Testosterone and HCG dosing schedule

[Deleted member 43589]

So you inject your HCG the same day as your test essentially. Correct?

That is an option

Nelson Vergel 's Testosterone plus HCG Protocol

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[Forty2]

I only recently added HcG to my routine, 1/2 ml twice per week. This is 10,000 iu/10ml Biostatic water. I inject 1 ml testosterone weekly. I decided on my own to get a blood test and my T came back 1500. The last test was 984. Who would believe?

That's interesting. I would not have thought that adding HCG to your TRT would increase serum testosterone much at all, since you're already suppressed.

 

[Forty2]

Absolutely the oil has an influence. I use to have a chart showing the difference but it has to do with viscosity. Castor oil has the most viscosity and is commonly used making testosterone undeconoate.

Does higher viscosity necessarily mean that it will be released slower from the depot?
MCT oil has low viscosity, but I read that it is released slowly from the depot. Is that correct?

 

[Deleted member 43589]

There is a peptide called Triptorelin that has been shown to get long time guys started again. Might look into that. It is very easy to find on the internet. Supposedly its only a 1 time injection, sub-q.

 

[madman]

Very helpful, thanks!
Does the oil the testosterone is made with influence it's half life?
Does MCT oil release quickly or slowly from the depot compared with castor oil or grapeseed oil?

The length of the side-chain ester plays a major role.

The carrier oil used can have an impact on the half-life.

Look over the Behre study I posted.

* It has been shown that different Physico-chemical properties of the oil used as a vehicle (16), as well as different injection volumes (17), may influence the kinetics of administered androgens.


Would not get too caught up on the carrier oil you are using unless you are having a bad reaction.

Again there are many other factors that affect the rate at which testosterone is released from the oily depot at the injection site.

Sub-q vs IM, the volume of injection, injection depth, site of injection, lymphatic flow, and the concentration of BOH (benzyl alcohol) is other possible factors that can affect absorption rates of the esterified hormone.




Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies (1999)
H M Behre, K Abshagen, M Oettel, D Hubler and E Nieschlag


Abstract

Objective: In the search for long-acting testosterone preparations suited for substitution therapy of hypogonadal men, testosterone undecanoate (TU) dissolved in either tea seed oil or castor oil was investigated.

Design: In study, I, 1000 mg TU in tea seed oil (125 mg/ml) were injected in equal parts into the gluteal muscles of seven hypogonadal men. In study II, 1000 mg TU in castor oil (250 mg/ml) was injected into one gluteal muscle of 14 patients.

Results: In comparison with published data on testosterone enanthate, most widely used for i.m. injections, the kinetic profiles of both TU preparations showed extended half-lives and serum levels not exceeding the upper limit of normal. The castor oil preparation had a longer half-life than TU in tea seed oil (33.9 6 4.9 vs 20.9 6 6.0 days (mean 6 S.E.M.)).

Conclusion: The longer half-life and the smaller injection volume make TU in castor oil a strong candidate for further applications in substitution therapy and in trials for male contraception.



Introduction

Testosterone has been used for substitution therapy for almost six decades. Since the number of patients suffering from hypogonadism and requiring such therapy is relatively small there has not been much drive to develop new testosterone preparations beyond subdermal implants developed in the 1940 s, enanthate and cypionate esters for i.m. injections developed in the 1950 s and oral testosterone undecanoate (TU) developed in the 1970 s. Although still in use, these preparations are not ideal because of their kinetics, resulting in either supraphysiological or fluctuating serum testosterone levels, and because of the inconvenience of frequent application (for review see reference 1). Only the possibility of new and more widespread indications stimulated a search for alternative application modalities. One result was transdermal systems well suited for long-term substitution because of almost physiological serum testosterone levels (2–4) and because of the possibility for immediate interruption of the treatment if required (e.g. when substituting hypogonadism in senescence) (5). For younger patients and for hormonal male contraception, however, long-acting testosterone preparations continue to be required.

Under the auspices of the WHO, testosterone buciclate was synthesized and tested as an i.m. injection, and in phase I studies showed an extended half-life of 29.5 days (compared with 4.5 days for conventional testosterone enanthate (TE)) (6). However, further development of this ester was hampered by the lack of an industrial partner. We, therefore, turned to TU prepared for i.m. injection in China and exhibiting an extended half-life in hypogonadal men (7). After confirmation of the long half-life in monkeys (8) we tested the Chinese preparation in hypogonadal men. Since this preparation is based on tea seed oil, uncommon in the Western pharmacopeia, TU was manufactured for clinical use in castor oil, granting a higher solubility than tea seed oil. Here we present results from a phase I study in hypogonadal men using both the Chinese and the new TU preparation.




