Trans scrotal testosterone cream application is a game changer

[Gman86]

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 tolerate on injections. Don’t know if it’s the increased DHT, the stability of the levels and shorter half life? All I know is my “thumper” didn’t want to work half the time, and even when it did it required constant stimulation to keep it going….if not for that issue I’d be on it right now….

I’m assuming the cream suppresses the HPTA less, and therefore messes with downstream hormones less, and that’s most likely where the improved cognitive function and feeling “cleaner” comes from on the cream. I could be wrong obv, but that’s my best guess currently. I think there’s a good chance the fact that cream doesn’t have an ester attached, and is truly the same bioavailable test that we produce endogenously, could have something to do with it. As well as the cream not having any of these toxic preservatives and excipients in it. Even in very small quantities, I’m sure they’re not good to be injecting on a regular basis

I theorize that the higher levels on injections causing u to feel jacked up and anxious is probably due to the lack of downstream hormones/ metabolites to balance out the higher test and DHT levels.

 

[Charliebizz]

I’m assuming the cream suppresses the HPTA less, and therefore messes with downstream hormones less, and that’s most likely where the improved cognitive function and feeling “cleaner” comes from on the cream. I could be wrong obv, but that’s my best guess currently. I think there’s a good chance the fact that cream doesn’t have an ester attached, and is truly the same bioavailable test that we produce endogenously, could have something to do with it. As well as the cream not having any of these toxic preservatives and excipients in it. Even in very small quantities, I’m sure they’re not good to be injecting on a regular basis

I theorize that the higher levels on injections causing u to feel jacked up and anxious is probably due to the lack of downstream hormones/ metabolites to balance out the higher test and DHT levels.

Not for me
on paper. My preg levels are bottomed out on cream. they weren’t on injections. And my testicle atrophy is the same on cream vs injections

 

[Gman86]

Not for me
on paper. My preg levels are bottomed out on cream. they weren’t on injections. And my testicle atrophy is the same on cream vs injections

Interesting. Is it a thing tho where when pregnenolone is being used up to convert into other downstream hormones it can show low in a blood test? Not sure if it is, jw if that’s possibly how it works. Kind of like how guys on TRT can have lower ferritin levels, because iron is being used up at a higher rate while on TRT.

does atrophied testicles automatically mean less downstream metabolite production? Does pregnenolone go through the testicles to produce metabolites such as prog, DHEA, allopregnenolone and cortisol, to name a few, or is it a completely separate conversion process that has nothing to do with what’s going on in the testicles?

 

[Charliebizz]

Interesting. Is it a thing tho where when pregnenolone is being used up to convert into other downstream hormones it can show low in a blood test? Not sure if it is, jw if that’s possibly how it works. Kind of like how guys on TRT can have lower ferritin levels, because iron is being used up at a higher rate while on TRT.

does atrophied testicles automatically mean less downstream metabolite production? Does pregnenolone go through the testicles to produce metabolites such as prog, DHEA, allopregnenolone and cortisol, to name a few, or is it a completely separate conversion process that has nothing to do with what’s going on in the testicles?

I often wondered that too. An old member I used to speak to on a regular basis lived by that same theory. That’s why blood testing for hormones is very tricky. We have no idea what’s actually going on in the cells.

 

[Fortunate]

I had a very similar experience with cream. It does feel "cleaner" and I am able to easily tolerate levels of testosterone that would destroy me with anxiety and insomnia if I reached the same level with injections.

I'm going to experiment with pharma injections that are free of benzyl benzoate and benzyl alcohol to see if that makes a difference compared to compounded injections.

@FunkOdyssey, now you’re talking my language! Where are you going to get this? I’d love to know. Only source I know of is Xyosted, which I have.

 

[TLR]

What’s the longest you’ve been on cream ?

About 3 months on two separate occasions….first time was about 2 months, then a month the second time….

 

[TLR]

I had a very similar experience with cream. It does feel "cleaner" and I am able to easily tolerate levels of testosterone that would destroy me with anxiety and insomnia if I reached the same level with injections.

