Cycling TRT

[DorianGray]

I'm wondering about the validity on a clinical and perceived basis of cycling on and off TRT. I wouldn't eve pursue the question except for some research that was done on it, believe from University of Texas (Huston?). And I can't find the link now, ncbi, I thought. Study involved Test Propionate, cycling 4 weeks on 4 weeks off then a break period. Again, apologizes, I can't locate the exact study. Madman's extensive knowledge may already have it foremost.

Reason for consideration: I got on TRT thinking to boost libido when my levels were 671 TT at its lowest but relatively high SHBG and low FreeT. Got it all optimal for awhile but did nothing for libido except briefly. Went from test cyp, quite for about 1-1/2 year, tried clomiphene for 9 months, quite several months, then test cream. Each time observed "honeymoon" phases with libido. Now off cream for about two weeks and feeling better then ever.

So, what's the point? Perhaps there can be some positive physical benefit from being on TRT short term cycling. Not for libido-too many factors and unpredictable, but for maintaining bone mass, muscle and other organ benefits controlled by the hormone. In the study I mentioned, their conclusion was it had some validity.

 

[madman]

I'm wondering about the validity on a clinical and perceived basis of cycling on and off TRT. I wouldn't eve pursue the question except for some research that was done on it, believe from University of Texas (Huston?). And I can't find the link now, ncbi, I thought. Study involved Test Propionate, cycling 4 weeks on 4 weeks off then a break period. Again, apologizes, I can't locate the exact study. Madman's extensive knowledge may already have it foremost.

Reason for consideration: I got on TRT thinking to boost libido when my levels were 671 TT at its lowest but relatively high SHBG and low FreeT. Got it all optimal for awhile but did nothing for libido except briefly. Went from test cyp, quite for about 1-1/2 year, tried clomiphene for 9 months, quite several months, then test cream. Each time observed "honeymoon" phases with libido. Now off cream for about two weeks and feeling better then ever.

So, what's the point? Perhaps there can be some positive physical benefit from being on TRT short term cycling. Not for libido-too many factors and unpredictable, but for maintaining bone mass, muscle and other organ benefits controlled by the hormone. In the study I mentioned, their conclusion was it had some validity.

Sure.....if you can handle going from hypogonadal--->eugonadal let alone running supra-physiological (high/in many cases absurdly high) T levels only to end up being hypogonadal again!

Although steady-state would be reached much sooner when using TP.....pulling the plug 4 weeks in would result in crashing T levels.

Even when using the medium-acting esters (TE/TC) it will take 4-6 weeks for blood levels to stabilize.....pulling the plug 4 weeks in would still result in crashing T levels.

The body would have no clue whether it is coming or going.

To what degree one will experience negative effects during the 4 weeks off would come down to the dose used/individual.

The goal of trt is to achieve healthy hormones which will result in relief/improvement of low-t symptoms (energy/mood/libido/erectile function/recovery/body composition)/ overall well-being let alone prevent/minimize any possible side-effects and keeping blood markers healthy long-term.

Keep in mind that the study was for 20 weeks and the 24 patients were older men 70 ± 2 yr of age with 8 men following the monthly cycled testosterone (MO, n=8; alternating months of 100 mg testosterone-enanthate/week and placebo).


*Twenty-four healthy, community-dwelling older men (60 – 85 yr) with endogenous levels of serum total testosterone in the lower half of the normal range (between 280 and 500 ng/dl)




A Randomized Pilot Study of Monthly Cycled Testosterone Replacement or Continuous Testosterone Replacement Versus Placebo in Older Men (2011)

Context: Cycling androgens have been reported by athletes to improve physical performance by enhancing muscle mass and strength, a paradigm that has not been studied, and may have clinical value in older men being treated with testosterone.

Objective: We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current standard of care continuous therapy on body composition and muscle strength in older men.

Design, Setting, and Patients: Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were randomized at the Institute for Translational Sciences-Clinical Research Center into a 5-month double-blind placebo-controlled trial.

Intervention: Subjects were dosed weekly for 5 months, receiving continuous testosterone (TE, n=8; 100 mg testosterone enanthate, IM injection), monthly cycled testosterone (MO, n=8; alternating months of testosterone and placebo), or placebo (PL, n=8).

Main Outcome Measures: Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength. Secondary outcomes included body weight, serum hormones, and mixed-muscle protein fractional synthesis rate (FSR).

