Testosterone undecanoate and trt

jboldman

New Member
Since there seems to be some interest in this....


jb


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J Clin Endocrinol Metab. 2004 Nov;89(11):5429-34. Related Articles, Links


Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism.

Schubert M, Minnemann T, Hubler D, Rouskova D, Christoph A, Oettel M, Ernst M, Mellinger U, Krone W, Jockenhovel F.

Klinik II und Poliklinik fur Innere Medizin der Universitat zu Koln, Germany.

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.



Age Ageing. 2005 Mar;34(2):125-30. Epub 2004 Dec 13. Related Articles, Links


Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status.

Haren M, Chapman I, Coates P, Morley J, Wittert G.

University of Adelaide, Department of Medicine, Adelaide, South Australia, Australia.

BACKGROUND: relative androgen deficiency in ageing males is assumed to have adverse health effects. This study assessed the effect of 12 months' standard dose, oral testosterone, on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men. METHODS: testosterone undecanoate (TU, 80 mg bid) or placebo was administered for one year to 76 healthy men, 60 years or older, with a free testosterone index (FTI) of 0.3-0.5 and significant symptoms on a questionnaire designed to evaluate androgen deficiency (ADAM). The ADAM was completed at baseline, 6 and 12 months. Hormone and safety data were collected at baseline, 1, 3, 6 and 12 months. RESULTS: after 12 months, plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group (P = 0.01). FTI and calculated bioavailable testosterone (cBT) were greater in the testosterone group as compared with the placebo group (P = 0.021 and 0.025, respectively). There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU. However, there were trends toward improvements in sadness/grumpiness (P = 0.063), reduced erection strength (P = 0.059) and decreased work performance symptoms (P = 0.077), particularly in men with baseline cBT levels below 3.1 nmol/l. CONCLUSIONS: this study concludes that 80 mg bid oral TU does not improve overall ADAM questionnaire scores in older men with low-normal gonadal status. Oral TU may preserve mood and erectile function, as assessed by this questionnaire, particularly in men with the lowest testosterone levels.

Drugs R D. 2004;5(6):368-9. Related Articles, Links


Testosterone Undecanoate-Schering AG.

[No authors listed]

Schering AG is developing a formulation of testosterone undecanoate [Nebido] for the treatment of testosterone deficiency or hypogonadism. This deficiency can lead to decreased muscle mass, impaired muscle function, osteoporosis, reduced sexual function and mental degeneration.Schering claims that its new formulation provides superior control of blood levels of the drug and permits a longer period of application. Nebido requires only four injections per year, and represents a major improvement for men with testosterone deficiency.Schering AG received approval of its testosterone undecanoate formulation in its first European country, Finland, in November 2003 for the treatment of hypogonadism in men. In July 2004, Schering's testosterone undecanoate formulation completed approval of the European mutual recognition procedure. This approval clears the way for marketing the product (as Nebido) in the large pharmaceutical markets like Germany, France and the UK. The initial phase of the product launch will occur in Finland in October 2004, and in Germany in November 2004. Other European countries will follow in 2005, and following receipt of approval, it will be introduced in the first Latin American and Asian countries.In its 2002 Annual Report, Schering predicted that testosterone undecanoate has the potential to reach peak sales of euro 100 million, 3 years after launch-launch in Europe was at the time anticipated in 2004.
 
You would think this would be the perfect test for hrt particularly when combined with hcg on the lower side of the curve. It would reduce the larger swings in test blood levels and eliminate the need for weekly shots. Just for info purposes here is what your blood levels look like after a 100mg shot of test. Note where on the graph they are after 7 days.

jb

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The points made in the first provided study have nothing to do with a comparison to the innappropriately administered TC TRT (q 3 week injections).

The TU listed in the second study is the oral prep known as Andriol. It is not currently FDA-approved in the US, to my knowledge, but I hear another oral TU product is on the way.

I met with Mr Gord Tonnelly in Canada in 2003. He is considered the world's foremost authority on the oral TU preparation. At that time, even he had largely abandoned its use, but told me he sometimes had to due to reimbursement issues with the Canadian socialized medicine system.

Issues with Andriol include inconsistency in serum levels, not just patient-to-patient, but literally dose-to-dose. Pharmacies do not like refrigerating it, too. I believe it must be dosed several times per day, so patient complience is an issue as well.

He has told me that if you take Andriol with a 20 gram fat load (!) you can dramatically improve its performance. That is no doubt due to its lymphatic absorption process.

Injectable TU would require a HUGE injection, volume wise, each time, as TRT patients need roughly 55mg of T actually into their systems (once the ester is separated from the T molecule, and half-life is considered) per week if giving injections at such long intervals. What IS the volume of a 1000mg TU dose?

But the real problem with IM TU is one of logistics. I can tell you that my new patients are chomping at the bit to get their T levels tuned up. If one is dead-set on administering appropriate TRT, you must wait several half-lives of the medication for serum hormone levels to stabilize. I do not think they want to wait that long. One must also then wait a similar amount of time to re-stabilize following dosing changes.

Testicular atrophy would be much worse then, as I do not add my HCG Protocol in until T is properly tuned up first.