I'm going to experiment with pharma injections that are free of benzyl benzoate and benzyl alcohol to see if that makes a difference compared to compounded injections.

Did you also have the erectile difficulties while on it??

 

[FunkOdyssey]

Did you also have the erectile difficulties while on it??

No, I had better erectile function with cream actually.

 

[FunkOdyssey]

@FunkOdyssey, now you’re talking my language! Where are you going to get this? I’d love to know. Only source I know of is Xyosted, which I have.

It's Hikma Testosterone Enanthate, which only has sesame oil and 0.5% chlorobutanol. That is the lowest possible concentration of a preservative I have seen in a multi-use vial. Chlorobutanol is given as a sedative drug in large doses like 150+ mg orally and seems pretty harmless in the tiny doses you would inject.

 

[Gman86]

It's Hikma Testosterone Enanthate, which only has sesame oil and 0.5% chlorobutanol. That is the lowest possible concentration of a preservative I have seen in a multi-use vial. Chlorobutanol is given as a sedative drug in large doses like 150+ mg orally and seems pretty harmless in the tiny doses you would inject.

Im also using Hikma test enanthate

 

[Fortunate]

It's Hikma Testosterone Enanthate, which only has sesame oil and 0.5% chlorobutanol. That is the lowest possible concentration of a preservative I have seen in a multi-use vial. Chlorobutanol is given as a sedative drug in large doses like 150+ mg orally and seems pretty harmless in the tiny doses you would inject.

So, do you just have your provider call prescription to a pharmacy that sells it? How do you get your hands on it?

 

[FunkOdyssey]

So, do you just have your provider call prescription to a pharmacy that sells it? How do you get your hands on it?

Defy sells it via Empower pharmacy. It costs a bit more than their compounded T but not too much.

I asked Empower if they were able to compound T using the same formula (tiny bit of chlorobutanol instead of alot of benzyl benzoate/benzyl alcohol) and they said no, they cannot produce anything custom that deviates from their standard recipes.

 

[Fortunate]

Defy sells it via Empower pharmacy. It costs a bit more than their compounded T but not too much.

I asked Empower if they were able to compound T using the same formula (tiny bit of chlorobutanol instead of alot of benzyl benzoate/benzyl alcohol) and they said no, they cannot produce anything custom that deviates from their standard recipes.

At some point, you may also consider getting a Xyosted pen and trying that.

 

[madman]

It's Hikma Testosterone Enanthate, which only has sesame oil and 0.5% chlorobutanol. That is the lowest possible concentration of a preservative I have seen in a multi-use vial. Chlorobutanol is given as a sedative drug in large doses like 150+ mg orally and seems pretty harmless in the tiny doses you would inject.

Hikma TE is the generic version of the brand named Delatestryl.

Both formulations use sesame oil as the carrier and 0.5% chlorobutanol as a preservative.

Your only option for preservative-free TE would be Xyosted.

The main drawback when using Xyosted is you are stuck with injecting a fixed dose of TE 50 mg, 75 mg, or 100 mg, and of course, the cost if it's not covered by insurance.

There are no preservatives added as it is a single-dose syringe.

*XYOSTED (testosterone enanthate) injection is a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution supplied in a single-dose syringe assembled in a pressure-assisted autoinjector for subcutaneous administration.




Delatestryl®

DOSAGE FORMS, COMPOSITION AND PACKAGING

DELATESTRYL is a sterile, oily testosterone enanthate solution for intramuscular use. It is available in a potency of 200 mg per mL formulated in sesame oil with 0.5% chlorobutanol as a preservative. It is available in glass vials containing 5 mL, sealed with latex-free stoppers.




