Trt faq & discussion goes here

[Serotonin101]

5. This is not a forum for TRT or medical advice, although we will allow discussion under the pretence that bluelight is not responsible for any outcomes based on advice given. We will try our best to help although in most cases, your doctor is best dealing with your issue.
----Steroid Discussion Rules---

This is not a trt forum. As a barrage of trt related questions are cropping up and I'm tired of repeating the same thing over and over I'll try to answer the frequently asked ones here now. Anything not covered can be asked here. If you are on trt and wish to blast and cruise then you can start your own threads pertaining to your circumstances.

Test gel questions
-gel is a shitty medium for testosterone. It gives irregular release rates, causes increased aromatase and 5a reductase action, and you risk spreading the gel to others. Get on injectable test either by your doctor or self prescribed. Testosterone enanthate or cypionate or sustanon are best.

Oral testosterone replacement
-test has shitty oral bioavailability of maybe 10%. Irregular absorption rates due to stomach contents (requires high fat food consumed with dose to even be considered) and is a waste of money. Get on injectable test.

Hcg questions
-hcg is for fertility reasons ONLY. It mimics leutenizing hormone in males thus desensitizing leydig cells further causing increased hpta suppression. No ifs ands or buts. Do not use unless trying to conceive.

Serm questions
Serms are not needed if you are only doing trt. If you start having gyno issues dose 20mg tamoxifen citrate daily until gyno symptoms subside while increasing AI dosage and see next point.

Aromatase inhibitor & estrogen questions
-AIs are typically prescribed for TRT generally arimidex aka anastrozole. Common practice is 0.5mg arimidex taken on injection days if twice weekly shots or 1mg if once weekly. This helps prevent some of your test from turning into estrogen which causes problems. If you start getting gyno then increase your AI dose, begin taking tamoxifen citrate at 20mg/day and try to lose some fat as that is more than likely your cause as fat tissue contains aromatase. Less fat=less aromatase=less estrogen.
Estrogen levels should be kept within range when on trt. If you decide to go above trt then keep your test-estradiol ratio at 50:1, ex: 1000 test : 20 e2 (estradiol).

Test dose questions
-aim to get your free test in the high normal or just below it, so 800-1200 range generally. You can guess your free test numbers by multiplying your WEEKLY test dose (in mg) by 4.5.

Injection frequency questions
- testosterone should be injected MINIMUM ONCE A WEEK if prescribed enanthate, cypionate, or sustanon. Twice weekly is preferred to keep blood levels more stable which minimizes side effects. You have two glutes, use them.

These are the frequently asked questions I see around here regarding trt. This should prevent so many threads in the future from cropping up that AREN'T THE FOCUS OF THIS FORUM . Our members have been more than courteous in answering your questions without telling 90% of you to UTFSE (use the freaking search engine) as the majority have been asked and answered numerous times. More will be added to this if more frequent questions keep arising or if mods feel something has been left out.

If something was not covered then this is the place to ask. Feel free to discuss what is working for you as well. This thread is intended to minimize clutter with otherwise excessive trt talk and repetitive questions. And ultimately: WE ARE NOT DOCTORS. CONSULT YOUR PHYSICIAN WITH SPECIFIC QUESTIONS
~Sero

 

[Genetic Freak]

A big thanks for that Serotonin...

One thing I might add, on a TRT dose it is highly unlikely for you to experience estrogen related side effects, you may in the initial stages of your TRT as your body gets used to a higher levels of testosterone after being low for so long, but it shouldn't last....

An AI could help but used sparingly, as your body is trying to adjust, personally I wouldn't bother and just allow your body to do the rest...

Remember you need estrogen for normal healthy functions, it is not your enemy.. Your bones would be fucked without estrogen, and skeletal muscle growth could be compromised...!!

 

[alan2102]

This is not a trt forum.

OK. I'll try not to turn it into one. But I do have a few comments/questions.

Test gel questions
-gel is a shitty medium for testosterone. It gives irregular release rates, causes increased aromatase and 5a reductase action, and you risk spreading the gel to others. Get on injectable test either by your doctor or self prescribed. Testosterone enanthate or cypionate or sustanon are best.
Oral testosterone replacement
-test has shitty oral bioavailability of maybe 10%. Irregular absorption rates due to stomach contents (requires high fat food consumed with dose to even be considered) and is a waste of money. Get on injectable test.

"Injectable is superior" has been my conclusion for some time. However, just a few days ago I ran into this:

https://www.ncbi.nlm.nih.gov/pubmed/10893588
J Urol. 2000 Aug;164(2):371-5.
Testosterone supplementation for erectile dysfunction: results of a meta-analysis.

... which found that transdermal was significantly more effective than either injectable or oral, and that injectable and oral were of equivalent efficacy (!). One question I have is: oral WHAT? i.e. which compound did they give orally? I'll have to get the full text to find out. Meanwhile, an interesting finding wrt transdermal.

PS: I've found other and older literature suggesting that testosterone has rather more oral bioavailability than we usually suppose. First-pass metabolism appears to be not as efficient as commonly thought. It DOES grab and destroy some, but by no means all.

hcg is for fertility reasons ONLY. It mimics leutenizing hormone in males thus desensitizing leydig cells further causing increased hpta suppression. No ifs ands or buts. Do not use unless trying to conceive.

Why would it cause desensitization at modest, physiologic doses? (i.e. any more desensitization than that of LH itself)

Whatever hpta suppression actually occurs would be a reflection of the success of HCG therapy in raising T levels.

