I found a TRT protocol that works

[UCFguy01]

week 3.......

Libido is on fire!!

 

[goolapsh]

week 3.......

Libido is on fire!!

So much for everyone saying pellets suck lol

 

[bixt]

- The slower steady rise of testosterone over 6-8 weeks and then the decline over 6-8 weeks

Maybe we are all looking at this the wrong way. Lets hypothesise with dopamine being responsible instead of E2, DHT etc. The slow increase of T and therefore D would allow the brain to sustain the honeymoon high, similar to Wellbutrin. The brain doesnt try to reduce dopamine / D receptors as the change is gradual.

On the other hand, cocaine for example will lead to a quick high, and then require ever higher doses or it will stop working on dopamine. Receptors get fried from quick increases in D.

Perhaps, its the gradual increase in T, and therefore D which lends itself to sustained libido on pellets? The slow return to lower levels will additionally allow the receptors to recover and be primed for the next pellet insertion.

This goes into stark contrast with the concept of 1. Stable levels (ED or E2D) or 2. The hormone rollercoaster (EW or E2W).

Its instead a gradual hormone rollercoaster, one which tricks the brain dopamine wise in sustained levels.

 

[goolapsh]

Maybe we are all looking at this the wrong way. Lets hypothesise with dopamine being responsible instead of E2, DHT etc. The slow increase of T and therefore D would allow the brain to sustain the honeymoon high, similar to Wellbutrin. The brain doesnt try to reduce dopamine / D receptors as the change is gradual.

On the other hand, cocaine for example will lead to a quick high, and then require ever higher doses or it will stop working on dopamine. Receptors get fried from quick increases in D.

Perhaps, its the gradual increase in T, and therefore D which lends itself to sustained libido on pellets? The slow return to lower levels will additionally allow the receptors to recover and be primed for the next pellet insertion.

This goes into stark contrast with the concept of 1. Stable levels (ED or E2D) or 2. The hormone rollercoaster (EW or E2W).

Its instead a gradual hormone rollercoaster, one which tricks the brain dopamine wise in sustained levels.

Yes this makes sense. Maybe we should all be taking wellbutrin lol

 

[UCFguy01]

Maybe we are all looking at this the wrong way. Lets hypothesise with dopamine being responsible instead of E2, DHT etc. The slow increase of T and therefore D would allow the brain to sustain the honeymoon high, similar to Wellbutrin. The brain doesnt try to reduce dopamine / D receptors as the change is gradual.

On the other hand, cocaine for example will lead to a quick high, and then require ever higher doses or it will stop working on dopamine. Receptors get fried from quick increases in D.

Perhaps, its the gradual increase in T, and therefore D which lends itself to sustained libido on pellets? The slow return to lower levels will additionally allow the receptors to recover and be primed for the next pellet insertion.

This goes into stark contrast with the concept of 1. Stable levels (ED or E2D) or 2. The hormone rollercoaster (EW or E2W).

Its instead a gradual hormone rollercoaster, one which tricks the brain dopamine wise in sustained levels.

I have had similar thoughts about the dopamine being the reason for the libido........ and the slow gradual release helping the dopamine levels.

It's also interesting that when I'm on pellets, the libido seems to be even higher on the way back down (roughly week 8-10'ish). Then the last few weeks I start feeling like I need more.

And I don't want to make it sound like I'm on some "honeymoon" phase. It really is just good mood, good energy, and good libido. On injections, I had the first two but never the third.

 

[UCFguy01]

Yes this makes sense. Maybe we should all be taking wellbutrin lol

......or another one of the dopamine prescription type meds that are out there? The rabbit hole never ends....

 

[UCFguy01]

I will say I'm not on here as much because I feel like I found the answer to my problems

.....and because my bitcoins are about to go to the moon!!! lol

 

[goolapsh]

I will say I'm not on here as much because I feel like I found the answer to my problems

.....and because my bitcoins are about to go to the moon!!! lol

Also how is your sleep?

 

[madman]

Maybe we are all looking at this the wrong way. Lets hypothesise with dopamine being responsible instead of E2, DHT etc. The slow increase of T and therefore D would allow the brain to sustain the honeymoon high, similar to Wellbutrin. The brain doesnt try to reduce dopamine / D receptors as the change is gradual.

On the other hand, cocaine for example will lead to a quick high, and then require ever higher doses or it will stop working on dopamine. Receptors get fried from quick increases in D.

Perhaps, its the gradual increase in T, and therefore D which lends itself to sustained libido on pellets? The slow return to lower levels will additionally allow the receptors to recover and be primed for the next pellet insertion.