XYOSTED®

XYOSTED (testosterone enanthate) injection is a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution supplied in a single-dose syringe assembled in a pressure-assisted autoinjector for subcutaneous administration. Each XYOSTED autoinjector contains 50 mg, 75 mg, or 100 mg of testosterone enanthate dissolved in 0.5 mL of sesame oil providing three product strengths of 50 mg/0.5 mL, 75 mg/0.5 mL, and 100mg/0.5 mL









SWP response to CMDh questions on chlorobutanol

1. CMDh questions to SWP

1. Can the SWP confirm that the levels of chlorobutanol generally used in medicinal products are safe from a toxicological point of view?

2. Is it feasible to determine acceptable intake levels of chlorobutanol?




2. SWP response to CDMh questions

2.1. Assessment of data

Chlorobutanol (synonyms: trichloro-2-methyl-2-propanol, chlorbutol, chloreton, chloretone, chlortran)is used as a preservative due to its antibacterial and antifungal properties. As excipient it is used up toconcentrations of 0.5% in injectables (e.g. methadone, epinephrine, oxytocin, morphine, desmopressin, thiamine), ophthalmic (e.g. pilocarpine, epinephrine, phospholine iodide), otic (e.g.Cresylate, Cerumenex) and cosmetic products.

Due to its sedative and hypnotic effects, it is also used as the active ingredient in oral sedatives marketed outside the EU (e.g. Seducaps: 150 mg chlorobutanol/300 mg salicylamide). In addition, topical anesthetics may also contain chlorobutanol.

Results of a Japanese OECD TG 422 Combined Repeat-dose toxicity study with the production/developmental toxicity screening test which had not been taken into account in previous assessment procedures, were received and evaluated for deriving a PDE of chlorobutanol.




2.1.1. Human data

Human data from controlled studies on pharmacologic/toxicologic effects are not available in the public domain. However, there are several published case reports on the use of chlorobutanol either as medication, as a preservative in medicinal preparations, or from poisonings. The reported pharmacological and toxicological effects include CNS effects such as somnolence, drowsiness, slow speech, dysarthria, sluggish reflexes, disorientation, coma, generalized hypertonia, hyperreflexia, hypersalivation, and trismus. In addition, chlorobutanol has been demonstrated to induce hypersensitivity reactions, and low blood pressure and may have the potential to prolong the QT interval (Valentour et al., 1975; Borody et al., 1979; Dux et al., 1981; Itabashi et al., 1982; Hofmann et al.,1986; Vaillancourt et al., 1992; Bowler et al., 1986; Nordt et al., 1996; Brun et al., 2010; Woosley et al., 2019).

Preclinical data with regard to neurotoxicity could not be identified. However, preclinical data on cardiotoxicity are available (see 2.1.3).

Limited data on human pharmacokinetics are available from one published study (Tung et al., 1982). In this study, 600 mg chlorobutanol was orally administered to four healthy male subjects (aged 20–30) on two occasions, where the second dose was administered at least 2 months after the first dose. Chlorobutanol displayed a high volume of distribution and low plasma clearance with a long half-life of 10 days. Peak plasma concentrations of ~4–5 µg/mL were reached 15–60 min after administration.

A plasma half-life of 13.2 days has been reported in a case of high doses of chlorobutanol as a sedative (Seducaps, chlorobutanol 150 mg in combination with salicylamide 300 mg). Repeated ingestion of large amounts (6–10 capsules per day corresponding to 900–1500 mg/d chlorobutanol) were leading to plasma levels of ~100 µg/mL (Borody et al., 1979).

Overall, these studies suggest that chlorobutanol might accumulate in humans when administered repeatedly.

The oral lethal human dose of chlorobutanol is estimated to be 50–500 mg/kg (Nordt et al., 1996).




2.1.2. Antiplatelet effect

Some in vitro studies with human plasma indicated that chlorobutanol inhibits human platelet aggregation and release. Chlorobutanol produced a potent concentration-dependent inhibition of platelet aggregation and release of platelet-rich plasma. It exhibited a significant inhibitory activity towards aggregation inducers in a concentration- and time-dependent manner (Chen SL et al., 1990). However, it was concluded that the antiplatelet effect of chlorobutanol was most likely due to its generalized adverse effect on the arachidonic acid pathway. In addition, its action was found to be readily reversible.


