Low T, Cryptorchidism, i want optimal

[MickD84]

I am 41 years old. As a young child i suffered testicular damage which actually displaced one of my testicles. I had to have surgery to have it moved back into the scrotum. I'll bullet point this to save wasted words...

- Puberty, despite being skinny and playing sports, got developed-boobs.
- At 37, changed my life completely. Diet, hard training in the gym, constant exersize. Still had the man-boobs. Made me do some research. Got bloods done.

Testosterone - 9.6nmol
SHBG - 23 nmol
Calculated Free Test - 234

- Researched hypogonadism and its causes, including testicular damage. Found out my T was extremely low. Got on Testosterone from an Endocrinologist for about 18 months.

My testosterone is now 14.0nmol. I understand that this falls on the low end of the category as normal levels for my age group (41). My endo will not give me Testosterone anymore. I am extremely active, lift heavy 5 times a week, work in active outdoor employment and in my free time am surfing/playing sport etc. I eat VERY healthy. I consider this to still be low for me, as i am not your average 41 year old and i dont think i should be compared on a list of 41 year olds, who mostly are fat and lazy. I want to be optimal.

So my question is.... how do i go about getting Testosterone another way if my endocrinologist (Who is absurdly fat and unhealthy himself) wont give it to me? Is there online endo's who are more modern and dont use a flat scale for everyone?

Thank you for your time.

 

[Systemlord]

My endo will not give me Testosterone anymore.

You need to get your FT to the top end of the ranges or higher!

You may need to seek private care through a TRT clinic to get proper treatment.

The calculated FT can be off by as much as 40%!

So my question is.... how do i go about getting Testosterone another way if my endocrinologist (Who is absurdly fat and unhealthy himself) wont give it to me?

Balance My Hormones in Dorset. They offer TRT across Europe.

 

[madman]

I am 41 years old. As a young child i suffered testicular damage which actually displaced one of my testicles. I had to have surgery to have it moved back into the scrotum. I'll bullet point this to save wasted words...

- Puberty, despite being skinny and playing sports, got developed-boobs.
- At 37, changed my life completely. Diet, hard training in the gym, constant exersize. Still had the man-boobs. Made me do some research. Got bloods done.

Testosterone - 9.6nmol
SHBG - 23 nmol
Calculated Free Test - 234

- Researched hypogonadism and its causes, including testicular damage. Found out my T was extremely low. Got on Testosterone from an Endocrinologist for about 18 months.

My testosterone is now 14.0nmol. I understand that this falls on the low end of the category as normal levels for my age group (41). My endo will not give me Testosterone anymore. I am extremely active, lift heavy 5 times a week, work in active outdoor employment and in my free time am surfing/playing sport etc. I eat VERY healthy. I consider this to still be low for me, as i am not your average 41 year old and i dont think i should be compared on a list of 41 year olds, who mostly are fat and lazy. I want to be optimal.

So my question is.... how do i go about getting Testosterone another way if my endocrinologist (Who is absurdly fat and unhealthy himself) wont give it to me? Is there online endo's who are more modern and dont use a flat scale for everyone?

Thank you for your time.

- Researched hypogonadism and its causes, including testicular damage. Found out my T was extremely low. Got on Testosterone from an Endocrinologist for about 18 months.

My testosterone is now 14.0nmol. I understand that this falls on the low end of the category as normal levels for my age group (41).


You have been on TTh for 18 months.

How do you feel overall?

What is your protocol (formulation/dose/injection frequency)?

If you are using transdermal how many hours post-application were labs done?

If you are using injectable esterified T how many days post injection were labs done?

This is critical!

Keep in mind that although TT is important to know FT is what truly matters as it is the active unbound fraction of T responsible for the positive effects.

The only way to know where your FT level truly sits would be having it tested using what would be considered the most accurate assay the gold standard Equilibrium Dialysis.

If you do not have access to such (highly doubtful) if you reside in the US than you would need to use/rely upon the linear law-of-mass action Vermeulen (cFTV).

Free & Bioavailable Testosterone calculator

Yes it tends to overestimate but nothing to fret over!


* However, the Vermeulen formula exhibits suboptimal accuracy and tends to overestimate measured free T by 20–30%.

* Calculated free T using high-quality T and SHBG assays has been considered the most useful for clinical purposes [99]. All algorithms suffer from some inaccuracies, including the variable quality of SHBG IAs [100], not replicating the non-linear nature of T-SHBG binding, different and inaccurate association constants for SHBG and albumin binding [101], and variable agreement with equilibrium dialysis results [99,100]. However, until further developments in the field materialize, the linear model algorithms [in particular, the most used Vermeulen equation [102]] appear to give, despite a small systematic positive bias, acceptable data for the clinical management and research[37,103].

