker than expected? What if this is not extremely rare, and the half-lives of cypionate vs enanthate in some individuals are significantly different?

Earlier in this thread, though it's about the rate of absorption rather than metabolization. I think he's referring to testosterone enanthate in isolation. My expectation is that he would see a similarly shortened half-life with testosterone cypionate.

In this video, Peter Attia is asking Derek from MPMD whether there are different clinical outcomes between cypionate and enanthate:
...
Derek says people think of enanthate as a long ester, but it really sits between propionate and cypionate, where the half-life of enanthate is around 4 1/2 days and cypionate can be double that. If anyone actually experiences double the half-life from cypionate as enanthate, it seems like that could easily explain divergent outcomes.
...

They should have been following ExcelMale so they would not be speaking so ignorantly about Xyosted. I don't think you'll find a credible reference giving a longer (8 day) half-life for cypionate. There are one or more studies that failed to account for endogenous testosterone production. Thanks to @madman for clarifying this for me some years back. Everything else I've seen puts the half-life at about five days, including quite a few measurements by forum users.

Xyosted is interesting because it was shown to have an apparent half-life of 10 days. We believe this is because it is only testosterone enanthate in oil. Excipients such as benzyl alcohol speed up the rate of absorption.

It's true that there are many other variables affecting the rate of absorption. Nonetheless, I remain doubtful that half-life differences are primarily responsible for these reports of differences between cypionate and enanthate.

 

[Belekas]

They also talk at length about dosing frequency and Derek's position is as frequently as you can tolerate is optimal to reduce side effects that result from supraphysiological spikes. He says there are diminishing returns moving from EOD to ED but the difference between once weekly and twice weekly can be dramatic. Twice weekly is what he thinks should be minimum frequency.

Yes the difference between twice weekly and once weekly or say E5D or E6D can be dramatic af. I tried them all and the more frequent injections the worse I felt on Test-E or Sustanon250 FWIW. Pretty much as soon as I went to E5D or E6D(if I forget) from E3.5D the shit started working as expected. My BP dropped into pre TRT baseline range and also lower then ever before. No more overstimulation, feeling like a hot mess, etc. I'm just N=1 but def everyone should try and explore this as well IMO. Also I started running some supplements and doing heavy cardio on top of that so hard to stay which one or a combination of them all worked its magic. Also worth to note I'm using Pharma grade Testosterone Enanthate from India - "Testoviron Depot"

I think a lot of men got fucked up by these videos on YT where influencers or docs recommend as frequent dosing as possible, basically become a damn junky, pin every 60mins and it would be the best and most "natural" option as possible lol I think thats a complete BS and people shouldn't be afraid to explore more infrequent injection protocols FWIW.

Just my 2 cents.

 

[FunkOdyssey]

Xyosted is interesting because it was shown to have an apparent half-life of 10 days. We believe this is because it is only testosterone enanthate in oil. Excipients such as benzyl alcohol speed up the rate of absorption.

Are you accounting for the effect of SC vs IM injection with these half-life claims of 5 days for cypionate and 10 days for Xyosted? How much of Xyosted's longer half life can be attributed to SC injection?

If the difference really comes down to lack of excipients, I would expect to see similiar results with Hikma Testosterone Enanthate for example with only 0.5% chlorobutanol as preservative. That compares favorably to common formulations of cypionate and enanthate that contain relatively huge amounts of benzyl benzoate (typically 10-20% by volume). Benzyl benzoate increases drug solubility and absorption rate while chlorobutanol acts only as a preservative.

As an aside, benzyl alcohol and benzyl benzoate (which breaks down into benzyl alcohol) are associated with some nasty reactions, from anaphylaxis to something called "gasping syndrome", according to Pfizer in their Testosterone Cypionate documentation:

The preservative benzyl alcohol has been associated with serious adverse events, including the "gasping syndrome", and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys' capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity.

IMO it is too pharmacologically active a substance to include as a large proportion of testosterone formulations and I imagine it is involved in some percentage of negative reactions attributed to TRT.

 

[FunkOdyssey]

More fuel for controversy:

Testoviron Depot Dosage & Drug Information | MIMS Hong Kong

(Testoviron Depot Prescribing Info)

Contents
Testosterone enantate.
Description
Each 1ml ampoule contains 250mg Testosterone Enantate (the equivalent of about 180 mg testosterone) in oily solution.
Excipients/Inactive Ingredients: Benzyl benzoate, Castor oil for injection.
Pharmacokinetics: Following intramuscular administration of 200mg of Testosterone Enantate to 6 hypogonadal males: Peak serum testosterone levels of 1233 ± 484 ng/ml were achieved at 24 hours.
Physiological levels of testosterone (approx. 500 ng/ml) were maintained for 11 days.
Half-life in blood was 2-3 days (healthy male volunteers).

 

[Cataceous]

More fuel for controversy:
...

