Is the feeling of "well being" on TRT, dosage dependent?

[John O'Connor]

You did show me that the most credible research found a half-life of about five days for testosterone cypionate. In addition, there have been a few instances of guys reporting two testosterone measurements in an injection cycle, and these have jibed with the five-day half-life figure. So yes, on a 3.5 day cycle there's usually going to be a pronounced trough, and the peak could be as much as 50-60% higher.

I also agree that serum testosterone peaks in the first 12 hours post-injection, and maybe much less. With propionate, at two to three hours post-injection I see quite high values, which are around the predicted peak. In modeling the pharmacokinetics of testosterone esters one finds that the major influence on time-to-peak is the half-life of pure testosterone in serum; time-to-peak is relatively insensitive to the half-life of the ester itself.

I stand corrected on the half life being attributed to the different oils used. Looks like it has more to do with the number of carbons attached to enanthate vs cypionate, being 7 and 8 carbons respectively. As for the peak timing for most of the sources seem to say its 48 to 72 hours for cypionate. Half-life of 8 days for cypionate is based on the manufacturer. Cataceous, if you have a study that shows cypionate peaks at 12 hours, I'd love to see it. There is a lot of contradictory information out there on the web. I did find a study suggesting cypionate peaks at 4-5 days, and lasts only 8 or 9 days, but that study is from 1987 and only had 11 participants. Unfortunately many other studies seem to reference it 2 to 3 decades later.

Madman mentioned enanthate and cypionate are basically interchangeable. I only have experience with cypionate, but while I've read enanthate has a 7 day half life and cypionate an 8 day half life, similar to the number of carbons attached to each, even Defy Medicals site says enanthate halflife is 4 to 5 days, and cypionate is 8. Just lots of contradictory information out there. Different types of injectable testosterone

Note I'm not claiming defy medicals website is correct or incorrect, just showing the contradictory information is everywhere.

On a personal note when I started TRT once weekly cypionate 100mg doses my trough on day 8 just prior to next injection was around 550 while my peak at 72 hours was 1100. Since changing to 3 injections per week my levels have been consistent no matter when my blood is drawn. Note If I know I'm having labs done tomorrow morning, but my next injection is tonight I will postpone it until after the blood draw as I do agree there is some initial spike immediately following injection. I attribute that to the oil not 100% absorbing into the muscle tissue upon injection. But that is just based on my personal experience as the first injection I ever took was 100mg in a single dose and within 2 hours my pupils were significantly dilated and I felt a huge rush of energy.

 

[madman]

Confused about Testosterone Enanthate Half Life

Am I confused about Enanthate being a faster acting ester than Cyp? Like in the middle between Prop and Cyp which I had a bad experience with (My daily Testosterone Propionate diary) Seems like I have it stuck in my head with Test-E being more about ~48hrs but I can't seem to find that info...

www.excelmale.com

COMPARISON OF TESTOSTERONE, DIHYDROTESTOSTERONE, LUTEINIZING HORMONE, AND FOLLICLE-STIMULATING HORMONE IN SERUM AFTER INJECTION OF TESTOSTERONE ENANTHATE OR TESTOSTERONE CYPIONATE



DISCUSSION

Injection of either testosterone enanthate or testosterone cypionate in equivalent doses yielded identical serum testosterone concentrations both in terms of maximal concentrations and in terms of duration of elevation above basal levels. Maximal and supraphysiologic levels were achieved as early as the 1st day after injection, and these values had returned to basal concentrations on day 10. There were also no differences in the conversion of testosterone to DHT and in the suppression of LH and FSH observed_ Thus, both esters show the same pharmacokinetic properties and appear to be equally useful for clinical purposes.








Pharmacology of testosterone preparations
H.M. Behre, C. Wang, D.J. Handelsman and E. Nieschlag