Subjects and methods

Testosterone preparations

The TU preparation (3-oxoandrost-4-ene-17b-yl-undecanoate) used in the study I was provided and manufactured by Zhejiang Xian Ju Pharmaceutical Corp. (Zhejiang, People’s Republic of China). The steroid was dissolved in tea seed oil at a concentration of 125 mg/ml. TU used in study II was prepared by Jenapharm GmbH & Co. KG (Jena, Germany). The batch used for all injections had a concentration of 250 mg TU dissolved in 1 ml castor oil.



Study design and patients

In study, I, 1000 mg TU (2 × 4 ml on each side) were injected into each of the patient’s musculus gluteus medius on day 0 between 08.00 and 09.00 h. In study II, 1000 mg TU (4 ml volume on one injection side) was injected into one of the patient’s musculus gluteus medius at the same time of the day. The blood sampling scheme thereafter was identical in both studies. Blood samples for hormone determinations were drawn between 08.00 and 10.00 h at two control examinations (days ¹14 and ¹7), shortly before and 4 h (only study II) and 1, 2, 3, 5, and 7 days after TU injection, and then weekly up to day 56 (week 8). Blood samples for hormone determinations were separated at 800 g and stored at ¹20 8C until assayed.

Serum testosterone and estradiol were measured in all samples of both studies, while dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined only in study II.




Pharmacokinetic evaluations and statistics

For evaluation of TU pharmacokinetics and for removal of between-subject variations in basal endogenous testosterone the increments from the subject’s own baseline testosterone values were analyzed. The analysis included AUC (area under the concentration versus time curve, calculated by the trapezoidal method), Cmax (concentration maximum, calculated from the individual data), tmax (time of reaching Cmax, calculated from the individual data), and t½ b (terminal elimination half-life) (9)

Significant variations over time of any variable were evaluated by ANOVA for repeated measures. In case of a general effect over time, values at single time points were analyzed in more detail by comparison with the baseline value before injection using the Duncan multiple comparison test for repeated measures. When necessary, analysis was performed on logarithmically transformed data. P values <0.05 were considered significant. Unless otherwise stated, results are given as mean 6 S.E.M.




Discussion

Intramuscularly injected TE is the most widely used testosterone preparation when depot effects are required, e.g. for substitution of hypogonadism (1) or in trials for hormonal male contraception (10). However, after injection of the commonly administered dose of 200 or 250 mg, TE has the disadvantage that it produces supraphysiological serum testosterone levels during the days immediately following administration with a slow decline to the lower limit of normal following within 10–14 days (11). Patients dislike these swings in serum testosterone levels, which they experience as ups and downs in vigor, mood, and sexual activity. Other testosterone esters in clinical use such as testosterone cypionate or cyclohexanecarboxylate show pharmacokinetic profiles almost identical to that of TE (12, 13) so these preparations offer no therapeutic advantage.

Although the current study deals with a much higher dose of testosterone than administered in previous studies, TU does not result in supranormal serum testosterone levels, but in much-prolonged action. Extrapolating from single-dose kinetics it appears that upon repeated injections of 1000 mg, injection intervals of 6–10 weeks will be possible. The prolonged intervals and the normal serum testosterone levels throughout the injection-free period would be welcomed by the hypogonadal patient requiring substitution as well as by the eugonadal male seeking contraceptive protection.

Although different routes of administration may yield different toxicological profiles for the same drug, the lack of serious side effects from TU administered orally at doses of 80–160 mg/day over many years (14) gives reason to assume that TU applied i.m. might also be well tolerated. Indeed, no untoward side-effects have been reported from i.m. use in China (7, 15). The reason for the prolonged half-life of TU in comparison with TE is the longer aliphatic, and thus more hydrophobic, side-chain, comprising 11 instead of 7 carbon atoms. Similarly, testosterone buciclate has a prolonged duration of action, which is caused by the hydrophobic benzol ring incorporated into the side chain.