For even more complexity: the clinical trial for Xyosted that measured a half-life of 10 days also compared it to off-the-shelf testosterone enanthate injected IM, which had a half-life of 7.2 days. It was the West-Ward brand, and may well have used chlorobutanol as a preservative.

 

[FunkOdyssey]

For even more complexity: the clinical trial for Xyosted that measured a half-life of 10 days also compared it to off-the-shelf testosterone enanthate injected IM, which had a half-life of 7.2 days. It was the West-Ward brand, and may well have used chlorobutanol as a preservative.

So that to me seems like purely a difference of IM vs SC as chlorobutanol should not affect absorption rate.

 

[Fortunate]

Are you accounting for the effect of SC vs IM injection with these half-life claims of 5 days for cypionate and 10 days for Xyosted? How much of Xyosted's longer half life can be attributed to SC injection?

If the difference really comes down to lack of excipients, I would expect to see similiar results with Hikma Testosterone Enanthate for example with only 0.5% chlorobutanol as preservative. That compares favorably to common formulations of cypionate and enanthate that contain relatively huge amounts of benzyl benzoate (typically 10-20% by volume). Benzyl benzoate increases drug solubility and absorption rate while chlorobutanol acts only as a preservative.

As an aside, benzyl alcohol and benzyl benzoate (which breaks down into benzyl alcohol) are associated with some nasty reactions, from anaphylaxis to something called "gasping syndrome", according to Pfizer in their Testosterone Cypionate documentation:


IMO it is too pharmacologically active a substance to include as a large proportion of testosterone formulations and I imagine it is involved in some percentage of negative reactions attributed to TRT.

I think this may be true. I feel log dog shit after injecting. I have systematically tried to isolate what variable is causing it. My next test is to try to get MCT oil compounded test to compare to seed oils, but I am having a helluva time getting South Lake to fill the Rx.

Meanwhile, sadly, I am thinking @FunkOdyssey may be correct - it could very well be an excipient or preservative.

 

[FunkOdyssey]

I have a few EOD doses of Hikma testosterone enanthate under my belt and wow, this is alot better than the standard cypionate swimming in benzyl benzoate. Unfortunately, I don't know how much of the difference is the ester versus the excipients.

At this stage (about a week in), compounded cypionate at similar doses (~100 mg week) had my heart rate elevated, BP elevated, suffering from high anxiety, insomnia, swollen with water retention, severely exaggerating my LPR, and generally feeling really f*cked up. I have none of that right now, except waking slightly earlier than normal. Early days but much better experience so far. I'm actually still able to drink coffee, which I had to stop abruptly last time as I tried to counter all of those sides.

The LPR difference is really interesting and important for me as that was the major dose limiting side effect for me in the past. I did complete a course of treatment for h. pylori a few days ago, which is a big confounding variable. My suspicion was that benzyl benzoate / benzyl alcohol was relaxing the lower esophageal sphincter (it's a muscle relaxant), but that's just a wild guess.

 

[Fortunate]

I have a few EOD doses of Hikma testosterone enanthate under my belt and wow, this is alot better than the standard cypionate swimming in benzyl benzoate. Unfortunately, I don't know how much of the difference is the ester versus the excipients.

At this stage (about a week in), compounded cypionate at similar doses (~100 mg week) had my heart rate elevated, BP elevated, suffering from high anxiety, insomnia, swollen with water retention, severely exaggerating my LPR, and generally feeling really f*cked up. I have none of that right now, except waking slightly earlier than normal. Early days but much better experience so far. I'm actually still able to drink coffee, which I had to stop abruptly last time as I tried to counter all of those sides.

The LPR difference is really interesting and important for me as that was the major dose limiting side effect for me in the past. I did complete a course of treatment for h. pylori a few days ago, which is a big confounding variable. My suspicion was that benzyl benzoate / benzyl alcohol was relaxing the lower esophageal sphincter (it's a muscle relaxant), but that's just a wild guess.

Wow. This is great stuff. Please keep us informed.

I think this stuff really matters (excipients and preservatives) to some that are sensitive.

 

[Fortunate]

I have a few EOD doses of Hikma testosterone enanthate under my belt and wow, this is alot better than the standard cypionate swimming in benzyl benzoate. Unfortunately, I don't know how much of the difference is the ester versus the excipients.

At this stage (about a week in), compounded cypionate at similar doses (~100 mg week) had my heart rate elevated, BP elevated, suffering from high anxiety, insomnia, swollen with water retention, severely exaggerating my LPR, and generally feeling really f*cked up. I have none of that right now, except waking slightly earlier than normal. Early days but much better experience so far. I'm actually still able to drink coffee, which I had to stop abruptly last time as I tried to counter all of those sides.

The LPR difference is really interesting and important for me as that was the major dose limiting side effect for me in the past. I did complete a course of treatment for h. pylori a few days ago, which is a big confounding variable. My suspicion was that benzyl benzoate / benzyl alcohol was relaxing the lower esophageal sphincter (it's a muscle relaxant), but that's just a wild guess.

