If natural Testosterone peaks at 10AM, 12 hours later?

[BackToRegular]

From what I've gathered online, injected testosterone peaks 24hrs after injection. Additionally I've read natural testosterone peaks at 10AM. To minimize peaks and troughs does it make sense to inject at 10pm so the peak is exactly 24hrs later and 12hrs between both natural peaks?

 

[Cataceous]

The Antares clinical trial along with work by Nieschlag suggest that for cypionate and enanthate the peaks occur in under 12 hours after injections. With propionate it is likely much shorter, probably in the range of 2-6 hours.

Keep in mind that testosterone injections will completely suppress natural production. Over time there will be no more natural peaks, only the one after each injection.

If you want to minimize hormonal variations then inject enanthate or cypionate subcutaneously at least every-other-day. For most this results in pretty flat levels. Some even go with daily injections, but that's probably overkill with these longer esters.

With injections, the best emulation of normal daily variations in serum testosterone might be provided by daily, early morning injections of a combination of propionate and a longer ester.

 

[BackToRegular]

The Antares clinical trial along with work by Nieschlag suggest that for cypionate and enanthate the peaks occur in under 12 hours after injections. With propionate it is likely much shorter, probably in the range of 2-6 hours.

Keep in mind that testosterone injections will completely suppress natural production. Over time there will be no more natural peaks, only the one after each injection.

If you want to minimize hormonal variations then inject enanthate or cypionate subcutaneously at least every-other-day. For most this results in pretty flat levels. Some even go with daily injections, but that's probably overkill with these longer esters.

With injections, the best emulation of normal daily variations in serum testosterone might be provided by daily, early morning injections of a combination of propionate and a longer ester.

Thank you Cataceous, I suppose if you fully suppress your natural production then you control the peaks. With HCG injection would you still have the natural peak at 10AM?

 

[madman]

I would not dwell on the one Nieschlag study that showed T levels peaking under 12 hrs as there are numerous other studies stating 24 hr.

 

[Cataceous]

... With HCG injection would you still have the natural peak at 10AM?

No, and natural peaks occur closer to 8 am. Although hCG can stimulate testosterone peaks, its long half-life means that it's not simple to predict when they will occur.

I would not dwell on the one Nieschlag study that showed T levels peaking under 12 hrs as there are numerous other studies stating 24 hr.

That's why I mentioned the Antares study as well. It highlights a potential flaw in studies finding the peak at later times: If the HPTA is not suppressed then the first dose of exogenous testosterone has a blunted rise in testosterone, delaying the peak by 12+ hours. We see that after five weeks of regular administration the peak has shifted to under 12 hours post-injection.

 

[madman]

No, and natural peaks occur closer to 8 am. Although hCG can stimulate testosterone peaks, its long half-life means that it's not simple to predict when they will occur.


That's why I mentioned the Antares study as well. It highlights a potential flaw in studies finding the peak at later times: If the HPTA is not suppressed then the first dose of exogenous testosterone has a blunted rise in testosterone, delaying the peak by 12+ hours. We see that after five weeks of regular administration the peak has shifted to under 12 hours post-injection.

True but there are still some older studies using weekly injections that have shown once steady state is achieved that T levels peak close to 24 hrs.


Treatment of Male Hypogonadism with Testosterone Enanthate*
PETER J. SNYDER AND DAVID A. LAWRENCE


Snyder and Lawrence (1980) administered 100 mg/wk (n = 12), 200 mg/2 wks (n = 10), 300 mg/3 wks (n = 9) and 400 mg/4 wks (n = 6) testosterone enanthate to hypogonadal patients during a study period of three months. Blood was drawn during the last injection period, when steady state had been reached, every day (100 mg/wk) up to every fourth day (400 mg/4 wks). Similar to the computer simulation described above for 250 mg testosterone enanthate and injection intervals of one to four weeks, initial supraphysiological testosterone serum levels were seen shortly after injection. In the 100 mg/wk treatment group, where daily blood sampling was performed, mean peak serum concentrations were seen 24 h after injection. Comparable to the results of the computer simulation, after injection of 200 mg/2 wks testosterone enanthate, following initial supraphysiological testosterone serum levels, values fell to progressively lower values before the next injection, eventually reaching the lower normal limit (Snyder and Lawrence 1980). Similar results were described after injection of 300 mg/3 wks or 400 mg/4 wks testosterone enanthate. The authors conclude that the testosterone enanthate doses of 200 mg have to be injected every two weeks or doses of 300 mg every three weeks to guarantee effective substitution therapy.




Here is one of the first published studies (pilot) from Canada using subcutaneous injections of Delatestryl (testosterone enanthate) in men.


Subcutaneous administration of testosterone A pilot study report


ABSTRACT

Objective: To investigate the effect of low doses of subcutaneous testosterone in hypogonadal men since the intramuscular route, which is the most widely used form of testosterone replacement therapy, is inconvenient to many patients.

Methods: All men with primary and secondary hypogonadism attending the reproductive endocrine clinic at Royal Victoria Hospital, Montreal, Quebec, Canada, were invited to participate in the study. Subjects were enrolled from January 2002 till December 2002. Patients were asked to self-administer weekly low doses of testosterone enanthate using 0.5 ml insulin syringe.