Regarding use of HCG, consider:

1. It is said, and it makes sense, that HCG promotes synthesis of hormones/precursors upstream of T -- such as pregnenolone, progesterone, and DHEA -- whereas naked T supplementation might tend to depress same.

2. HCG maintains testicular volume. Associated with this must be increased biochemical/metabolic activity; HCG must maintain testicular physiology as well as morphology. This seems to me a good thing. Keep the nuts "alive", so to say, versus the deadening (shut-down) effect of naked T supplementation. Use it or lose it.

3. Use of HCG as a TRT-alternative seems to be picking up some steam; see:

http://www.tandfonline.com/doi/full/10.3109/13685538.2015.1092021#abstract
Aging Male 2015
Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone

https://www.ncbi.nlm.nih.gov/pubmed/26485362
Horm Metab Res. 2016
The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism.

Also, herewith a commentary from an HCG-for-TRT advocate (interesting):

http://www.mombu.com/medicine/t-a-p...-depression-nail-testicular-down-2307457.html
A Primer on HCG and Dr. Shippen's HCG Protocol

Estrogen levels should be kept within range when on trt. If you decide to go above trt then keep your test-estradiol ratio at 50:1, ex: 1000 test : 20 e2 (estradiol).

I would like to read some more about the test:estradiol ratio. Do you have any links or suggestions?

Test dose questions
-aim to get your free test in the high normal or just below it, so 800-1200 range generally. You can guess your free test numbers by multiplying your WEEKLY test dose (in mg) by 4.5.

I assume when you speak of "800-1200 range" you are talking about TOTAL test, not free.

testosterone should be injected MINIMUM ONCE A WEEK if prescribed enanthate, cypionate, or sustanon. Twice weekly is preferred to keep blood levels more stable which minimizes side effects. You have two glutes, use them.

... or, why not do subcutaneous? Easier, less painful, and from what I gather equally effective. A daily sub-q injection is no big deal.

 

[CFC]

This is an old thread, and Sero hasn't been around for a while. However I'll answer some of your questions.

Regarding the study showing transdermal to be more effective, it probably doesn't show that at all, although you'd need to read it to fully understand why. Poor injection methodology likely plays a role. I'll reproduce the entire discussion from that study for you here. I've highlighted the most relevant paragraph, but the rest is worth reading:

DISCUSSION

Because of the common practice of measuring androgen when evaluating erectile dysfunction, androgen replacement therapy has proliferated. To our knowledge a causal relationship between altered levels of androgens and erectile dysfunction is not firmly established. In fact, there are few studies of androgen replacement and its effect on erectile dysfunction. In the Massachusetts male aging study testosterone was not although serum dehydroepiandrosterone was associated with patient reported erectile dysfunction. 26 It is believed that erection is achieved by synergistic reflexogenic and psychogenic mechanisms. The reflexogenic component involves sensory stimulation of the genitalia, which subsequently results in a spinal cord reflex erectile response and is largely androgen independent. The psychogenic component involves higher brain functions and depends on free testosterone. 25 Erectile dysfunction may be a consequence of a derangement in any vascular, neurological, psychogenic or endocrinological aspect of the erectile mechanism. What is relatively clear from the literature is that testosterone replacement is important in only a small subset of patients, comprising less than 5% of those with erectile dysfunction. 7

We compiled data from the literature in an attempt to create a basis for stimulating future investigation and provide insight into the rational use of androgen replacement for erectile dysfunction. From this meta-analysis of the usefulness of androgen replacement therapy for erectile dysfunction we noted that the response rate for primary etiologies was significantly higher than that for secondary etiologies, transdermal testosterone therapy was more effective than intramuscular or oral treatment, and intramuscular and oral methods of delivery were equivalent. In addition, there was a statistically significant difference in favor of testosterone over placebo, supporting a role for supplementation in select groups.

Why the response rate differs significantly in primary and secondary etiologies must be answered. A possible explanation is that men with primary testicular failure have a clearer causality of erectile dysfunction, including fewer confounding co-morbidities that would hamper a response to androgen supplementation. Those with secondary testicular failure may have associated problems, and so vascular, neurological, psychogenic and endocrinological aspects of erectile response may make it difficult ro establish a clear association with androgen deficiency. Also, better controlled studies with well developed inclusion and exclusion criteria are possible in men with primary testicular failure, providing less potential for selection bias.

One must also wonder why transdermal replacement induces a significantly better response than intramuscular or oral supplementation. The more physiological delivery pattern of the daily transdermal methods is an obvious consideration, and yet to our knowledge a mechanistic explanation is not forthcoming. It is possible that the improved response is due more to the nature of current investigation with better inclusion and/or exclusion criteria rather than to some intrinsic factor in the androgen level or rate of systemic decay. Transdermal studies are smaller than intramuscular studies (42 versus 238 cases), making direct comparison in this setting prone to error. The high response rate in the topical groups is questionable when considering the complex nature of erectile dysfunction, implying a potential bias in patient selection. A clinical trial comparing the response rates of transdermal and intramuscular routes is needed to address this issue.

A surprising finding was the similar response rate for intramuscular versus oral androgen therapy. This finding may reflect poor study design or selection bias in the treatment groups as well as poor overall response potential in these patients. The trend in differences in the scrotal versus nonscrotal application of transdermal delivery is a marginal finding that warrants crossover or comparison studies.

When considering placebo controlled crossover studies, several factors were noted. There is a surprising deficiency of well controlled studies. