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TRT with Testosterone Undecanoate
- Thread starter Chris.N
- Start date
Testosterone replacement therapy is intended to restore normal serum testosterone levels in patients with hypogonadal disorders. Although testosterone itself is absorbed well after oral administration, it is rapidly metabolized in the intestinal wall and during its first pass through the liver, thereby inactivating approximately 98% of the amount absorbed. As a consequence, oral administration of pure, crystalline testosterone does not increase serum testosterone levels sufficiently. Such preparations are not therefore suitable for oral administration in hypogonadal disorders, as they do not result in sustained physiological serum testosterone levels. Various solutions to this problem have been developed, including injectable and transdermal routes of administration as well as sophisticated systems for oral administration that circumvent hepatic first-pass metabolism.
Testosterone undecanoate is an ester of the naturally occurring androgen, testosterone. Testosterone undecanoate (TU; 17-hydroxy-4-androsten-3-one 17-undecanoate) is an unsaturated, aliphatic, fatty acid ester of testosterone (T) in 17?-position. The active form, testosterone, is formed by cleavage of the side chain.
Nebido is an intramuscularly administered depot preparation of testosterone undecanoate and thus circumvents the first-pass effect and requires significantly less frequent injections than other established parenteral testosterone ester formulations. After the first injection, a second dose is given 6 weeks later and in the vast majority of patients, an injection every 12 weeks (with variations between 11–13 weeks) maintains plasma testosterone in the physiological range.
Following intramuscular injection of testosterone undecanoate as an oily solution, the compound is gradually released from the depot and is cleaved by serum esterases into testosterone and undecanoic acid. Testosterone, which is generated by ester cleavage from testosterone undecanoate, is metabolised and excreted the same way as endogenous testosterone. The undecanoic acid is metabolised by ß-oxidation in the same way as other aliphatic carboxylic acids.
Andriol® Testocaps® is an oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. It consists of a solution of testosterone undecanoate (TU) in an oily vehicle, contained in a soft gelatin capsule. In contrast to crystalline testosterone, TU dissolved in a lipophilic solvent significantly enhances absorption. Following oral administration, testosterone undecanoate is co-absorbed with the oleic acid from the intestine into the lymphatic system, thus circumventing the first-pass inactivation by the liver. http://www.andropause.com/about_andriol/andriol_products.pdf
Deesterification of TU to produce testosterone and 5?-reduction to produce dihydro-TU (DHTU) take place rapidly in the intestinal wall as well as in the peripheral circulation. In plasma and tissues, both testosterone undecanoate and dihydrotestosterone undecanoate are hydrolyzed to yield the natural male androgens testosterone and dihydrotestosterone.
Single administration of 80-160 mg Andriol Testocaps leads to a clinically significant increase of total plasma testosterone with peak-levels of approximately 40 nmol/l (Cmax), reached approximately 4-5 h (tmax) after administration. Plasma testosterone levels remain elevated for at least 8 hours. The bioavailability is about 7%.
As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. Andriol Testocaps must be taken with a normal meal or breakfast to ensure absorption. Many studies have shown that food can have a marked effect on drug pharmacokinetics by increasing, decreasing and/or delaying drug absorption.
A study with oral TU in men has suggested that, if taken with a meal, the TU molecules are included in chylomicrons. As a result, a significant part of the administered TU bypasses the liver and gains access to the peripheral circulation through the intestinal lymphatic system, thereby further increasing serum testosterone levels.
The effect of food on the bioavailability of oral TU was investigated in more detail. In a single-dose, randomized crossover study, the effect of a standardized meal on the pharmacokinetics of oral TU was compared with administration in a fasting state. It was found that in the fasting state hardly any TU was absorbed and oral administration of TU with food dramatically enhanced the bioavailability of TU. It was concluded that for optimal absorption, oral TU capsules must be taken with food. Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.