 

[MickD84]

I very much appreciate the response, but a lot of it went over my head. Ill try my best.

How do you feel overall? Not too bad. Though i lift heavy weights 5 times a week, and have done for almost 3 years and struggle to put on muscle in comparison to others. I also eat a high protein diet and take supplements to ensure i get twice my body weight in protein per day. I have also tried bulking. Its frustrating to think that i am putting in the same amount of effort as the guy working out next to me, but if his T is double mine, he will build muscle faster.

What is your protocol (formulation/dose/injection frequency)? - I was getting Reandron once every 3 months. To be honest i dont really know how much... just the whole (tiny) bottle. I just did what i was told.

If you are using transdermal how many hours post-application were labs done? Not transdermal, syringed in.

If you are using injectable esterified T how many days post injection were labs done? Bloodwork was only ever done just before my next injection. So it was done about 2 and a half months after my injection

This is critical!

Keep in mind that although TT is important to know FT is what truly matters as it is the active unbound fraction of T responsible for the positive effects.

The only way to know where your FT level truly sits would be having it tested using what would be considered the most accurate assay the gold standard Equilibrium Dialysis.

If you do not have access to such (highly doubtful) if you reside in the US than you would need to use/rely upon the linear law-of-mass action Vermeulen (cFTV). - I am in Australia

 

[madman]

I very much appreciate the response, but a lot of it went over my head. Ill try my best.

How do you feel overall? Not too bad. Though i lift heavy weights 5 times a week, and have done for almost 3 years and struggle to put on muscle in comparison to others. I also eat a high protein diet and take supplements to ensure i get twice my body weight in protein per day. I have also tried bulking. Its frustrating to think that i am putting in the same amount of effort as the guy working out next to me, but if his T is double mine, he will build muscle faster.

What is your protocol (formulation/dose/injection frequency)? - I was getting Reandron once every 3 months. To be honest i dont really know how much... just the whole (tiny) bottle. I just did what i was told.

If you are using transdermal how many hours post-application were labs done? Not transdermal, syringed in.

If you are using injectable esterified T how many days post injection were labs done? Bloodwork was only ever done just before my next injection. So it was done about 2 and a half months after my injection

This is critical!

Keep in mind that although TT is important to know FT is what truly matters as it is the active unbound fraction of T responsible for the positive effects.

The only way to know where your FT level truly sits would be having it tested using what would be considered the most accurate assay the gold standard Equilibrium Dialysis.

If you do not have access to such (highly doubtful) if you reside in the US than you would need to use/rely upon the linear law-of-mass action Vermeulen (cFTV). - I am in Australia

With such a long acting ester Nebido/Reandron (Testosterone undecanoate) a not so stellar trough (lowest point) before your next injection would be expected due to the PK/dose/injection frequency.

Cmax will be much higher!

Even then over the 12 week injection interval Cmax will be achieved 7 days post-injection then T levels will start to gradually decline over the following weeks remaining within the physiological range until your next injection.

The main advantage of injectable TU would be minimal injection frequency due to the PK while still achieving stable serum levels its main downfall is that if one needs to make a dose adjustment it will take much longer to see changes in T levels due to the PK.

The majority of men on TTh are injecting the most commonly used esters TC or TE whether once weekly or split into more frequent injections as in twice-weekly, M/W/F, EOD or daily.

Easy to manipulate a protocol when using short (TP) or medium acting esters (TC/TE) let alone achieve a high-end/high trough and if your goal is to take advantage of Ts anabolic properties you can easily achieve a higher steady-state/trough FT.

Yes there are some men who inject lower doses of TU more frequently as they may not have an option to use another ester but your best bet would be trying to get your hands on some TC or TE.

Unfortunately in some countries injectable TU or Sustanon are the only esters prescribed so in such case you would need to seek out a UGL source.




Steady state conditions

* Following repeated i.m. injection of 1000 mg testosterone undecanoate to hypogonadal men using an interval of 10 weeks between two injections, steady-state conditions were achieved between the 3rd and the 5th administration. Mean Cmax and Cmin values of testosterone at steady state were about 42 and 17 nmol/l, respectively. Post-maximum testosterone levels in the serum decreased with a half-life of about 90 days,which corresponds to the release rate from the depot.