This goes into stark contrast with the concept of 1. Stable levels (ED or E2D) or 2. The hormone rollercoaster (EW or E2W).

Its instead a gradual hormone rollercoaster, one which tricks the brain dopamine wise in sustained levels.

He is only 3 weeks in!

Much more involved when it comes to libido let alone erectile function than TT, FT, estradiol, DHT, prolactin.

Hate to burst your bubble but there is an initial burst release of T (small short-lived peak) within the first 2 days (48 hrs) and levels will stay elevated off the hop as there is a plateau phase lasting roughly 60 days which is then followed by a gradual decline over the following months.


*The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 ± 3.7 nmol at 0.5 ± 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 ± 2.3; day 63, 34.8 ± 2.6 nmol). Thereafter serum T gradually declined and was close to baseline concentrations on day 300.






Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men (1996)


Summary

0BJECTIVE There are advantages and disadvantages with all of the presently available types of testosterone replacement for hypogonadal men. We performed this investigation to establish detailed data about the pharmacokinetics, pharmacodynamics, feasibility, and side-effects of subcutaneously implanted testosterone (T) pellets.

DESIGN AND MEASUREMENT In a single-dose, open-label, non-randomized study, 6 T-pellets, each containing 200mg of fused crystalline T, were Implanted in the subdermal fat tissue of the lower abdominal wall of 14 hypogonadal men. Blood samples for determination of T, LH, FSH, 5a-dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), and oestradiol (E2) were obtained at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hours and on day 21 after implantation and then every 3 weeks until day 189, and on days 246 and 300 during follow-up. In another 36 hypogonadal men, the feasibility and side-effects of Tpellets were evaluated.

PATIENTS Fourteen patients participated in the detailed pharmacokinetic study and another 36 patients in the assessment of feasibility and side-effects. All patients (age range 18-61 years) suffered from primary or secondary hypogonadism (T < 3.6 nmol).

RESULTS The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 ± 3.7 nmol at 0.5 ± 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 ± 2.3; day 63, 34.8 ± 2.6 nmol). Thereafter serum T gradually declined and was close to baseline concentrations on day 300. Apparent terminal elimination half-life (t1⁄2) was 70.8 ± 10.7 days and apparent mean residence time 87.0 ± 45 days. On average, serum T was below 10 nmol after 180 days. Absorption of T followed a zero-order release kinetic with an absorption half-time of 74.7 days (95% confidence Interval: 71.1-78.5) and was almost complete by day 189 (95.9± 0.84%). Serum DHT and E2 were significantly elevated from day 21 to day 105 and correlated significantly with T (DHT, r = 0-65, P < 00001, EP, r = 067, P < 0.0001). SHBG was significantly decreased from day 21 to day 168. In 6 men with primary hypogonadism T suppressed LH and FSH to the eugonadal range from day 21 to 126 and 42 to 105, respectively, with nadirs occurring at day 84 (LH) and day 63 (FSH). LH and FSH were highly inversely correlated with T (r = -0.47 and -057). The only side-effect observed during 112 implantations in the total group of 50 men were 6 local infections (5.4%) leading to extrusion of 5 pellets In 3 men. When given the choice, all patients except one preferred T-pellets to their previous T medication for permanent substitution therapy.

CONCLUSION T-pellets are the androgen formulation with the longest biological action and strongest pharmacodynamic efficacy in terms of gonadotrophin suppression. The pharmacokinetic features are advantageous compared to other T preparations and the patient acceptance is high.




Pharmacokinetics

Implantation of T-pellets led to an initial short-lived burst release of testosterone within the first 2 days after application (Fig. 1, Table 2). The burst release was seen in all patients within 48 hours of implantation and accounted for much less than 1.49 ± 0.109% of the total testosterone released ((AUC 0-2/AUC)O-300) x l00), since it actually consisted only of the small peak on top of the plateau phase. A stable plateau was maintained from day 2 to 63 (day 2, 35.2 ± 2.3; day 63, 34.8± 2.6 nmol/l). Thereafter the testosterone serum levels gradually declined and were close to baseline concentrations on day 300.

Apparent terminal elimination half-life (t1⁄2) was 70.8 ± 10.7 days, and mean residence time (apparent MRT) 87.0 ± 4.45 days. Mean testosterone serum concentration was below 10 nmol/l after 180 days (Fig. 1).