Schubert M, Minnemann T, Hubler D, et al. Intramuscular Testosterone Undecanoate: Pharmacokinetic Aspects of a Novel Testosterone Formulation during Long-Term Treatment of Men with Hypogonadism. J Clin Endocrinol Metab 2004;89(11):5429-34. http://jcem.endojournals.org/cgi/content/full/89/11/5429 (Intramuscular Testosterone Undecanoate: Pharmacokinetic Aspects of a Novel Testosterone Formulation during Long-Term Treatment of Men with Hypogonadism -- Schubert et al. 89 (11): 5429 -- Journal of Clinical Endocrinology & Metabolism)
In an open-label, randomized, prospective trial, we investigated pharmacokinetics and several efficacy and safety parameters of a novel, long-acting testosterone (T) undecanoate (TU) formulation in 40 hypogonadal men (serum testosterone concentrations < 5 nmol/liter). For the first 30 wk (comparative study), the patients were randomly assigned to receive either 10 x 250 mg T enanthate (TE) im every 3 wk (n = 20) or 3 x 1000 mg TU im every 6 wk (loading dose) followed by 1 x 1000 mg after an additional 9 wk (n = 20). In a follow-up study, observation continued in those patients who completed the comparative part and opted for TU treatment (8 x 1000 mg TU every 12 wk in former TU patients and 2 x 1000 mg TU every 8 wk plus 6 x 1000 mg every 12 wk in former TE patients) for an additional 20-21 months.
Here we report only the pharmacokinetic aspects of the new TU formulation for the first approximately 2.5 yr of treatment. At baseline, serum T concentrations did not significantly differ between the two study groups. In the TE group, mean trough levels of serum T were always less than 10 nmol/liter before the next injection, whereas in the TU group, mean trough levels of serum T were 14.1 {+/-} 4.5 nmol/liter after the first two doses (6-wk intervals) and 16.3 {+/-} 5.7 nmol/liter after the 9-wk interval at wk 30. The mean serum levels of dihydrotestosterone and estradiol also increased in parallel to the serum T pattern and remained within the normal range. In the follow-up study, the former TU patients (n = 20) received eight TU injections at 12-wk intervals, and the TE patients (n = 16) switched to TU and initially received two TU injections at 8-wk intervals (loading) and continued with six TU injections at 12-wk intervals (maintenance). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 {+/-} 5.2 to 16.5 {+/-} 8.0 nmol/liter) and estradiol (ranging from 98.5 {+/-} 45.2 to 80.4 {+/-} 14.4 pmol/liter).
The present study has shown that 1000 mg TU injected into male patients with hypogonadism at 12-wk intervals is well tolerated and leads to T levels within normal ranges, using four instead of 17 or more TE injections per year. An initial loading dose of either 3 x 1000 mg TU every 6 wk at the beginning of hormone substitution or 2 x 1000 mg TU every 8 wk after switching from the short-acting TE to TU were found to be a adequate dosing regimens for starting of treatment with the long-acting TU preparation.
Testosterone undecanoate is an ester of the naturally occurring androgen, testosterone. Testosterone undecanoate (TU; 17-hydroxy-4-androsten-3-one 17-undecanoate) is an unsaturated, aliphatic, fatty acid ester of testosterone (T) in 17?-position. The active form, testosterone, is formed by cleavage of the side chain.
Nebido is an intramuscularly administered depot preparation of testosterone undecanoate and thus circumvents the first-pass effect and requires significantly less frequent injections than other established parenteral testosterone ester formulations. After the first injection, a second dose is given 6 weeks later and in the vast majority of patients, an injection every 12 weeks (with variations between 11–13 weeks) maintains plasma testosterone in the physiological range.
Following intramuscular injection of testosterone undecanoate as an oily solution, the compound is gradually released from the depot and is cleaved by serum esterases into testosterone and undecanoic acid. Testosterone, which is generated by ester cleavage from testosterone undecanoate, is metabolised and excreted the same way as endogenous testosterone. The undecanoic acid is metabolised by ß-oxidation in the same way as other aliphatic carboxylic acids.