14.3.6.2 Testosterone enanthate

Single-dose pharmacokinetics of testosterone enanthate after intramuscular administration of 250 mg testosterone enanthate to seven hypogonadal patients and the best-fitted pharmacokinetic profile are shown in Fig. 14.6 (Nieschlag et al. 1976). Maximal testosterone levels in the supraphysiological range were seen shortly after injection (39.4 nmol/l, tmax = 10 h). Testosterone levels below the normal range were observed following day 12 after injection. The calculated values were 9911 nmol ∗ h/l for AUC, 8.5 d for MRT, and 4.5 d for terminal half-life (Table 14.2). Based on the pharmacokinetic parameters of single-dose pharmacokinetics multiple-dose pharmacokinetic simulations for equal doses of 250 mg testosterone enanthate and injection intervals of one to four weeks were performed. With weekly injection intervals, supraphysiological maximal testosterone serum concentrations up to 78 nmol/l are observed at steady-state shortly after injection and supraphysiological minimal testosterone serum concentrations up to 40 nmol/l just before the next injection (Fig. 14.7). Injecting 250 mg of testosterone enanthate every two weeks results in maximal supraphysiological testosterone serum concentrations of up to 51 nmol/l shortly after injection and testosterone serum levels at the lower range for normal testosterone serum concentration shortly before the next injection. If the injection interval is extended to three weeks, testosterone serum concentrations below the normal range are observed 14 days after injection. With injection intervals of four weeks, testosterone serum concentrations are in the subnormal range at week three and four and effective testosterone substitution is not guaranteed (Fig. 14.7).

The calculated testosterone serum concentrations at steady state obtained by computer simulation correspond well to the results of published studies describing multiple-dose testosterone enanthate pharmacokinetics. In a clinical trial for male contraception, 20 healthy men were injected with 200 mg/wk of testosterone enanthate for 12 weeks (Cunningham et al. 1978). Minimal serum concentrations of testosterone at steady state, i.e. the testosterone serum concentration just before the next injection, were measured at 31.2 nmol/l to 39.5 nmol/l after weekly injections of 200 mg testosterone enanthate. Very similar data were obtained in further contraceptive studies when normal men received 200 mg/wk testosterone enanthate injections for 18 months (Anderson and Wu 1996; Wu et al. 1996). The data of these studies fit well with the computer-calculated minimal testosterone serum concentrations of 40 nmol/l and maximal testosterone levels 78 nmol/l after multiple injections of testosterone enanthate at a dosage of 250 mg/wk.

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 injections 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 3 weeks to guarantee effective substitution therapy.




14.3.6.3 Testosterone cypionate and testosterone cyclohexanecarboxylate

Testosterone cypionate (cyclopentylpropionate) pharmacokinetics were compared with those of testosterone enanthate in a cross-over study involving six healthy men aged 20–29 years. Three subjects received 194 mg of testosterone enanthate, followed seven weeks later by 200 mg of testosterone cypionate and vice versa (amount of unesterified testosterone 140 mg in both preparations). The serum testosterone profiles were identical after injection of both preparations in equivalent doses, both in terms of maximal concentrations and in terms of duration of elevation above basal levels (Fig. 14.8) (Schulte-Beerbuhl and Nieschlag 1980). In a subsequent clinical study, the pharmacokinetics of testosterone cyclohexanecarboxylate were compared to the pharmacokinetics of testosterone enanthate in a single-blind cross-over study in seven healthy young men (Schurmeyer and Nieschlag 1984). After injection of either testosterone enanthate or testosterone cyclohexanecarboxylate, testosterone concentrations in serum increased sharply and reached maximum levels, 4–5 times above basal, 8–24 h after injection. During the following days a parallel decay of testosterone levels occurred after injection of either ester preparations, with testosterone serum concentrations slightly, but significantly lower after testosterone cyclohexane carboxylate injection compared to testosterone enanthate injection two, three and seven days after administration. Basal serum levels were reached seven days after testosterone cyclohexanecarboxylate administration and nine days after injection of testosterone enanthate

Because testosterone cypionate, testosterone cyclohexanecarboxylate, and testosterone enanthate had comparable suppressing effects on LH and consequently on endogenous testosterone secretion, it can be concluded from these studies in normal volunteers that all three esters with similar molecular structure possess comparable pharmacokinetics of exogenous testosterone serum concentrations. Testosterone cypionate or testosterone cyclohexanecarboxylate do not provide a more advantageous pharmacokinetic profile than testosterone enanthate. This observation is in agreement with a clinical study of replacement therapy with single-dose administration of 200 mg of testosterone cypionate in 11 hypogonadal patients (Nankin 1987).







*Keep in mind with the above studies except for one of them by Nieschlag that blood work was not taken hourly post-injection let alone prior to 24 hrs!
.

 

[madman]

The more recent Antares study using Xyosted (Testosterone Enanthate) sub-q injections that I posted a while back shows Tmax 10hrs post-injection.

 

[Cataceous]

The more recent Antares study using Xyosted (Testosterone Enanthate) sub-q injections that I posted a while back shows Tmax 10hrs post-injection.

Why does this study come up with a very long half life, 10 days?