Results: Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO (P <0.05). Upper body muscle strength increased in TE, and lower body muscle strength increased in TE and MO (P<0.05). FSR increased in TE and MO (P< 0.05) but not in PL.

Conclusions: Cycled testosterone improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone.



The use of testosterone is increasing in middle-aged and older men in the United States (1). Testosterone is used to enhance athletic performance, with cycled dosing being a common practice among athletes (2, 3). However, the mechanisms through which cycled testosterone exert its action on skeletal muscle are poorly understood. In previous studies, the short-term (1 month) anabolic effect of testosterone is consistently associated with an increase in basal (fasting) rates of muscle protein synthesis (4 –7). However, as the duration of testosterone administration increases, the potential contributions of fasting rates of muscle protein synthesis and breakdown to the overall anabolic response is less clear (5, 8) and may involve a shift from an initial promotion of muscle protein synthesis to a later slowing of protein degradation (5). Because cycling androgens is highly successful among athletes at enhancing muscle mass and strength, we sought to determine whether a cycled testosterone administration (i.e. using half the dose) would be similarly efficacious in healthy older men, because they represent the most clinically treated age group and suffer the greatest risk of testosterone side effects.

*Therefore, we conducted a randomized, double-blinded trial in older men to test the efficacy of testosterone, administered for 5 months in a monthly cycled on-off fashion. We hypothesized that monthly cycled testosterone administration would enhance body composition and muscle strength via a preferential stimulation of muscle protein synthesis.




Serum total testosterone

All subjects entered the study with similar concentrations of circulating total testosterone in the lower half of the normal range (348 88 ng/dl). Total testosterone remained at baseline concentrations after each month of placebo treatment and increased after each month of testosterone treatment regardless of group (Fig. 1A). Among all groups, testosterone concentrations never went out of the normal upper physiological range in response to testosterone treatment (range between months 0 and 5, 157– 1303 ng/dl).


Fractional synthetic rate

Postabsorptive mixed-muscle FSR at baseline were similar between groups and remained unchanged in PL (Fig. 1B). FSR increased in both TE and MO at months 1 and remained elevated above baseline for the remainder of the study.


Lean body mass (LBM) and fat mass

LBM increased in both TE and MO after the first month of testosterone, which was sustained in TE across the 5 months (Fig. 1C).

Although LBM returned back to near baseline levels in MO around month 2 (i.e. between the first cycle of placebo and the second cycle of testosterone), the subsequent months showed a sustained increase in LBM.

*The decline in fat mass was significant only in TE (Fig. 1D).


Muscle strength

Muscle strength for arm curl (Fig. 1E), arm extension (Fig. 1F), leg curl (Fig. 1G), and leg extension (Fig. 1H) increased in TE.

Leg curl strength increased in MO, and there was a trend for increased leg extension (P 0.076). There were no changes in one-repetition maximal voluntary strength tests in PL.




Discussion

Cycling of androgens has long been employed by athletes to build muscle strength and mass and improve performance without careful scientific study (2, 3). This study determined 1) the efficacy of cycled testosterone to increase muscle mass and strength in older men and 2) whether cycled testosterone promotes skeletal muscle anabolism by preferential stimulation of muscle protein synthesis. We found that monthly cycles of testosterone preferentially stimulated muscle protein synthesis, likely due to the repeated removal and reintroduction of the anabolic stimulus testosterone. The rationale for conducting this study came from our previous work in older men where we showed that skeletal muscle protein synthesis accounted for the anabolic effects of testosterone at 1 month, but at 6 months, net anabolism resulted from an inhibition of skeletal muscle breakdown (5, 15).

Our healthy older men provided a unique model to study cycling testosterone because their total testosterone concentrations were in the lower half of the normal range and increased to the upper half of the normal range with cycled testosterone administration, therefore enabling us to assess the mechanism by which testosterone promotes muscle anabolism by increasing testosterone while still maintaining serum values within the normal range for men.