Andriol® Testocaps® is an oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. It consists of a solution of testosterone undecanoate (TU) in an oily vehicle, contained in a soft gelatin capsule. In contrast to crystalline testosterone, TU dissolved in a lipophilic solvent significantly enhances absorption. Following oral administration, testosterone undecanoate is co-absorbed with the oleic acid from the intestine into the lymphatic system, thus circumventing the first-pass inactivation by the liver. http://www.andropause.com/about_andriol/andriol_products.pdf
Deesterification of TU to produce testosterone and 5?-reduction to produce dihydro-TU (DHTU) take place rapidly in the intestinal wall as well as in the peripheral circulation. In plasma and tissues, both testosterone undecanoate and dihydrotestosterone undecanoate are hydrolyzed to yield the natural male androgens testosterone and dihydrotestosterone.
Single administration of 80-160 mg Andriol Testocaps leads to a clinically significant increase of total plasma testosterone with peak-levels of approximately 40 nmol/l (Cmax), reached approximately 4-5 h (tmax) after administration. Plasma testosterone levels remain elevated for at least 8 hours. The bioavailability is about 7%.
As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. Andriol Testocaps must be taken with a normal meal or breakfast to ensure absorption. Many studies have shown that food can have a marked effect on drug pharmacokinetics by increasing, decreasing and/or delaying drug absorption.
A study with oral TU in men has suggested that, if taken with a meal, the TU molecules are included in chylomicrons. As a result, a significant part of the administered TU bypasses the liver and gains access to the peripheral circulation through the intestinal lymphatic system, thereby further increasing serum testosterone levels.
The effect of food on the bioavailability of oral TU was investigated in more detail. In a single-dose, randomized crossover study, the effect of a standardized meal on the pharmacokinetics of oral TU was compared with administration in a fasting state. It was found that in the fasting state hardly any TU was absorbed and oral administration of TU with food dramatically enhanced the bioavailability of TU. It was concluded that for optimal absorption, oral TU capsules must be taken with food. Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.
Schubert M, Minnemann T, Hubler D, et al. Intramuscular Testosterone Undecanoate: Pharmacokinetic Aspects of a Novel Testosterone Formulation during Long-Term Treatment of Men with Hypogonadism. J Clin Endocrinol Metab 2004;89(11):5429-34. http://jcem.endojournals.org/cgi/content/full/89/11/5429 (Intramuscular Testosterone Undecanoate: Pharmacokinetic Aspects of a Novel Testosterone Formulation during Long-Term Treatment of Men with Hypogonadism -- Schubert et al. 89 (11): 5429 -- Journal of Clinical Endocrinology & Metabolism)
In an open-label, randomized, prospective trial, we investigated pharmacokinetics and several efficacy and safety parameters of a novel, long-acting testosterone (T) undecanoate (TU) formulation in 40 hypogonadal men (serum testosterone concentrations < 5 nmol/liter). For the first 30 wk (comparative study), the patients were randomly assigned to receive either 10 x 250 mg T enanthate (TE) im every 3 wk (n = 20) or 3 x 1000 mg TU im every 6 wk (loading dose) followed by 1 x 1000 mg after an additional 9 wk (n = 20). In a follow-up study, observation continued in those patients who completed the comparative part and opted for TU treatment (8 x 1000 mg TU every 12 wk in former TU patients and 2 x 1000 mg TU every 8 wk plus 6 x 1000 mg every 12 wk in former TE patients) for an additional 20-21 months.