Recently, it was shown in Chinese men that i.m. injection of 1000 mg TU dissolved in tea seed oil at a concentration of 125 mg/ml has a similar pharmacokinetic profile with a t½ b of 23.7 ± 2.7 days compared with our study with the tea seed oil preparation in Caucasian men (15). The longer duration of action of TU in castor oil compared with TU in tea seed oil could be due to the properties of the oils, the different concentrations (125 vs 250 mg/ml) and injection volumes (4 vs 8 ml), as well as unilateral vs bilateral gluteal application. It is conceivable that the larger surface of the depot produced by 2 × 4 ml injections leads to a slightly faster release of testosterone ester, resulting in higher Cmax values and a slightly shorter half-life than the single 4 ml depot with more concentrated TU.

* It has been shown that different Physico-chemical properties of the oil used as a vehicle (16), as well as different injection volumes (17), may influence the kinetics of administered androgens.

In summary, i.m. TU in castor oil has a considerably longer half-life than conventional TE, producing serum levels in the normal range over 6 weeks. These properties make it an attractive candidate for substitution therapy as well as for use in male contraception.

Fundamental understanding of drug absorption from a parenteral oil depot

Abstract 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...

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4. Conclusions

This study discusses critical parameters that determine the release and absorption mechanisms of (active) substances from oil depots. It is shown that small molecules (e.g. BOH) are directly and fully absorbed, while larger, more lipophilic substances (e.g. prodrugs) exhibit an incomplete and slow absorption pattern. A lag time is seen, which is a critical parameter for absorption into the systemic circulation. This means that the absorption of compounds from a depot is significantly affected by the mass transfer in the tissue. The more lipophilic the compound, the more this plays a role. It is suggested that the concentration of the compound in the oil, the in situ surface area of the depot as well as the partition coefficient of the compound are the most important formulation parameters. The mass transfer is mainly determined by the lipophilicity of the compound, while also the lymphatic flow is suggested to be relevant for drug absorption. In oil depots, BOH is often used as an excipient. It appeared that the absorption of nandrolone is enhanced by the presence of benzyl alcohol in the first few days. Subsequently, upon BOH depletion, a change in absorption of nandrolone is seen. Injections of equivalent formulation in different muscles demonstrate that the mass transfer through these tissues is not the same. It is argued that this may be due to differences in lymphatic transport.

Spatial distribution of oil depots monitored in human muscle using MRI

Abstract Oil depots are parenteral drug formulations meant for the sustained release of lipophilic compounds. According to mass transport models, the drug-release rate from these injections is determined by the surface area of the oil depot. Until now, the size of the surface area of injected...

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Although many i.m. oil depots for sustained drug delivery have been marketed, the rate and extent of drug release are often difficult to predict. The drug-release and absorption rate from the oil solution is controlled by the drug partitioning between the oil vehicle and the tissue fluid (Kalicharan et al., 2016b). However, several other factors such as the injection site (Minto et al., 1997; Shaik et al., 2015; Soni et al., 1988), injection volume (Minto et al., 1997), the rate of bioconversion of the prodrug into the parent drug, the absorption and distribution of the oil vehicle and the extent of spreading of the depot at the injection site might affect the overall pharmacokinetic profile of the drug (Larsen et al., 2009; Weng Larsen and Larsen, 2009). Most studies focus on the pharmacokinetics of the drug rather than on the fate of the oil depot formulation (Bagchus et al., 2005; Luo et al., 1997; Morgentaler et al., 2008; Soni et al., 1988; Van Weringh et al., 1994; Wijnand et al., 1985). Thus far, only a few researchers have reported on the rate and extent of the disappearance of the injected formulation. In 2001 Larsen et al. reported a disappearance half-life of 21.4 days of an iodine-125 labeled oil depot after i.m. injection in the lower back of pigs (Larsen et al., 2001). Radioactivity was monitored by placing the scintillator probe directly on the skin surface. To date, no studies on the fate of oil depots in humans have been published yet.





4. Conclusion

The MRI method applied in this study is able to visualize the shape of an oil depot when injected into the muscle. The method enables one to estimate the surface area as well as the way the oil is disappeared from the injection site. From this, a further understanding can be obtained about the mechanism of drug absorption from oil depots. During the development of an i.m. injection, it should be taken into account that a stretched shape of the oil depot is formed in muscle. It can be argued that the oil depot is squeezed between the muscle fibers, which explains the obtained shape. As a result of this shape, the determined surface area is much larger than that of a perfect sphere that is used in mathematical models. Although the surface areas were approximately the same in all volunteers directly after injection, this was not the case in the successive days. Furthermore, the oil depot disappearance from the injection site is very variable between patients after i.m. injection. In all cases, the oil depot was disappeared from the injection site within 14 days. These factors are relevant for the absorption kinetics of active substances from oil depots and therefore contribute to the optimal therapeutic treatment in patients.

 

[Deleted member 43589]

Does higher viscosity necessarily mean that it will be released slower from the depot?
MCT oil has low viscosity, but I read that it is released slowly from the depot. Is that correct?

Seems I remember seeing that MCT has significantly less viscosity than castor oil.

Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E. Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. Eur J Endocrinol. 1999 May;140(5):414-9. doi: 10.1530/eje.0.1400414. PMID: 10229906.

Abstract​

Objective: In the search for long-acting testosterone preparations suited for substitution therapy of hypogonadal men, testosterone undecanoate (TU) dissolved in either tea seed oil or castor oil was investigated.
Design: In study I, 1000 mg TU in tea seed oil (125 mg/ml) were injected in equal parts into the gluteal muscles of seven hypogonadal men. In study II, 1000 mg TU in castor oil (250 mg/ml) were injected into one gluteal muscle of 14 patients.
Results: In comparison with published data on testosterone enanthate, most widely used for i.m. injections, the kinetic profiles of both TU preparations showed extended half-lives and serum levels not exceeding the upper limit of normal. The castor oil preparation had a longer half-life than TU in tea seed oil (33.9+/-4.9 vs 20.9+/-6.0 days (mean pm S.E.M.)).
Conclusion: The longer half-life and the smaller injection volume make TU in castor oil a strong candidate for further applications in substitution therapy and in trials for male contraception.

 

[Bremster]

That's interesting. I would not have thought that adding HCG to your TRT would increase serum testosterone much at all, since you're already suppressed.

 

[Bremster]

I have been injecting Testosterone for about 20 years, I started when I was about 70, but I am a neophyte when comes to the details of all the related meds, for example I don't know what you mean when you since I was already suppressed. I started injecting HCG recently as I said before, I got the idea by reading this forum. Not only did I get a big bounce in my T, but I noticed a significant sexual benefits as well. Also, I had some minor hip pain, it is gone, whether this a coincidence I don't know. Basically, I feel great, I just hope there is no downside.

 

[FunkOdyssey]

I have been injecting Testosterone for about 20 years, I started when I was about 70, but I am a neophyte when comes to the details of all the related meds, for example I don't know what you mean when you since I was already suppressed. I started injecting HCG recently as I said before, I got the idea by reading this forum. Not only did I get a big bounce in my T, but I noticed a significant sexual benefits as well. Also, I had some minor hip pain, it is gone, whether this a coincidence I don't know. Basically, I feel great, I just hope there is no downside.

Are you saying you are 90 years old? Wow! Do you mind sharing your protocol?

 

[Gman86]

I have been injecting Testosterone for about 20 years, I started when I was about 70, but I am a neophyte when comes to the details of all the related meds, for example I don't know what you mean when you since I was already suppressed. I started injecting HCG recently as I said before, I got the idea by reading this forum. Not only did I get a big bounce in my T, but I noticed a significant sexual benefits as well. Also, I had some minor hip pain, it is gone, whether this a coincidence I don't know. Basically, I feel great, I just hope there is no downside.

How many iu’s of HCG are u injecting per week?

 

[Bremster]

if my math is correct, by diluting 10,000iu of MCG by 10 ml of Biostatic water then 1 ml would represent a 1000 iu. 500 twice per wee.

 

[Bremster]

Are you saying you are 90 years old? Wow! Do you mind sharing your protocol?

when I was in my forties I had an agonizing reappraisa, I started working out I quit smoking, reduce drinking,got new wife (married 39 year). we both enjoy a healthy lifestyle. When I was 70 I started injecting testosterone. I haven’t really tried to optimize with other meds, pretty much just Testosterone until recently when I added HCG. I should add that I work out 6 days per week, 3 days elliptical cardio and 3 days weight, I also swim 30 minutes per day In the warmer time of the year I also have juiced vegetables for about 40 years.

 

[FunkOdyssey]

when I was in my forties I had an agonizing reappraisa, I started working out I quit smoking, reduce drinking,got new wife (married 39 year). we both enjoy a healthy lifestyle. When I was 70 I started injecting testosterone. I haven’t really tried to optimize with other meds, pretty much just Testosterone until recently when I added HCG. I should add that I work out 6 days per week, 3 days elliptical cardio and 3 days weight, I also swim 30 minutes per day In the warmer time of the year I also have juiced vegetables for about 40 years.

Hats off to you sir, you are an inspiration to us all.