The apparent T1/2 (SD) was 239.63 hours (59.93) for 100 mg SC TE...​

[Ref]

 

[UCFguy01]

Your feeling of well-being is ultimately dependent on your state of mind. Your hormones affect your mood, yes. We also get an increase in dopamine when we start something new such as TRT or when there is a change in protocol. That feeling of excitement and energy and change and hope or whatever it is for you. That is why we always go from “great” to “normal” after some time and the effect feels like it wears off. There is never enough dopamine.

If you have depression, more testosterone is not going to fix that. T can help to improve your motivation and energy and mood to varying degrees in people, but that is different. Depression is something that should be taken seriously and discussed with your doctor.

For me, testosterone seemed to be a really good anti-depressant. I suffered with anxiety and depression (probably due to stress) before I went on TRT. I tried antidepressants and Xanax, etc. I still always felt like a shell of a person. I'd lay on the couch tired and depressed a lot of the time. It was pretty awful.

Then i was introduced to testosterone pellets and it changed my life. My depression and anxiety went almost to zero. The depression disappeared and I would only get anxiety here and there...and it was not that awful kind of anxiety. Just a little anxious feeling. I'd say I went from 80% of the time feeling like crap to only feeling like crap 5% of the time. That's how good it worked for me. I went from a shell of my former self to the most outgoing motivated person. My friends could tell a difference and my wife could definitely tell. She loved it!! Now it's been 6 years on TRT and I don't ever plan on quitting. I keep my total T levels in the 1300-1500 range and it's been a great ride.

 

[madman]

Why does this study come up with a very long half life, 10 days?

The apparent T1/2 (SD) was 239.63 hours (59.93) for 100 mg SC TE...​

[Ref]

Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single-Use Autoinjector: A Phase II Study
Jed Kaminetsky, MD, Jonathan S. Jaffe, MD, and Ronald S. Swerdloff, MD




Most of the information we have based on the half-life (esterified T) was done using IM.

They do state T1/2 (SD) was 239.63 hours (59.93) for 100 mg SC TE

Because of rising T levels at later time points in the 50 mg arm, a reliable estimation of half‐life (T1/2) of this dose was not possible. The apparent T1/2 (SD) was 239.63 hours (59.93) for 100 mg SC TE and 172.57 hours (34.74) for 200 mg IM T


Table 2
Mean T½—h (SD) 239.63




Pharmacology of testosterone preparations
H.M. Behre, C. Wang, D.J. Handelsman and E. Nieschlag

Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects
Youwei Bi Paul J. Perry Touro University California, [email protected] Michael Ellerby Touro University California, [email protected] Daryl J. Murry




Cypionate study states the mean/median having a much shorter half-life.


DISCUSSION

Following the depot administration of TC, the PKs of tT were satisfactorily described by the one-compartmental model with first-order absorption. The limited number of samples in the absorption phase (1–2 samples per subject) prevents using a more plausible absorption model for the high lipophilicity of testosterone in an oil base and administered i.m., such as a mixed zero-order and first-order model with lag time.16 This could lead to flip-flop PKs and can cause difficulties in the estimation and interpretation of PK parameters.17 The half-life of testosterone undecanoate (TU) following oral administration is around 150 minutes,18 which is very different from the half-life estimate of 21–34 days following the i.m. injection of TU reported by Behre et al. 19 The large difference in half-lives of TU between oral and i.m. formulation suggests that flip-flop PKs are occurring with testosterone esters, which is also reported in the published literature20 and for the i.m. injection of nandrolone.21 The i.m. injection of TC is also likely to have flip-flop kinetics, in such a scenario, diffusion, and release from an oily depot site is the rate-limiting step to systemic availability.

It is difficult to calculate the PK parameters of TC using traditional noncompartmental methods, especially when the endogenous testosterone secretion rate is suppressed during the course of TC administration and the testosterone secretion rate is regulated by the LH-testosterone feedback loop system in HPG axis. Our estimated post hoc median tT half-life was 4.05 days, which is shorter than the mean reported elimination half-life of 6.9 days determined using noncompartmental analysis.11 Such inconsistency is believed to result from failure to consider endogenous testosterone production. When we assume endogenous testosterone secretion is 0 in the PPK analysis, the median estimated half-life increases to 6.87 days.

 

[rayrock1]

john o connor, what is your total testosterone and free T levels now that you are injecting e3d now? do you do IM injections?

 

[John O'Connor]

john o connor, what is your total testosterone and free T levels now that you are injecting e3d now? do you do IM injections?