Treatment of Male Hypogonadism With Testosterone Undecanoate Injected at Extended Intervals of 12 Weeks: A Phase II Study (2002)
SIGRID VON ECKARDSTEIN AND EBERHARD NIESCHLAG


ABSTRACT

This paper reports the result of an open-label, nonrandomized clinical trial investigating the efficacy and safety of an injectable preparation of testosterone undecanoate (TU) dissolved in castor oil and given over a 3.2-year period. In a previous study we demonstrated that injections of TU every 6 weeks resulted in satisfactory substitution but a tendency toward testosterone accumulation. Here we investigate prolonged TU treatment at extended injection intervals in 7 hypogonadal men. Injections were given at gradually increasing intervals between the fifth and 10th injection, and from then on every 12 weeks. Steady state kinetics were obtained after the 13th injection. Well-being, sexual activity, clinical chemistry, prostate volume, and prostate-specific antigen (PSA) and serum hormone levels were monitored. Patients were clinically well adjusted throughout the study. Before the next injection, testosterone, dihydrotestosterone, and estradiol levels were mostly within the normal range and showed a tendency to decrease with increasing injection intervals. Body weight, hemoglobin, serum lipids, PSA, and prostate volume did not change significantly during the 3.2 years of treatment. PSA levels were always within the normal limit. Maximal testosterone levels during steady state kinetics were measured after1 week with 32.0 ± 11.7 nmol/L (mean 6 SD). Before the last injection, mean testosterone concentrations were 12.6 ± 3.7 nmol/L. Compared with conventional testosterone enanthate or cypionate treatment requiring injection intervals of 2–3 weeks and resulting in supraphysiological serum testosterone levels, injections of TU at intervals of up to 3 months offer an excellent alternative for substitution therapy of male hypogonadism.




Results

Testosterone and Free Testosterone

Testosterone serum levels and calculated free testosterone levels obtained before injections are shown in Figure 1. During the 6-week injection interval, testosterone levels increased initially from 5.2 ± 3.1 nmol/L to 23.8 ± 7.8 nmol/L after patients had received 4 injections in 6 weeks. With extended injection intervals, preapplication testosterone levels decreased and were just at the lower limit of normal, with 12.6 ± 3.7 nmol/L before the last injection. A comparable pattern was observed for calculated free testosterone levels, which rose to 573 6 202 pmol/L after the 6-week period, and then returned to the lower limit of normal (291 ± 93 pmol/L) after 8 injections had been performed at 12-week intervals.

Maximum steady state kinetics for levels of testosterone and free testosterone were reached after 1 week. The mean maximum concentration for testosterone was 32 nmol/L, ranging from a minimum of 15.6 to a maximum of 44.3 nmol/L. A comparable pattern was observed for free testosterone levels, with a mean of 787 pmol/L (Table3). Initial kinetics obtained in 14 subjects after the first injection of TU and steady state kinetics in the current trial are shown in Figure 2.



Figure 2. Serum testosterone after a single injection of 1000 mg TU in 14 untreated hypogonadal men (Behre et al, 1999) (open circles) and during treatment with TU for 102 weeks (closed circles). Values are given as means 6 SD. Dotted lines indicate normal limits.

Intramuscular Testosterone Undecanoate: Pharmacokinetic Aspects of a Novel Testosterone Formulation during Long-Term Treatment of Men with Hypogonadism (2004)
M. SCHUBERT, T. MINNEMANN, D. HU¨ BLER, D. ROUSKOVA, A. CHRISTOPH, M. OETTEL,M. ERNST, U. MELLINGER, W. KRONE, AND F. JOCKENHO¨ VEL


The present study shows that im TU given at 12-wk intervals is an attractive formulation for T supplementation in hypogonadism. Only four im injections per year without any further drug application in between might be very appealing to active men requiring permanent substitution of T instead of daily gel administration. The first multiple-dose pharmacokinetic studies using 1000 mg per injection of this new TU formulation proposed an injection interval of 6 wk. Here we demonstrate that injecting 1000 mg TU every 12 wk is sufficient to maintain normal T and estrogen levels in hypogonadal men, without causing local or systemic adverse side effects using this new formulation (19,20). The only prerequisite consists of either two to three initial loading doses at 6- and 9-wk intervals at the start of T substitution or two doses at 8-wk intervals when switching from short-acting preparations to TU.