T stayed above the lower normal limit (>10nmol/l) until day 246 in 2 patients, day 189 in 6, day 168 in 5, and day 147 in 1. Though not statistically significant, there was a tendency of men with larger body mass to have a lower apparent t1⁄2 and apparent MRT. The volume of distribution (VZ) showed a significant positive correlation with the body mass index (VZ = 0.83 ± 0.22 x BMI + 0.14 ± 0.02, r = 0.49, P < 0.01).

The plot of percentage testosterone absorbed vs time showed a nearly linear (zero-order) release of testosterone (Fig. 2). High linearity was demonstrated up to day 89 (r = 0.9995), with still an excellent linear regression up to day 147 (r = 0.9912). Absorption half-time was 74.7 days (95% confidence interval: 71.1-78.5) with almost complete absorption by day 189 (95.9 3 ± 0.84%). The daily release rate was 1.18 ± 0.03 mg per 200 mg pellet and the recalculated average testosterone released was 1228.95 ± 118.55 mg from the 1200 mg dose.

Fig. 1 Time course of serum testosterone concentrations (mean ± SEM) in 14 hypogonadal men. Note the burst release within the first 2 days and the plateau phase until day 63.




Discussion

This is the first study presenting detailed data on the pharmacokinetics and dynamics of T-pellets. Although T-pellets have been in clinical use for 50 years (Biskind et al ., 1990). This stability in the absorption is probably due to the mechanism of steroid absorption from the fused pellets, which is a regular erosion mechanism, depending on pellet surface area and site-specific dissolution of the crystalline steroid into the extracellular fluid (Handelsman et al., 1990).

Unlike the early T-pellets, the new T-pellets possess high stability and do not break apart after implantation, thus keeping their original shape and surface geometry. The previous higher estimate of testosterone release of 1.1 mg/ day from 100mg pellets recovered from antecubital and subscapular implantation sites may be due to site-specific absorption kinetics, possibly related to local blood flow, muscular activity, and temperature (Bishop & Folley, 1951). Furthermore, the weighing of remnants from extruded pellets could be hampered by the potential loss of material by handling. On the other hand, the calculation from percentage absorbed vs time plots assumes a constant metabolic clearance rate (MCR) for testosterone throughout the study period. In addition, individual variations of the MCR of testosterone have been reported (Meikle et al., 1988; Horton et al., 1965). Despite these disadvantages, the two methods are in good agreement.

In contrast to other testosterone preparations, T-pellets did not produce a disproportionate elevation of DHT. However, the DHT/testosterone ratio decreased owing to a larger increase of testosterone than of DHT. Nevertheless, DHT levels temporarily exceeded the upper normal limit at peak concentrations. This has also been observed for other long-acting androgen formulations (Bhasin et al., 1992; Behre & Nieschlag, 1992). Interestingly, as with testosterone microcapsules (Bhasin et al., 1992), the DHT peak occurred later than the testosterone peak. This might indicate androgen-mediated induction of 5a-reductase activity.

 

[UCFguy01]

Also how is your sleep?

My sleep is fine. Morning wood is on point too!! Sleep was good on injections too though. I only had sleep issues prior to TRT.

My only real problem on injections was libido(Like a lot of people here) and the pellets have seemed to fix that issue substantially. As I said before, I started on pellets and never had libido issues for the first 3 years of TRT while getting pellets inserted.

 

[UCFguy01]

He is only 3 weeks in!

Much more involved when it comes to libido let alone erectile function than TT, FT, estradiol, DHT, prolactin.

Hate to burst your bubble but there is an initial burst release of T (small short-lived peak) within the first 2 days (48 hrs) and levels will stay elevated off the hop as there is a plateau phase lasting roughly 60 days which is then followed by a gradual decline over the following months.


*The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 ± 3.7 nmol at 0.5 ± 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 ± 2.3; day 63, 34.8 ± 2.6 nmol). Thereafter serum T gradually declined and was close to baseline concentrations on day 300.




Summary

0BJECTIVE There are advantages and disadvantages with all of the presently available types of testosterone replacement for hypogonadal men. We performed this investigation to establish detailed data about the pharmacokinetics, pharmacodynamics, feasibility, and side-effects of subcutaneously implanted testosterone (T) pellets.

DESIGN AND MEASUREMENT In a single-dose, open-label, non-randomized study, 6 T-pellets, each containing 200mg of fused crystalline T, were Implanted in the subdermal fat tissue of the lower abdominal wall of 14 hypogonadal men. Blood samples for determination of T, LH, FSH, 5a-dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), and oestradiol (E2) were obtained at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hours and on day 21 after implantation and then every 3 weeks until day 189, and on days 246 and 300 during follow-up. In another 36 hypogonadal men, the feasibility and side-effects of Tpellets were evaluated.