Interestingly, Fig. 1A shows that older men in the MO group returned to baseline testosterone serum concentrations during the off months without testosterone. Although LBM declined somewhat during the initial month without testosterone, it recovered with the subsequent month of replacement and did not decline during the subsequent month without testosterone, staying nearly identical to the TE group at month 5 (Fig. 1C). More importantly, skeletal muscle protein synthesis remained elevated during the cycled withdrawing of testosterone (Fig. 1B). The change in total fat mass followed a similar inverse pattern to LBM (Fig. 1D) and contributed to the significant decline in percent fat mass in both groups receiving testosterone. Although changes in muscle strength in MO reached significance only in a single muscle group, strong positive trends were seen in all other muscle groups (Fig. 1, E–H).

Our findings of decreased high-density lipoprotein (HDL) cholesterol in TE and MO are consistent with the observed decreases in HDL cholesterol after testosterone treatment in healthy older men by others (16). It is not clear why triglycerides decreased only in the TE group, but it is possible that, although not significant, the lower triglyceride concentrations in this group at baseline indicate some predisposition in this group for a further decline in circulating lipids. Because previous studies have shown that testosterone side effects increase with increasing doses, it is possible to infer that a therapeutic approach using half the testosterone dose would result in reduced side effects (17, 18).

With respect to efficacy and mechanism, the major difference in the two treatment paradigms appears to be a slowing of the gains in lean mass and strength in MO relative to TE during the initial months of treatment. Importantly, however, by 5 months, gains in lean mass were similar in MO and TE, and gains in strength in MO approached or equaled those of TE. Notably, the month-to-month variation in LBM in the MO group was much greater than that of FSR, which remained relatively constant once treatment was initiated during month 1. This suggests that testosterone’s anabolic effects are not entirely explained by changes in fasting muscle protein synthesis but may also involve changes in fasting rates of muscle protein breakdown or fed-state muscle protein metabolism and, furthermore, that changes in these variables are responsible for the relatively slower rate of adaptation to the MO dosing regimen.

Finally, our data show that by raising testosterone concentrations from the lower half to the upper half of the normal range in a monthly cycled paradigm, skeletal muscle FSR remains consistently elevated in healthy older men. Thus, if monthly on/off cycles of testosterone can consistently increase muscle protein synthesis and LBM without an increase in side effects, then this paradigm offers significant treatment for preventing sarcopenia in older men. However, larger and longer-term studies are needed to assess the cumulative effects of this dosing paradigm on efficacy, safety, and functions of daily living such as sexual function, vitality, and overall quality of life.

 

[madman]

Highly doubtful such protocol would have a positive impact on energy/mood/libido/erectile function let alone maintaining overall health long-term!

*However, larger and longer-term studies are needed to assess the cumulative effects of this dosing paradigm on efficacy, safety, and functions of daily living such as sexual function, vitality, and overall quality of life.

 

[madman]

Unfortunately, this long-term study (52 weeks) never had a fighting chance.....0 participants!

ClinicalTrials.gov

clinicaltrials.gov

Recruitment Status: Withdrawn (Unable to identify any qualifying subjects willing to enroll in this study.)

First Posted: August 16, 2011

Last Update Posted: October 2, 2015



Brief Summary:

The general hypothesis is that administration of testosterone to healthy, older men for 52 weeks (1 year) following a cycle of 4 weeks of testosterone administration and 4 weeks without testosterone (i.e., monthly cycled regimen) will provide the same gains in muscle strength, muscle mass, and bone density as the standard of care (SOC), continuous administration of testosterone for 52 weeks.


Detailed Description:

The hypothesis is based on data from our current NIA-funded R01 protocol. The investigators treated older men with weekly intramuscular injections of testosterone enanthate (100 mg) for 4 weeks followed by 4 weeks of placebo injections. This 4-week-on, 4-week-off cycled treatment regimen was repeated for 5 cycles (20 weeks). This group was compared with a group of older men who received SOC weekly intramuscular injections of testosterone enanthate (100 mg) for 20 weeks and another group who received placebo injections. Our preliminary data showed equal gains over placebo in muscle strength and lean body mass in those who received testosterone for 20 weeks, whether SOC continuous or cycled. Moreover, both groups showed greater bone density and markers of bone formation over placebo. In terms of the anabolic actions of testosterone on skeletal muscle in older men, the investigators found that continuous and cycled administration of testosterone primarily stimulated muscle protein synthesis for the 20 weeks of the study. Cycled testosterone administration enhanced muscle protein synthesis throughout the full 5 cycles of 20 weeks, with no significant loss in muscle protein synthesis during the off-cycle weeks. Additionally, cycled and continuous testosterone administration reduced serum markers of bone resorption compared with placebo. These exciting findings of the benefits of a cycled testosterone regimen in older men represent a novel therapeutic paradigm over the existing SOC approach of continuous administration. The investigators believe the cycled regimen offers a more safe and efficacious approach to combat sarcopenia and osteoporosis with equal anabolic benefit to muscle and bone with only half the dose of testosterone. Critical to the application of this significant paradigm shift in testosterone administration is to determine whether these effects at 20 weeks can persist for the 52 weeks proposed in this study, which represents a treatment duration applicable to the traditional SOC approach.