Nebido: a long-acting injectable testosterone for the treatment of male hypogonadism (2005)
Lindsey Harle, Shehzad Basaria & Adrian S Dobs†


3. Chemistry of testosterone undecanoate

TU (Nebido®) is a semisynthetic systemic androgen with a molecular weight of 456.7 Da. It is a fatty acid ester, which makes it more lipophilic and results in slow absorption. TU has a prolonged half-life in comparison with other testosterone preparations due to its longer and hydrophobic sidechain (consisting of 11 carbon atoms compared with 7 in other esters; Figure 1) [4]. TU is currently not approved for use in the US, but is prescribed in Europe for the treatment of male hypogonadism.




4.2 Testosterone undecanoate

Oral TU is dissolved in oil and encapsulated in soft gelatin; each capsule containing TU 40 mg. Because of the aliphatic side chain, TU is absorbed from the gut with lipids in the lymphatic system, bypassing hepatic metabolism and deactivation [6]. Maximal serum testosterone values are reached 2 – 6 h after ingestion, and 85% of oral TU is eliminated in the urine or faeces within 3 – 4 days. Doses of 120 – 240 mg/day (divided three-times daily) of oral TU results in normal serum testosterone values in most patients [7,8].

Intramuscular TU is administered in a castor oil depot in order to decrease absorption rate. TU has a longer aliphatic side chain than other testosterone esters (11 versus 7 carbons) , further slowing its absorption and increasing its half-life. Treatment with testosterone 1000 mg in 4 ml castor oil has been evaluated in several studies in order to determine half-life, maximum concentration (Cmax) and dosing frequency. A trial by Nieschlag evaluated the effect of TU 1000 mg injection every 6 weeks for 4.5 months [9]. Serum testosterone values remained above the lower limit of normal throughout the trial and showed a trend toward increased serum testosterone levels. Cmax was seen following the final injection, and was slightly supraphysiological at 40.8 ± 3.8 nmol/l (Figure 2).
A trial by Schubert et al. comparing TU with TE showed TU to result in significantly higher trough testosterone values than TE, with a mean serum testosterone level of 16.17 nmol/l with 12-week injection intervals [4]. In addition, it was demonstrated that patients receiving TE could be transitioned to TU without interruption in therapy, but with an additional loading dose of TU 2 × 1000 mg every 8 weeks after switching from the short acting TE to TU. Based on these findings a dosing regimen of 1000 mg every 12 weeks has been suggested and evaluated to be effective and safe over a 3-year period [10]. This study evaluated the use of 9 doses of TU at gradually increasing intervals from 6 to 12 weeks. Patients were then maintained on the 12-week regimen for 60 weeks. Cmax was 32.0 ± 11.7 17 nmol/l and half-life was 70.2 ± 21.1 days. These steady-state pharmacokinetic values are considerably higher than those calculated based on a single dose and more comparable to clinical outcomes. Values remained within the normal range without severe oscillations at 12-week dosing intervals.

In order to reach steady-state conditions as soon as possible, it is recommended to begin therapy with a shorter interval of 6 weeks as a loading dose and then, from the second injection onwards, administer TU every 12 weeks.








Testosterone depot injection in male hypogonadism:a critical appraisal (2007)
Aksam A Yassin
Mohamed Haffejee


Review of pharmacology, mode of action, pharmacokinetics of testosterone depot injection

In search of a better intramuscular long-acting testosterone preparation for male contraception, the world health organization (WHO) Special Programme of Research, Development and Research Training in Human Reproduction initiated search activities for identification of suitable fatty acid side chains for esterification of T (Crabbe et al 1980). It appeared that T esterified with TU showed more favorable long-term kinetics (Herz et al 1985; Behre et al 2004). The first TU preparation was developed in China (Gu et al 2003; Zhang et al 2006). Unfortunately, the injection volume of 8 mL for 1000 mg TU caused problems at the injection site. Subsequently, by use of a special galenic formulation based on benzyl benzoate and refined castor oil, Jenapharm/Schering were able to develop a suitable intramuscular TU preparation with a volume of 4 mL containing 1000 mg TU. Intramuscular TU is currently not approved for use in the US, but is prescribed in Europe, Latin America, and Asia under the trade name Nebido® (Bayer Schering Pharma AG, Berlin, Germany), and in Australia and Spain under the trade name Reandron 1000® (Bayer Schering Pharma AG, Berlin, Germany) for the treatment of male hypogonadism.