Conclusion

Chlorobutanol was considered most likely not to have an unspecific toxic effect on platelets in vivo (Chen SL et al., 1990).




2.1.3. Cardiotoxicity

A published study (Hermsmeyer K et al., 1976) reported that chlorobutanol exerts a direct myocardial membrane excitation action and depressed contractility in vitro on toad, frog, or rat myocardium. Chlorobutanol (500 μg/ml ~2.8 mM) caused a 30% decrease in contraction amplitude and a 20%increase in action-potential duration. These effects produced by chlorobutanol were rapid in onset, appearing within 15 seconds and reaching a steady state within 5–10 min. The amplitude of the isometric contraction remained depressed during continued perfusion with chlorobutanol solution and returned to the control level within 10 mins after chlorobutanol washout. The mechanism by which chlorobutanol exerted its negative inotropic effect involved conduction disruption and desynchronization of contraction. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips.

Mechanistically, chlorobutanol inhibits hERG currents at therapeutically relevant millimolar concentrations (the IC50 values are 4.4–7.4 mM (Kornick et al., 2003; Friemel and Zünkler 2010). For comparison, plasma concentrations of about 0.5 mM (~88 µg/mL) chlorobutanol were reported in a patient receiving IV morphine preserved with 0.5% (about 30 mM) chlorobutanol (DeChristoforo et al.,1983). The ratio of the IC50 value for the block of hERG currents (4.4–7.4 mM) to the plasma concentration of chlorobutanol is below the margin of 30 and might indicate a torsadogenic potential of chlorobutanol according to the criteria developed by Redfern et al. (2003). However, the torsadogenicpotential induced by block of hERG currents can be counterbalanced by effects on other types of cardiac ion channels (e.g. Na+ and L-type Ca2+ channels), and further in vitro and in vivo electrophysiological studies are required to test the torsadogenic potential of chlorobutanol.

In addition, interactions between chlorobutanol and a hERG channel blocker binding inside the central cavity (terfenadine) of the channel produce synergistic inhibitory effects on hERG currents (Friemel andZünkler, 2010). Depending on both the site and the speed of injection, it is likely that the concentration of chlorobutanol in the heart may approach the level (2.5 mM ~439 µg/mL) at which synergistic inhibitory effects on hERG currents with simultaneously administered pore blockers of the hERG channel can be observed.

A recent review addresses the question, of which IV drug formulations on the US market contain chlorobutanol and if they are associated with Torsade de Pointes (TdP) arrhythmias (Woosley et al.,2019). Nine drugs (methadone, epinephrine, papaverine, oxytocin, vasopressin, testosterone, estradiol, isoniazid, and desmopressin) containing 2.5 mg/mL or 5.0 mg/mL chlorobutanol were identified. For all nine drugs QT prolongation or TdP was reported in the FDA’s Adverse Event Reporting System (FAERS) and for five the same was reported in PubMed. Two of the nine drugs had positive signals (by disproportionality analysis) for TdP in FAERS (EB05 2.88 and 23.81, respectively), and four were reported in published articles as the suspect drugs in cases of TdP. Exposure at the recommended dose ranged from 2–500 mg/d chlorobutanol (Table 1).


Note for testosterone and estradiol - QT prolongation or TdP

Conclusion

Chlorobutanol is a hERG blocker, which acts synergistically with simultaneously administered poreblockers. US Pharmacovigilance and published data indicate a risk of QT prolongation or TdP arrhythmias for several IV applied drugs preserved with chlorobutanol (dose range 2–500 mg/chlorobutanol, 0.04–10 mg/kg bw/d respectively). As preclinical in vivo data and clinical QT studies with chlorobutanol are lacking, no firm conclusion on cardiac safety can be drawn. However, based on the available data a cardiotoxic risk of chlorobutanol-containing IV formulations especially when given in conjunction with hERG blockers such as methadone cannot be excluded.

 

[Jerajera]

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”….