Rayrock1, I'm consistently in the low 700s total test. Last lab, total testosterone was 715ng/dL, and free test was 14pg/mL.

Also Madman & Cataceous, thanks for the above studies. I have only had a few minutes to glance at them but will definitely respond in next few days.

 

[rayrock1]

Rayrock1, I'm consistently in the low 700s total test. Last lab, total testosterone was 715ng/dL, and free test was 14pg/mL.

Also Madman & Cataceous, thanks for the above studies. I have only had a few minutes to glance at them but will definitely respond in next few days.

thank you for the reply. by injecting e3d, will the total test and free t, be higher over e3.5d?assuming doseage total per week is the same? also what were the symptoms you had at 100mg/week that you decided 90 mg was better?

 

[John O'Connor]

thank you for the reply. by injecting e3d, will the total test and free t, be higher over e3.5d?assuming doseage total per week is the same? also what were the symptoms you had at 100mg/week that you decided 90 mg was better?

Rayrock1, dosing more frequently with smaller doses simply levels out your highs and lows. So for me dosing 100mg once per week had my peak at 1150+, and my trough in the 550 range. I noticed less frequent morning wood around the peak, 48-72 hour post injection time, but morning wood improved as I got closer to my trough day. I 1st tried increasing frequency but keeping weekly dose the same, so 50mg e3.5 days, but I probably only had morning wood twice per week on that regimen, with my trough level in the 900 range. My hematocrit was also getting into the 51-53 range despite donating blood it remained there. I then lowered dose to 80mg weekly, 40mg e3.5days, which brought my total T to 600 range, and brought hematocrit down too. Frequency of morning wood improved to about 5 days per week. After 6-9 months on the 80mg weekly dose, I decided to try bumping up to 90mg, 30mg 3x per week. I was able to maintain low hematocrit levels, maintain regular morning wood, and total T has been stable in the 700+ range since then. As much as I'd love to be on a higher dose for strength benefits, as I did have noticeably more power on the 100mg dose, every time I try to bump the 30mg dose up to 32 or 33mg I notice a decrease in morning wood frequency. So essentially its just been small adjustments to find the optimal dose for me. For reference, I began TRT in 2016, and as others frequently say the initial spike in hematocrit seemed to level off over the 1st 1-2 years on TRT. I have not had to donate blood over the last 2 years.

 

[rayrock1]

john, thanks for the reply. I am at the same numbers with 100mg e3.5d, so just wondering which way to go. I recently added 250iu of HCG twice weekly and I feel it helped the achy testicles but has brought me down overall, mood and libido.

 

[John O'Connor]

john, thanks for the reply. I am at the same numbers with 100mg e3.5d, so just wondering which way to go. I recently added 250iu of HCG twice weekly and I feel it helped the achy testicles but has brought me down overall, mood and libido.

Adding HCG will increase your endogenous testosterone production, although 250iu twice weekly is a fairly conservative dose. The testosterone pathway results in 2 outcomes. Testosterone either converts to estrogen, or DHT. I'm guessing you are converting more in the direction of estrogen, thus the mood issues. If labs prove that to be true, then either lower your dose, or start an AI, aromatase inhibitor, to inhibit the conversion to estrogen. Many guys here will recommend the AI, but I believe the growing concensus in recent years is to not take an AI, and instead simply lower your testosterone dosing. Don't guess though, be sure to get labs and preferably use the sensitive estradial lab.

 

[rayrock1]

john, thank you again for explaining everything. My estradiol pre TRT was 14.6. after first six weeks was 15.6. Is it possible I would need to increase my dosage?

 

[John O'Connor]

john, thank you again for explaining everything. My estradiol pre TRT was 14.6. after first six weeks was 15.6. Is it possible I would need to increase my dosage?

Sorry for the delayed response, I just noticed your message. I wouldn't think increasing it would improve your emotional struggles. From your original post, you mentioned you feel more emotional and down trodden the day before and day of injection. Has that trend held true since your original post on August 4th? Since your estradiol labs have not changed much it would be tough to blame it on estrogen. Its difficult to know if its psychosomatic reaction or due to actual changes in hormones and / or neurotransmitter levels. Since you have not been on TRT very long, giving it time, and keeping a journal of how you feel is my best advice. Maybe trying to increase or decrease dosage, or changing the frequency from twice a week to 3x per week would help level things out. At the end of the day, we all react differently and you may just have to experiment a little on your own to find the right regimen.

 

[rayrock1]

okay thanks John makes sense.