Current thinking is that we do not provide TRT to gentlemen who are newly discovered to have prostate cancer. Therefore the existence of a testosterone preparation with such a long half-life in my patient's body, should that occur, is not a pleasant thought.

Filling in for the lower serum T levels at the end of the "cycle" with HCG seems counterproductive if one is using this prep to avoid more regular injections. You then are required to every day, or at least every other day, SC injections of HCG, for weeks.

The protocols I have developed allow me to tightly control serum androgen levels, while stabilizing same, maintain testicular size, and also to support the other hormonal pathways which begin with CHOL. For me, TC is unparalleled for IM TRT.
 
so some of the same problems with tu are similar to those with the testosterone pellets. The effective minimum dose is too difficult to predict clinically. On a similar topic, extended release psychotropics can be tricky to stabilize. For instance, concerta, an extended release stimulant, should really be initiated only after the starting dose is estimated based up patient response to multiple dosing of ritalin.
 
First, I want to officially welcome HeadDoc. He is known as a true gentleman of the Board community.

Your analogy to testosterone pellets is a good one, indeed.
 
Thanks Swale. I actually joined Meso @ the same time as you. Just kept busy elsewhere. As I'm now officially in the "young/old" category I'm payng more attention to this notion of minimal effective dose of strong medicines. My own review of the WHI study on female hrt sensitized me to this big time. If TU does get FDA approved, you will, of course, have to figure out the inherent problems of stability and managing side effects.
 
i dropped my gum in my milk..dam!

What IS the volume of a 1000mg TU dose? i think i seen somewhere ..it was 4ml injection... i could be wrong though..........
 
What if you were to take the testosterone undecanoate injections along with the cypionate or enanthate injections? Would your blood levels be stabilzed a little better in the long run, like if doctors put you on the cypionate until the undecanoate kicked in a month later, then continued with the undecanoate after that, or maybe continued both and used less frequent cypionate injections. Would that make any sense?

Also Ive heard about Andriol (oral version of testosterone undecanoate) and heard it sucks in price and effective dose so I dont care for that one at all.

Does anyone here have a graph of a testosterone undecanoate injection, how long is the half life and how much testosterone is in a 200mg shot, must be like 100mg. or something right?
 
ARNOLD73 said:
Also Ive heard about Andriol (oral version of testosterone undecanoate) and heard it sucks in price and effective dose so I dont care for that one at all.
True. I think it needs to be taken at least 4 times a day. That's pretty expensive stuff. That's why Androgel is so much more expensive than Test Cyp. Only 10% of the Androgel makes it through the skin - that and the daily application makes it quite costly.
 
HeadDoc--No, I just won't be working with it. Who needs the hassles? And who needs 4mL injections?

GG--Testosterone gel is not expensive to make.
 
it maybe be a 4ml injection but if u only have to do them every few months it would be a welcomed thing.......... androgel is a ripoff..... there is nothing in it that would boost the price of it that much over test cyp....... maybe those pretty foil packs cost alot?
 
I think it is the profit that costs alot. Compounding pharmacies are much cheaper.
 
Swale, if Testosterone Undecanoate was made for injection in the U.S. would you put your patients on it. I mean wouldnt it be easier to just do one injection a month for instance of 3ml of 600mg.. I mean you think it would be a good alternative for guys who dont really like to inject once a week (or lets say cant inject once a week due to traveling on the road alot as a truck driver and would not want to take medicine on the road). What do you think?
 
i agree that it would require tuning up but as was suggested that could be accomplished quicker if you frontloaded. Depending on how low you are willing to let test get before adding more you could adjust the frequency of the shots by a few days. Don't you now have your patients administer hcg twice a week? In the TU scenario i would doubt that it would be needed for more than one week during the shot cycle if at all if you adjusted the shot frequency.

Good point about the prostate issues, perhaps for older recipients, the shorter esters would be better.

I don't think the oral TU would be a candidate in any case for many of the reasons already pointed out.

Bottom line is it probably would require a lot of doc patient interaction to get a good working protocol although you might be able to contact some of the EU doc's using it and shorten the process.

jb
 
I guess I just feel that I have developed what is nearly the perfect TRT protocol already. It does everything we need it to. IOW, it ain't broke...

I do not want my guys injecting several cc's at a time. I fail to see how that is better than a once weekly .5cc.

Frontloading would require a huge amount of oil to be injected at once. I am more comfortable with the body's ability to handle small amounts of the foreign substances which come with the testosterone, but not that much all at once. I wonder what deleterious effects we may discover one day from these substances.

As I was fielding questions from the physicians in the audience at the end of one of my lectures at the A4M International Congress in Chicago last August, one of the docs offered some striking thoughts regarding the possible ill effects of injecting the oils and BA, long-term, in TRT. I could only agree with him.

Who wants to take a full year to get themselves tuned up?

On the contrary, I think TU would require a physician to NOT want to go through all it would take to masterfully administer it for TRT; rather, someone who just wants to write a script, and send the patient on their way. IMPO, if a doctor REALLY thinks it through, he/she would not use this particular ester for TRT.
 
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