PATIENTS Fourteen patients participated in the detailed pharmacokinetic study and another 36 patients in the assessment of feasibility and side-effects. All patients (age range 18-61 years) suffered from primary or secondary hypogonadism (T < 3.6 nmol).

RESULTS The pharmacokinetic study in 14 hypogonadal men revealed an initial short-lived burst release of T with a peak concentration of 49.0 ± 3.7 nmol at 0.5 ± 0.13 days which was followed by a stable plateau lasting until day 63 (day 2, 35.2 ± 2.3; day 63, 34.8 ± 2.6 nmol). Thereafter serum T gradually declined and was close to baseline concentrations on day 300. Apparent terminal elimination half-life (t1⁄2) was 70.8 ± 10.7 days and apparent mean residence time 87.0 ± 45 days. On average, serum T was below 10 nmol after 180 days. Absorption of T followed a zero-order release kinetic with an absorption half-time of 74.7 days (95% confidence Interval: 71.1-78.5) and was almost complete by day 189 (95.9± 0.84%). Serum DHT and E2 were significantly elevated from day 21 to day 105 and correlated significantly with T (DHT, r = 0-65, P < 00001, EP, r = 067, P < 0.0001). SHBG was significantly decreased from day 21 to day 168. In 6 men with primary hypogonadism T suppressed LH and FSH to the eugonadal range from day 21 to 126 and 42 to 105, respectively, with nadirs occurring at day 84 (LH) and day 63 (FSH). LH and FSH were highly inversely correlated with T (r = -0.47 and -057). The only side-effect observed during 112 implantations in the total group of 50 men were 6 local infections (5.4%) leading to extrusion of 5 pellets In 3 men. When given the choice, all patients except one preferred T-pellets to their previous T medication for permanent substitution therapy.

CONCLUSION T-pellets are the androgen formulation with the longest biological action and strongest pharmacodynamic efficacy in terms of gonadotrophin suppression. The pharmacokinetic features are advantageous compared to other T preparations and the patient acceptance is high.




Pharmacokinetics

Implantation of T-pellets led to an initial short-lived burst release of testosterone within the first 2 days after application (Fig. 1, Table 2). The burst release was seen in all patients within 48 hours of implantation and accounted for much less than 1.49 ± 0.109% of the total testosterone released ((AUC 0-2/AUC)O-300) x l00), since it actually consisted only of the small peak on top of the plateau phase. A stable plateau was maintained from day 2 to 63 (day 2, 35.2 ± 2.3; day 63, 34.8± 2.6 nmol/l). Thereafter the testosterone serum levels gradually declined and were close to baseline concentrations on day 300.

Apparent terminal elimination half-life (t1⁄2) was 70.8 ± 10.7 days, and mean residence time (apparent MRT) 87.0 ± 4.45 days. Mean testosterone serum concentration was below 10 nmol/l after 180 days (Fig. 1).

T stayed above the lower normal limit (>10nmol/l) until day 246 in 2 patients, day 189 in 6, day 168 in 5, and day 147 in 1. Though not statistically significant, there was a tendency of men with larger body mass to have a lower apparent t1⁄2 and apparent MRT. The volume of distribution (VZ) showed a significant positive correlation with the body mass index (VZ = 0.83 ± 0.22 x BMI + 0.14 ± 0.02, r = 0.49, P < 0.01).

The plot of percentage testosterone absorbed vs time showed a nearly linear (zero-order) release of testosterone (Fig. 2). High linearity was demonstrated up to day 89 (r = 0.9995), with still an excellent linear regression up to day 147 (r = 0.9912). Absorption half-time was 74.7 days (95% confidence interval: 71.1-78.5) with almost complete absorption by day 189 (95.9 3 ± 0.84%). The daily release rate was 1.18 ± 0.03 mg per 200 mg pellet and the recalculated average testosterone released was 1228.95 ± 118.55 mg from the 1200 mg dose.



View attachment 12704
Fig. 1 Time course of serum testosterone concentrations (mean ± SEM) in 14 hypogonadal men. Note the burst release within the first 2 days and the plateau phase until day 63.




Discussion

This is the first study presenting detailed data on the pharmacokinetics and dynamics of T-pellets. Although T-pellets have been in clinical use for 50 years (Biskind et al ., 1990). This stability in the absorption is probably due to the mechanism of steroid absorption from the fused pellets, which is a regular erosion mechanism, depending on pellet surface area and site-specific dissolution of the crystalline steroid into the extracellular fluid (Handelsman et al., 1990).