Results: A total of 22 patients were enrolled in the study. The mean trough was 14.48 ± 3.14 nmol/L and peak total testosterone was 21.65 ± 7.32 nmol/L. For the free testosterone the average trough was 59.94±20.60 pmol/L and the peak was 85.17 ± 32.88 pmol/L. All of the patients delivered testosterone with ease and no local reactions were reported.

Conclusion: Therapy with weekly subcutaneous testosterone produced serum levels that were within the normal range in 100% of patients for both peak and trough levels. This is the first report, which demonstrated the efficacy of delivering weekly testosterone using this cheap, safe, and less painful subcutaneous route. Saudi Med J 2006;



*The starting dose of testosterone enanthate was 25-50 mg each week and then we adjusted according to the peak and trough levels and patient symptoms. The Hospital Ethics Committee granted institutional review board approval.



Results. A total of 22 hypogonadal men were enrolled in the study. The mean age was 33 ± 13 years with an age range of between 15 and 55 years. The mean subcutaneous weekly testosterone dose was 55 ± 27 mg with a minimum of 25 mg and a maximum of 100 mg. Age, hypogonadal diagnostic category, prior treatment regimen, and sex hormone levels are summarized in Table 1. Following initiation of treatment, the peak total and free testosterone levels were within the normal range both before (trough) and following injection (peak). The results are shown in Table 1 and Figures 1a and 1b. The mean total testosterone prior to injection was 14.5 ± 3.14 nmol/L and 21.7 ± 7.32 nmol/L the day following the injection. For the free testosterone, the mean trough level was 59.9 ± 20.6 pmol/L and the peak one day later was 85.2 ± 32.9 pmol/L. These results were within the normal male range for our laboratory (total testosterone 10-38.5 nmol/L, and free testosterone 31.2-162.9 pmol/L). All the patients stated that, subcutaneous injections were easy to use, and well tolerated. None of them reported any local reactions due to subcutaneous injections such as bruising, erythema, pain, swelling, and nodules.




Mind you I will say that Tmax can be achieve anywhere from 8-24 hrs.

Even when looking at the major study by Antares using subcutaneous T injections using Xyosted (testosterone enanthate) which was posted in an earlier thread:


A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector.
Kaminetsky JC, McCullough A, Hwang K, Jaffe JS, Wang C, Swerdloff RS




Subcutaneous Injection



Overall (N=137) - Mean (SD) for Tmax (h) 22.8 (24.44), Median (Q1,Q3) 11.9 (8.98, 35.15)

Look at the difference in the Mean (SD) and Median (Q1,Q3) for Tmax (h) between the 50--->100mg dose.

Cavg 0–168h, average concentration over the 7-day dosing interval (0–168 hours); Cmax, maximum (peak) blood concentration; Cmin, minimum blood concentration; PK, pharmacokinetic; Tmax, time to reach maximum blood concentration; TT, total testosterone.

*The fluctuation (peak-to-trough) ratios were 1.813 for the overall study population and 1.854, 1.758, and 2.025 for the 50-, 75-, and 100-mg dose groups, respectively.

 

[Cataceous]

True but there are still some older studies using weekly injections that have shown once steady state is achieved that T levels peak close to 24 hrs.
...

I just skimmed through the studies in your post, so I could have missed it, but I'm not seeing indications that in the earlier studies the readings were taken before 24 hours post-injection. So naturally 24 hours is where they find the peak, even though it easily could have occurred earlier. In contrast, the Nieschlag and Antares studies have measurements in the first 12 hours that are peaks.

 

[madman]

I just skimmed through the studies in your post, so I could have missed it, but I'm not seeing indications that in the earlier studies the readings were taken before 24 hours post-injection. So naturally 24 hours is where they find the peak, even though it easily could have occurred earlier. In contrast, the Nieschlag and Antares studies have measurements in the first 12 hours that are peaks.

Doubtful that levels would have been tested <24 hr post injection.

The 52 week Antares study does show a large difference in the Mean (SD) and Median (Q1,Q3) for Tmax (h) between the 50 and 100mg dose.


50 mg dose Tmax in hours - Mean (SD) 25.3 (20.32) and Median (Q1,Q3) 12.00 (8.90, 35.55)

100 mg dose Tmax in hours - Mean (SD) 31.6 (36.17) and Median (Q1,Q3) 24.1 (8.97, 35.95)


I still think Tmax is achieved anywhere from 8-24 hr post injection.

I know there are even nandrolone studies showing that the addition of BOH (benzyl alcohol) which is commonly used in many injectable preparations has been shown to cause two distinct peaks.....one early and another days later as the BOH apparently causes a large bolus of the prodrug to be released early.


From my previous thread:Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study

I did state:

Notice when looking at the graph for Panel A.....during weeks 6 and 12 testosterone levels peak 10 hrs post injection followed by dip and than a second peak at 36 hrs when using testosterone enanthate (TE Auto-Injector).