Toxicology and pharmacology

The active pharmacological principle of TU is testosterone itself. After entering the peripheral circulation, TU (molecular weight 456.7 Da) is hydrolyzed to T which may then exert its androgenic activity (Horst et al 1976). Therefore, in principle, the toxicology of TU is the same as for other cleavableT fatty acid esters such as T propionate (3 carbon atoms), T enanthate (7 carbon atoms), or T cypionate (8 carbon atoms). In contrast to these fatty acid esters the kinetics for side chain cleavage of the saturated aliphatic fatty acid undecanoic acid with 11 carbon atoms turned out to be considerably longer,permitting much longer injection intervals, at the same time as preventing supra- or sub-physiological serum T levels.

TU had been available as an oral preparation for more than 30 years. It is well-tolerated, but the bioavailability of T leaves much to be desired. It requires careful dosing at least two times a day and it must be taken with fatty meals in order to achieve acceptable plasma T levels (Bagchus et al 2003).

Pharmacokinetics of injectable depot TU: The relationships between intramuscular TU dose ( 31, 62.5, 125, 250, and 500 mg/kg body weight s.c.) and T serum levels were investigated in male rats (Callies et al 2003). A single injection of 125 mg TU/kg body weight is effective in inducing physiological T levels in orchiectomized rats for a minimum of 4-weeks. High dose TU ( 500 mg/kg body weight) given as a single injection results in supraphysiological T serum concentrations for upto 6-weeks in non-orchiectomized animals. TU was superior to other preparations releasing T (T pellets s.c. T filled s.c.Silastic® [Dow Corning Corp.] implants, s.c. testosterone propionate) in inducing physiological T levels.

Partsch et al (1995) compared T serum levels after single intramuscular injections of 10 mg TU or T enanthate (TE)/kg bodyweight in 5 long-term orchidectomized cynomolgus monkeys (Macaca fascicularis). For pharmacokinetic characteristics such AUC (4051 vs 1771 nmol x h/L), residence time (41 vs 12 days), terminal half-life (26 vs 10 days), maximal T concentration (73 vs 177 nmol/L), and time at maximal T concentration (11 vs 1 days), TU showed pharmacokinetic and pharmacodynamic properties clearly superior to those of TE. Animals treated withTU also showed a significantly longer ejaculatory response (14-weeks ) than those treated with TE (7-weeks).




Pharmacokinetics in men

The first detailed pharmacokinetic investigation of the injectable TU preparation manufactured in China (Zhang et al 1998), administering 2 single doses in hypogonadal men. Eight patients with Klinefelter’s syndrome received either 500 mg or 1000 mg of TU by intramuscular injection; 3 months later, the other dose was given to each of the participants. Every week or every second week after the injections, the serum total T concentrations were measured. The whole observation period was only 8 or 9-weeks. The single dose injections maintained serum T levels within the normal range for at least 7-weeks without immediately apparent side effects. Of considerable interest was the observation that the pharmacokinetic profiles of T were different when 500 mg TU was given as the first injection or as the second one. Some what unexpectedly, the peak T values obtained were lower when the 500 mg dose given as the second injection, compared with when the 500 mg dose was given first. The authors speculate that long-term hypogonadism of these men may have induced faster cleavage or clearance mechanisms for TU and T by the time of the second injection. Another explanation proposed was that the residual endogenous T is suppressed by the first injection (decrease of LH and FSH), and that after the second injection, only exogenous T was measured.

In a following study (Nieschlag et al 1999) 13 hypogonadal men received 4 intramuscular injections of TU at 6-week intervals. T serum levels were never found to lie below the lower limit of normal, and only briefly after the 3rd and 4th injection were T serum levels above the upper limit of normal (Figure 1) while values peak and trough levels increased over the 24-week observation period. Serum estradiol and DHT followed the same pattern, not exceeding the normal limits. In order to better establish (von Eckardstein and Nieschlag 2002) suitable injection intervals for TU, 7 hypogonadal men received injections at gradually increasing intervals between the 5th and 10th injection (starting with 6-weeks injection interval) and from then on every 12-weeks. Steady state kinetics were assessed after the 13th injection. Cmax was 32.0 ± 11.7 nmol/L and half-life was 70.2 ± 21.1days. The mean Cmax of 32 nmol/L seen during steady-state with TU administration was lower than that achieved by Testogel® (Bayer) 100 mg/day (37.5 nmol/L); however, it was higher than with Testogel® 50 mg/day (28.8 nmol/L) and Androderm® (Watson Pharmaceuticals, Inc.,) patch 5mg/day (26.5 nmol/L). Before the next injection, the serum levels for T and its metabolites DHT and estradiol were mostly within the normal (eugonadal) range and showed a tendency to decrease with increasing injection intervals. The study concluded that after initial loading doses at 0 and 6-weeks, injection intervals of 12-weeks establish eugonadal values of serum testosterone in almost all men. A later study (Yassin and Saad 2005) analyzing 58 hypogonadal men receiving TU treatment every 3 months did not report elevations of DHT levels exceeding the physiological threshold.

In an open label, randomized, prospective study (Schubert et al 2004), TU (1000 mg TU 3 times every 6-weeks, thereafter every 9-weeks) was compared with TE (250 mg every 3-weeks) in 40 hypogonadal men. In contrast to the group treated with TE, trough T levels (measured immediately before the new injection) in patients receiving TU remained within the physiological (eugonadal) range. This study was extended as a follow-up study for approximately 2.5 years of treatment (Morales et al 2006). All the patients in this study phase received 1000 mg TU every 12-weeks (the patients who had earlier received TU)) or 2 x 1000 mg TU every 8-weeks followed by 1000 mg TU every 12-weeks (the patients who had earlier received TE ). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 ± 5.2 to 16.5 ± 8.0 nmol/L) and estradiol (ranging from 98.5 ± 45.2 to 80.4 ± 14.4 pmol/L). For T therapy with TU the authors recommended an initial loading dose of 3 × 1000 mg TU every 6-weeks followed by 1000 mg TU every 12-weeks. On the basis of pharmacokinetic studies the conclusion was reached that patients receiving TE could be switched to TU without interruption in therapy, but with an additional loading dose of TU 2 × 1000 mg every 8-weeks after switching from the short-acting TE to TU (Schubert et al 2004; Nieschlag 2006).

Clinical long-term experience up to 120-weeks was published in 2004 (Schubert et al 2004). Twenty-six hypogonadal patients received TU (1000 mg TU/4mL) in a first stage of the study in weeks 0, 6, 16, 26, and 36, followed by an additional stage of up to 120-weeks with injections every 12-weeks. The supranormal peak concentrations of total and free T occurred 2-weeks after the first injection, then a decrease to within the physiological range was observed. At the end of the study, during washout period, serum T levels declined to the low pre-treatment levels 14-weeks after the final injection. A parallel increase of 17β-estradiol levels was seen, but there was an earlier decrease to pre-treatment levels by 4-weeks after the last injection. Serum LH and FSH were suppressed during the treatment period, while sex hormone binding globulin (SHBG) remained stable. The latter is probably an expression of the physiological range of achieved plasma testosterone levels; administration of high dose testosterone leads to a fall in plasma SHBG levels (Anderson et al 1996).

Serum prostate specific antigen (PSA) rose from 0.660 to 0.976 ng/mL (p < 0.01) after 120-weeks, but did not exceed the normal range. Prostate volume increased from 19.6 to 26mL (p < 0.05). Osteocalcin rose from 0.734 to 1.049 nmol/L(p < 0.01). Bone mineral density (BMD) did not change.

Standard laboratory tests and uroflow did not change. Sexual interest (assessed by use of the AMS questionnaire) increased (reviewed in Harle et al 2005).

There is now long-term experience of up to more than 8 years with TU in 22 hypogonadal men (Zitzmann 2006). Individual dosing intervals ranged from 10 to 14-weeks. Serum trough levels of T were generally within the low-normal range, indicating sufficient substitution. In contrast to short acting T esters, sensations of fluctuations in androgen serum concentrations were rarely observed. When they were, they occurred during the last 2-weeks before the next injection, indicating loss of androgenic psychotropic effects. Summarizing two key studies (von Eckardstein and Nieschlag 2002; Schubert et al 2004) the following administration regimen i srecommended for TU therapy in hypogonadal men: After the first injection of 1000 mg TU, the second injection of 1000mg TU is to be administered 6-weeks after the first injection (loading dose) followed by injections every 12-weeks. While this schedule will generally be adequate, an individualization of TU therapy may be desirable (Zitzmann 2006). If the T serum concentration before the 4th injection lies between 10 and 15 nmol/L then the injection interval should be every 12-weeks. Should the T serum concentration at this time be lower than 10 nmol/L, then the injection interval is shortened to every 10-weeks. If the T level is greater than15 nmol/L, then the injection interval should be extended to every 14-weeks. Additionally, clinical symptoms should be considered for individualization of injection intervals with TU therapy.The loading dose of TU achieved by the first two injections with an interval of 8-weeks is also recommended for patients who are being transferred from short-acting T injections (eg,testosterone enanthate 250 mg) to treatment with TU.