I have the same experience you do on injections. I've just started 12mg/day Test C. How do you feel on 70-80mg/week? Do you do daily injections? subQ/IM?

I'm hesitating between IM and subQ but I think i'll give subQ a try. When I started taking Test I started with subQ and seem to remember my T:E2 ratio being higher.

 

[TLR]

I have the same experience you do on injections. I've just started 12mg/day Test C. How do you feel on 70-80mg/week? Do you do daily injections? subQ/IM?

I'm hesitating between IM and subQ but I think i'll give subQ a try. When I started taking Test I started with subQ and seem to remember my T:E2 ratio being higher.

I inject shallow IM in the delt or quad on Sunday and Wednesday….35-40 mg each injection. I started at 200 mg a week and have been on 150, 120, 100 and 60 as my other doses, along with the mentioned trial of cream….I wasted several years messing with higher doses / AIs, etc. before finally lowering my dose. If I’m on injections this is where I feel best at….

 

[Charliebizz]

I inject shallow IM in the delt or quad on Sunday and Wednesday….35-40 mg each injection. I started at 200 mg a week and have been on 150, 120, 100 and 60 as my other doses, along with the mentioned trial of cream….I wasted several years messing with higher doses / AIs, etc. before finally lowering my dose. If I’m on injections this is where I feel best at….

What are you levels on th lower dose. I think calling doses “high” or “low” is kind of what muddys the waters. Most would call 5 clicks of atrevis base cream a super high dose. But my peak is only 800.

That’s what held me back so long from feeling well. I was more focused on the dose then my actual numbers. And I’ll take it one step further. I think the numbers can be irrelevant because we don’t actually know what’s going on in the cells

 

[TLR]

What are you levels on th lower dose. I think calling doses “high” or “low” is kind of what muddys the waters. Most would call 5 clicks of atrevis base cream a super high dose. But my peak is only 800.

That’s what held me back so long from feeling well. I was more focused on the dose then my actual numbers. And I’ll take it one step further. I think the numbers can be irrelevant because we don’t actually know what’s going on in the cells

No doubt “dose” is relative to each individual….I hardly check FT anymore, but TT is usually in the 700-800 Range, E2 high 20s to low 30s….on injections if I go any higher than that it aggravates pre existing anxiety and results in PVCs and just a “wired but tired” feeling….the interesting thing was being on the cream where my levels were at 1200 I didn’t feel that way, but my E2 was at like 58 and I just had the erection issues. I don’t know for “sure” if it was the E2, but when I was on higher doses of injectables and my E2 climbed I had the same thing happen. I dropped AIs years ago after doing the yo-yo thing and crashing a couple of times (apparently all I have to do is lick anastrozole and it drops me 20 points)….

 

[Charliebizz]

No doubt “dose” is relative to each individual….I hardly check FT anymore, but TT is usually in the 700-800 Range, E2 high 20s to low 30s….on injections if I go any higher than that it aggravates pre existing anxiety and results in PVCs and just a “wired but tired” feeling….the interesting thing was being on the cream where my levels were at 1200 I didn’t feel that way, but my E2 was at like 58 and I just had the erection issues. I don’t know for “sure” if it was the E2, but when I was on higher doses of injectables and my E2 climbed I had the same thing happen. I dropped AIs years ago after doing the yo-yo thing and crashing a couple of times (apparently all I have to do is lick anastrozole and it drops me 20 points)….

Is it possible that those levels (on cream) are just a tad bit high ? Leading to erection issues ?

 

[Jerajera]

I inject shallow IM in the delt or quad on Sunday and Wednesday….35-40 mg each injection. I started at 200 mg a week and have been on 150, 120, 100 and 60 as my other doses, along with the mentioned trial of cream….I wasted several years messing with higher doses / AIs, etc. before finally lowering my dose. If I’m on injections this is where I feel best at….

Thanks for replying. I think I'm slowly reaching the same conclusion about lower dosages.
I'm going to give 12mg/day subQ a try and see what happens.