Primary Outcome Measures:

1. Muscle Strength [ Time Frame: 1 year ]
   Muscle strength will be measured using a Biodex 4. All strength measures will be normalized by dividing absolute strength by lean muscle mass.
2. Lean Body Mass and Muscle Volume [ Time Frame: 1 year ]
   Lean body mass will be determined by DEXA and muscle volume by MRI.
3. Bone density [ Time Frame: 1 year ]
   Bone density will be determined by DEXA.

Secondary Outcome Measures:

1. Assessment of risk factors [ Time Frame: 1 year ]
   Prostate health Complete Blood Count (CBC)/hypertension Serum estradiol Bone fracture risk.
2. Assessment of Physical Performance [ Time Frame: 1 year ]
   Subjects will complete a timed 400 Molecular Weight (400MWT) at each study session to assess changes in gait speed as a proxy for physical function. In addition, subjects will complete Patient-Reported Outcomes Information System (PROMIS®) Short Forms addressing questions related to general health, fatigue, and physical functioning
3. Assessment of muscle signaling [ Time Frame: 1 year ]
   Testosterone can alter skeletal muscle cell signaling. We will measure changes in key signaling proteins in skeletal muscle tissue. We anticipate that testosterone treatment will increase levels of anabolic signaling proteins and suppress levels of catabolic signaling proteins
4. Assessment of bone metabolism. [ Time Frame: 1 year ]
   Testosterone can decrease rates of bone turnover (net increase of bone formation). We will measure changes in serum markers of bone formation and bone resorption.
5. Assessment of Inflammation [ Time Frame: 1 year ]
   Testosterone is protective against inflammation. We will measure concentrations of cytokines in blood and muscle tissue.
6. Assessment of cardiac stiffness [ Time Frame: 1 year ]
   Cardiac stiffness and relaxation will be assessed using echocardiography.

 

[DorianGray]

Yes, that was it. I guess I can't find any hope in that study! Jeez, piss poor recruitment for the longer term research proposal. I could have been N=1. And again, thanks Madman for posting info that reminds us we should place stock in sound data rather than flopping about with trial and error or anecdotal evidence.

 

[ivkonst2017]

The only thing this can cause is stress for the body and mind. Totally couterproductive idea

 

[Willyt]

Study would have been more interesting had it used shorter half life propionate rather enanthate.

On related note, I have been experimenting with taking 1-2 days off each week from low dose daily propionate protocol under the premise that it may be helpful to challenge your HPTA by periodically returning to baseline levels. (It's essentially what Natesto is doing on a daily basis). I'll report back with observations next month.

 

[madman]

Study would have been more interesting had it used shorter half life propionate rather enanthate.

On related note, I have been experimenting with taking 1-2 days off each week from low dose daily propionate protocol under the premise that it may be helpful to challenge your HPTA by periodically returning to baseline levels. (It's essentially what Natesto is doing on a daily basis). I'll report back with observations next month.

Study would have been more interesting had it used shorter half life propionate rather enanthate.

What would it matter you would be crashing your T levels every 4 weeks!


On related note, I have been experimenting with taking 1-2 days off each week from low dose daily propionate protocol under the premise that it may be helpful to challenge your HPTA by periodically returning to baseline levels. (It's essentially what Natesto is doing on a daily basis). I'll report back with observations next month.

Not going to make a shit lick of a difference your T levels are steady-state most of the week.

When it comes to half-life prop and Natesto are 2 different animals.

Natesto has the advantage of short-lived peaks/long trough time (2-3 times)/24 hrs.

Daily prop could never mimic such!

 

[Willyt]

Madman you are underestimating the speed at which Prop clears the system versus medium esters. You are most definitely not at a steady state if using daily Prop injections.

A Prop study would indeed have looked very different versus Enanthate, which takes too long to build up and dissipate during the "off" month.

I have used Natesto quite a bit and yes its a different animal. But based on my experience, I would say daily Prop feels much closer to Natesto than to Cypionate or Enanthate.

 

[madman]

Madman you are underestimating the speed at which Prop clears the system versus medium esters. You are most definitely not at a steady state if using daily Prop injections.

A Prop study would indeed have looked very different versus Enanthate, which takes too long to build up and dissipate during the "off" month.

I have used Natesto quite a bit and yes its a different animal. But based on my experience, I would say daily Prop feels much closer to Natesto than to Cypionate or Enanthate.

Again when it comes to the half-life of unesterified T (10-100min) and esterified T (enanthate/cypionate) let alone short-acting prop.....a big difference to say the least.

Your HPG axis will be shut down on a daily prop protocol even if you take a day or two off each week as the recovery of the HPG axis will not happen!

Natesto Tmax (approx.40min) let alone when dosed 2-3X daily will result in minimal suppression of the HPG axis due to Natestos short-lived peaks/long trough time.


*The 24-hour pharmacokinetic profile of testosterone for patients on TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur on average every 2 hours. A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h). The nadir (trough) between doses correlates well with pre-treatment endogenous levels at diagnosis.

*The unique, pulsatile, pharmacokinetic profile is believed to have limited impact on the HPG axis with significant trough time preserving luteinizing hormone (LH), follicle-stimulating hormone (FSH), endogenous testosterone production, and sperm counts, while also limiting excess RBC production, estradiol, DHT and PSA in clinical trials.


The key point here.....SIGNIFICANT TROUGH TIME in 24hr period.

The daily prop protocol could never achieve let alone mimic such due to its longer half-life!




post #68/70

Tips on how to blend propionate with enanthate (or cypionate)?

@Cataceous, as you know, I am interested in following your logic. I am currently not on either ester. I was planning on starting both esters simultaneously. As I read your post above, however, it sounds like you did this one ester at a time until you started the blend. Was this by design or were...

www.excelmale.com

 

[madman]

Madman you are underestimating the speed at which Prop clears the system versus medium esters. You are most definitely not at a steady state if using daily Prop injections.

A Prop study would indeed have looked very different versus Enanthate, which takes too long to build up and dissipate during the "off" month.

I have used Natesto quite a bit and yes its a different animal. But based on my experience, I would say daily Prop feels much closer to Natesto than to Cypionate or Enanthate.

Cycling testosterone/AAS for the sole purpose of muscle/strength enhancement.....sure.

For replacement of T due to hypogonadism/TDS.....not a chance!

Even if the study used TP.....4 weeks on/off would be idiotic as you will still crash and be hypogonadal.

Daily prop similar to daily Natesto.....PIPE DREAM!

 

[madman]

Natesto: A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h).

TP: if anything maximal peak T would be 4-6 hrs (Tmax) post-injection (definitely not a short-lived peak) and most likely longer depending on the dose used let alone it will take much longer to hit a true trough.


Get back to me when you can have labs done hourly to see where your true peak/trough (24 hrs) truly sits.....LOL!

 

[ivkonst2017]

Cycling testosterone/AAS for the sole purpose of muscle/strength enhancement.....sure.

For replacement of T due to hypogonadism/TDS.....not a chance!

Even if the study used TP.....4 weeks on/off would be idiotic as you will still crash and be hypogonadal.

Daily prop similar to daily Natesto.....PIPE DREAM!

Totally agree and beyound that, even if there was a way to be not fully shut down...why the hell to put the body through this stress and roller coaster?

 

[DorianGray]

Totally agree and beyound that, even if there was a way to be not fully shut down...why the hell to put the body through this stress and roller coaster?

In other words, if one is not significantly hypogonadal, why bother with anything other than Natesto?

 

[ivkonst2017]

In other words, if one is not significantly hypogonadal, why bother with anything other than Natesto?

No, you misunderstood me. I said being shut down is not so important and people are too obsessed with that. I started TRT with almost 600 ng/dl total t and since I feel way better I couldnt care less Im shut down on injections

For me using natesto is totally justified if someone feels better on it in relation to injections and only because of that

 

[Cataceous]

.... I said being shut down is not so important and people are too obsessed with that. I started TRT with almost 600 ng/dl total t and since I feel way better I couldnt care less Im shut down on injections
...