Unlike the early T-pellets, the new T-pellets possess high stability and do not break apart after implantation, thus keeping their original shape and surface geometry. The previous higher estimate of testosterone release of 1.1 mg/ day from 100mg pellets recovered from antecubital and subscapular implantation sites may be due to site-specific absorption kinetics, possibly related to local blood flow, muscular activity, and temperature (Bishop & Folley, 1951). Furthermore, the weighing of remnants from extruded pellets could be hampered by the potential loss of material by handling. On the other hand, the calculation from percentage absorbed vs time plots assumes a constant metabolic clearance rate (MCR) for testosterone throughout the study period. In addition, individual variations of the MCR of testosterone have been reported (Meikle et al., 1988; Horton et al., 1965). Despite these disadvantages, the two methods are in good agreement.

In contrast to other testosterone preparations, T-pellets did not produce a disproportionate elevation of DHT. However, the DHT/testosterone ratio decreased owing to a larger increase of testosterone than of DHT. Nevertheless, DHT levels temporarily exceeded the upper normal limit at peak concentrations. This has also been observed for other long-acting androgen formulations (Bhasin et al., 1992; Behre & Nieschlag, 1992). Interestingly, as with testosterone microcapsules (Bhasin et al., 1992), the DHT peak occurred later than the testosterone peak. This might indicate androgen-mediated induction of 5a-reductase activity.

That's a lot to unpack there Madman. Thanks for all of the data.

I'll keep checking in to give my updates as the weeks progress. I plan on updating once a week through the full 12 weeks to track how things go.

 

[Tman]

In the pursuit of libido only, pellets work for me soooo much better. Injections and pellets both work great for me in terms of energy, antidepressant effects, and mood......but the libido was always not very strong at all with injections on any protocol(for whatever reason). I'll take the extra few hundred dollars yearly for libido alone.

I hope it works for you... I've been chasing the proverbial tail for too long. So, I love to read about others how have found success. I can always tell the ones, for the most part who have truly found success, they tend to disappear off these forums

 

[Tman]

My sleep is fine. Morning wood is on point too!! Sleep was good on injections too though. I only had sleep issues prior to TRT.

My only real problem on injections was libido(Like a lot of people here) and the pellets have seemed to fix that issue substantially. As I said before, I started on pellets and never had libido issues for the first 3 years of TRT while getting pellets inserted.

I can relate...I have very different effects from cream and shots. Cream positively impacts my joints, general aches and pains, and libido. It also causes me to barely pee each morning, which is why I don't like to use it too often.

 

[UCFguy01]

Week 4.....

Libido is firing on all cylinders. Good sleep, energy, and mental well being.

Blood work is this Friday

 

[UCFguy01]

On a side note........

My bitcoins are going through the roof!!!!! lol

 

[joetown2001]

Week 4.....

Libido is firing on all cylinders. Good sleep, energy, and mental well being.

Blood work is this Friday

Where are you at in week 5?

 

[UCFguy01]

Feeling good in week 5. Still have the libido in tact(on fire). Good energy, good mental sense of well being. Can't complain about a thing really.

 

[UCFguy01]

It's also weird how the pellets don't raise my E2 like the injections did.

Total T: 1100
E2: 40 (used to be around 70-100 on injections without an AI)

I'm going to ask for one more pellet next time. I used to get pellets and my total T was around 1200-1400 and I really felt great. Plus the good feeling seemed to last longer.

 

[madman]

Where are you at in week 5?

I would be more concerned with the 2-3 month mark!

 

[madman]

It's also weird how the pellets don't raise my E2 like the injections did.

Total T: 1100
E2: 40 (used to be around 70-100 on injections without an AI)

I'm going to ask for one more pellet next time. I used to get pellets and my total T was around 1200-1400 and I really felt great. Plus the good feeling seemed to last longer.

post#37
Feeling good in week 5. Still have the libido in tact(on fire). Good energy, good mental sense of well being. Can't complain about a thing really.


You are only 5 weeks in and stated that you feel great yet you already want to jack your T level up further?

Regardless you are fixating on TT!

As I have stated numerous times although TT is important to know FT is what truly matters as it is the active unbound fraction of testosterone responsible for the positive effects.

You should be far more concerned with where your FT sits.

The only way to truly know is to have it tested using the most accurate assays such as the gold standard Equilibrium Dialysis or Ultrafiltration.

Keep in mind that with a TT 1100 ng/dL one can easily achieve a healthy FT level even if having higher SHBG.