@FunkOdyssey, from what I understand, Hikma is the actual manufacturer, but it is sold under various brands. Which brand do you have?

 

[Fortunate]

Oh, and I forgot to follow up on my post above. I tried the MCT injections for a few days. Obviously, it's a very short time, but I noticed the same issues I did with other injections: headache and crappy feeling. So, I am inclined to say my issue is not the oil. That's not to say that some oils don't cause some problems for some people. But, I think my issue may be due to something else.

I hope @FunkOdyssey has cracked this nut for me. I'll try to find some Hikma cypionate.

 

[FunkOdyssey]

@FunkOdyssey, from what I understand, Hikma is the actual manufacturer, but it is sold under various brands. Which brand do you have?

It's sold as Hikma and I buy it through Defy's online store, then it is shipped from Empower pharmacy. Here's a pic of the box:

 

[Fortunate]

It's sold as Hikma and I buy it through Defy's online store, then it is shipped from Empower pharmacy. Here's a pic of the box:

View attachment 38826

Awesome. I want the lizard, too!

 

[FunkOdyssey]

I hope @FunkOdyssey has cracked this nut for me. I'll try to find some Hikma cypionate.

It actually has to be enanthate if you're trying to keep your testosterone formulation lean and clean. Hikma cypionate contains the usual large quantities of benzyl benzoate.

DailyMed - TESTOSTERONE CYPIONATE injection

dailymed.nlm.nih.gov

Awesome. I want the lizard, too!

Haha that's my daughter's. It makes fun sounds and lights up when you pet it, pretty cute.

 

[Gman86]

It's sold as Hikma and I buy it through Defy's online store, then it is shipped from Empower pharmacy. Here's a pic of the box:

View attachment 38826

This is the same exact test that I’m using. Get it through defy via empower as well

 

[FunkOdyssey]

This is the same exact test that I’m using. Get it through defy via empower as well

Do you also notice that it takes forever to draw up in the syringe? I've been using 31g 5/16" needles for subq injections but I might go for something larger gauge. I think one of the functions of benzyl benzoate that we're missing here is to thin out the solution and allow it to flow more easily. I'm happy to wait longer drawing my dose to feel better though.

 

[Guided_by_Voices]

I have a few EOD doses of Hikma testosterone enanthate under my belt and wow, this is alot better than the standard cypionate swimming in benzyl benzoate. Unfortunately, I don't know how much of the difference is the ester versus the excipients.

At this stage (about a week in), compounded cypionate at similar doses (~100 mg week) had my heart rate elevated, BP elevated, suffering from high anxiety, insomnia, swollen with water retention, severely exaggerating my LPR, and generally feeling really f*cked up. I have none of that right now, except waking slightly earlier than normal. Early days but much better experience so far. I'm actually still able to drink coffee, which I had to stop abruptly last time as I tried to counter all of those sides.

The LPR difference is really interesting and important for me as that was the major dose limiting side effect for me in the past. I did complete a course of treatment for h. pylori a few days ago, which is a big confounding variable. My suspicion was that benzyl benzoate / benzyl alcohol was relaxing the lower esophageal sphincter (it's a muscle relaxant), but that's just a wild guess.

Congratulations on your progress. Did you find that your resting heart rate dropped after switching to Test E? I am trying to figure out why mine is elevated.

Also, I would use a 29gauge needle for oils. I only use 31 for water-based compounds. The 29 will draw much faster, especially if you're in a warm area or slightly warm the oil.

 

[Charliebizz]

Yes the difference between twice weekly and once weekly or say E5D or E6D can be dramatic af. I tried them all and the more frequent injections the worse I felt on Test-E or Sustanon250 FWIW. Pretty much as soon as I went to E5D or E6D(if I forget) from E3.5D the shit started working as expected. My BP dropped into pre TRT baseline range and also lower then ever before. No more overstimulation, feeling like a hot mess, etc. I'm just N=1 but def everyone should try and explore this as well IMO. Also I started running some supplements and doing heavy cardio on top of that so hard to stay which one or a combination of them all worked its magic. Also worth to note I'm using Pharma grade Testosterone Enanthate from India - "Testoviron Depot"

I think a lot of men got fucked up by these videos on YT where influencers or docs recommend as frequent dosing as possible, basically become a damn junky, pin every 60mins and it would be the best and most "natural" option as possible lol I think thats a complete BS and people shouldn't be afraid to explore more infrequent injection protocols FWIW.

Just my 2 cents.

@sh1973 has always been the same way. The more frequent injections he tries. The worse he felt.

 

[FunkOdyssey]

Congratulations on your progress. Did you find that your resting heart rate dropped after switching to Test E? I am trying to figure out why mine is elevated.

So I didn't switch from cypionate to enanthate. What I'm comparing is my experience of starting trt from natural baseline, where cypionate jacked up my HR and BP and enanthate did not change it at all.

Also after this experience, I am very suspicious that the benefits @Belekas saw moving to E5D are from the change in frequency. I think a lot or even all of it might be the ester change.