Here we report only the pharmacokinetic aspects of the new TU formulation for the first approximately 2.5 yr of treatment. At baseline, serum T concentrations did not significantly differ between the two study groups. In the TE group, mean trough levels of serum T were always less than 10 nmol/liter before the next injection, whereas in the TU group, mean trough levels of serum T were 14.1 {+/-} 4.5 nmol/liter after the first two doses (6-wk intervals) and 16.3 {+/-} 5.7 nmol/liter after the 9-wk interval at wk 30. The mean serum levels of dihydrotestosterone and estradiol also increased in parallel to the serum T pattern and remained within the normal range. In the follow-up study, the former TU patients (n = 20) received eight TU injections at 12-wk intervals, and the TE patients (n = 16) switched to TU and initially received two TU injections at 8-wk intervals (loading) and continued with six TU injections at 12-wk intervals (maintenance). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 {+/-} 5.2 to 16.5 {+/-} 8.0 nmol/liter) and estradiol (ranging from 98.5 {+/-} 45.2 to 80.4 {+/-} 14.4 pmol/liter).
The present study has shown that 1000 mg TU injected into male patients with hypogonadism at 12-wk intervals is well tolerated and leads to T levels within normal ranges, using four instead of 17 or more TE injections per year. An initial loading dose of either 3 x 1000 mg TU every 6 wk at the beginning of hormone substitution or 2 x 1000 mg TU every 8 wk after switching from the short-acting TE to TU were found to be a adequate dosing regimens for starting of treatment with the long-acting TU preparation.
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HeadDoc
Psychologist
thanks Doc. This issue has been kicked around this board and others many times. Your clarification is the best yet.
saru
New Member
Thanks Doc. This makes the point amply clear.
"A study with oral TU in men has suggested that, if taken with a meal, the TU molecules are included in chylomicrons. As a result, a significant part of the administered TU bypasses the liver and gains access to the peripheral circulation through the intestinal lymphatic system, thereby further increasing serum testosterone levels.
The effect of food on the bioavailability of oral TU was investigated in more detail. In a single-dose, randomized crossover study, the effect of a standardized meal on the pharmacokinetics of oral TU was compared with administration in a fasting state. It was found that in the fasting state hardly any TU was absorbed and oral administration of TU with food dramatically enhanced the bioavailability of TU. It was concluded that for optimal absorption, oral TU capsules must be taken with food. Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.
It only follows that oral ingestion of shorter esters would also be picked up by the chylomicrons and bypass the hepatic first pass problem perhaps to a lessor extent. Not sure if that is useful info but see where the original misunderstanding from the article came about.
The effect of food on the bioavailability of oral TU was investigated in more detail. In a single-dose, randomized crossover study, the effect of a standardized meal on the pharmacokinetics of oral TU was compared with administration in a fasting state. It was found that in the fasting state hardly any TU was absorbed and oral administration of TU with food dramatically enhanced the bioavailability of TU. It was concluded that for optimal absorption, oral TU capsules must be taken with food. Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU.
It only follows that oral ingestion of shorter esters would also be picked up by the chylomicrons and bypass the hepatic first pass problem perhaps to a lessor extent. Not sure if that is useful info but see where the original misunderstanding from the article came about.
saru
New Member
Update: TRT with Testosterone Undeconate
Serum Total Testosterone Levels
Week 07: 731
Week 09: 613
Week 10: 572
Week 11: 492
Time to top up
PS: My T levels are usually measured at about 9:00~9:30AM (an hour after the morning peak). 8am levels must be a little bit higher.
Serum Total Testosterone Levels
Week 07: 731
Week 09: 613
Week 10: 572
Week 11: 492
Time to top up
PS: My T levels are usually measured at about 9:00~9:30AM (an hour after the morning peak). 8am levels must be a little bit higher.
mrmorris
New Member
WoW, thankyou very much, Dr. Michael Scally, M.D.
I learn a ton from you and many others on this site/forum. That was a very interesting and very informative post. Tons of info that I was not aware of. That's one of the main reasons I love it here I learn so much, That's why I am here too, and to share knowledge I already knew to other great members on this site. I look forward to being here a long time!