You are of course entitled to your opinion, but the absence of obvious side effects now doesn't preclude the possibility of neurological deficits later in life from chronic GnRH deprivation. I'm not saying this is very likely, but it is still an unknown, and GnRH is just one of many hormones affected negatively by HPTA shutdown.

My anecdote is that restoration of GnRH coincided with a significant improvement in cognition.

 

[ivkonst2017]

You are of course entitled to your opinion, but the absence of obvious side effects now doesn't preclude the possibility of neurological deficits later in life from chronic GnRH deprivation. I'm not saying this is very likely, but it is still an unknown, and GnRH is just one of many hormones affected negatively by HPTA shutdown.

My anecdote is that restoration of GnRH coincided with a significant improvement in cognition.

At the end we dont know what side effects may occur on our health no matter what we do or dont. But yes I advocate being decisive when the possible benefits to possible negatives have been compared and analyzed.

I've started TRT as an optimization, not as a treatment to a severe deficiency. At some point people can also use HCG, DHEA or Pregnenolone to mitigate most possible side effects to being shut down

The same way I'm about to start thyroid replacement next week. My thyroid is not terrible or outside range, but the analysis of it and the symptoms show a treatment can be beneficial. For me this is enough to support a replacement intervention.

 

[ivkonst2017]

My anecdote is that restoration of GnRH coincided with a significant improvement in cognition.

In what context is that? Will a man with low t symptoms no matter the test levels and his natural production online have a better cognition in relation to a shut down man with optimised testosterone in most cases? Which of the two is more likely to have a better cognitive performance?

 

[Cataceous]

...
I've started TRT as an optimization, not as a treatment to a severe deficiency. ...

... I started TRT with almost 600 ng/dl total t and since I feel way better I couldnt care less Im shut down on injections
...

This is precisely why Natesto is interesting. You get to sample higher testosterone levels without breaking a functioning HPTA.

In what context is that? Will a man with low t symptoms no matter the test levels and his natural production online have a better cognition in relation to a shut down man with optimised testosterone in most cases? Which of the two is more likely to have a better cognitive performance?

What is "optimized testosterone"? It seems as though lately guys are wanting to define this as the highest amount that doesn't cause overt side effects. I've argued that nature already decided on optimum levels—which are found in the averages for healthy young men. These are the levels that lead to the best reproductive success, which arguably correlates well with measures of overall success in life. Yes, average levels are a compromise. Maybe you sacrifice on some traits, like athleticism, but you gain on others, like the ability to maintain a stable relationship. "... men with higher basal T levels are less likely to marry and more likely to divorce..."1

In any case, the context for my anecdote is this precedence, which is also my treatment progression:

hypogonadism < TRT < TRT+hCG < TRT+GnRH+...​

In short, the better I reproduce a normal HPTA, the better I feel. This is in part why I've become a proponent of preserving the HPTA when possible. The theoretical issues also figure in this: For example, all those GnRH and LH receptors with as-yet unknown functions.

 

[ivkonst2017]

What is "optimized testosterone"? It seems as though lately guys are wanting to define this as the highest amount that doesn't cause overt side effects. I've argued that nature already decided on optimum levels—which are found in the averages for healthy young men.

The healthy young man with good testosterone are very rare today. On another point I dont agree with you is that levels on TRT cannot be compared to endogenous levels, on replacement usually we need to go higher to achieve the same effect. Same seems to be with thyroid for FT3 levels.

So very often if a guy at 18 feels perfect at 1000 ng/dl(lets assume SHBG is always the same for simplicity of the example) and he screws up his health somehow, on replacementt he may need to go to 1300 to get the same effect. Should he be concerned that 1300 is above the reference range if he feels good with no side effects? I definetely dont think so.

I would define optimal testosterone as the highest safe levels giving best benefits and NO side effrcts and health risk. Another way to put it - a total body health approach(not just testosterone) with the aim of maximum improvement of quality of life without compromising health.

By benefits I mean mostly resolution of mental/emotional/energy/sexaul symptoms and I totally dont advocate going higher for the sake of any fitness gains.

Recently I had a great discussion with my doctor, he also is not advocating minimal effective dosage but maximum safe optimal dosage instead. I tried to challenge him on that although I agree with him and it was interesting discussion