I just wish all the guys would get along and stop acting so childish that the only downfall. I am a very easy person to get along with. Thanks everyone including Dr Scally M.D. for all your help!
Thanks, mrmorris
I learn a ton from you and many others on this site/forum. That was a very interesting and very informative post. Tons of info that I was not aware of. That's one of the main reasons I love it here I learn so much, That's why I am here too, and to share knowledge I already knew to other great members on this site. I look forward to being here a long time!
I just wish all the guys would get along and stop acting so childish that the only downfall. I am a very easy person to get along with. Thanks everyone including Dr Scally M.D. for all your help!
Thanks, mrmorris
I sure hope this shit works out for me. I'm being injected with this every 10 weeks. A lot better than Sust 250 every 3 weeks.
I have used pellets, but went onto sustonon 250 for convieniance reasons. Am now on Readron 1000, a Australian version of Nebo. [ Bayer Schering Pharma ] I suck up the 4 ml into 4 x 100 syringes. This is a slow job. I seal up 3 and put in the fridge, using one about ever y 18 days. Total time 10 weeks before opening another vial. I love this stuff ,have good morning wood and have gained a few kg of weight, all muscle. Blood test comming up in a couple of week, and I will post here.
mac111
New Member
test shouldnt be stored in the fridge, room temp is where it should be. you'd also be better getting sterile vials and storing the stuff in them
I would have thought that storeage in preloaded syringes, with no air in it.,and with the cap over the needle, placed in new clean zipseal plastic bags, in a fridge enviroment where there is less bacteria, would be the perfect place.
With a attitude like that , I can see you do it quite regularly.
mac111
New Member
test is to be stored at room temp, not chilled.
how are you feeling on that protocol? im up for an appointment this week and nebido could be a an outcome for me.
mac111
New Member
the consultant i spoke to today told me he hasnt had any issues with anyone he has treated with Nebido, some he said have needed their injections at 10wk intervals rather than 12wks.
didnt you just discover that you've some other sort of complication and maybe bashing Nebido is inaccurate?
My endo was going to put me on it but I don't think he is anymore. I don't want to wait 4 months to find out either so I'm probably going take matters into my own hands. That other complication is probably the reason for him not putting me on it. he'd have to shoot my T levels way above normal range if he wants to fix me up.
It's true though. He's an androgen specialist who only treats men who are deficient in Testosterone and can only prescribe to men with T levels below 12 NMOI/L. Since I'm not deficient, far from actually; he keeps thinking of bullshit ways not to put me on it. He was very happy when he tested me at 4:30 pm because he thought I had a deficiency. He said to me for him to put me on testosterone, my levels would have to be lower than 12 early morning. I said "Yes but i was referred to you because I have MAIS, not low T". He then said "Let's see how the next test results look". He ordered me to have two more done but only one got through, haven't got a clue why he didn't recieve the results for the second test but again my T came high normal with high LH. And now I have to take two more tests yet again and wait till May. He is messing me around. I don't think he knows how to treat this condition at all. I would have been better off getting referred to Dr Conway, the man who diagnosed me with it. At least he specialises in AIS but his treatment protocol is outdated. He would have put me Sustanon 250 every three weeks which won't do jack. He's never treated an MAIS case seeing as it's the rarest form of AIS. I'm probably the only one in the UK diagnosed with it. There is another specialist called Leaun Hughes but I doubt I'll get referred to him now. The NHS are on a budget and I've seen three of their endo's so far and had no luck with any of them.
I have been in contact with a clinic though and had a chat with TRT doctor over there who's on TRT himself and although he'd never heard of the condition until Ie-mailed him the details; he is willing to put me on TRT if I can provide him a copy of all my blood results.
My blood record book is worth more than anything to me. If I ever lost that I'd be fucked. Which is why I treasure it. That record book is my life so I'm going to take a photocopy of every test result and store it in one of the banks safes. The book and the diagnosis letter from Dr Gerard Conway.
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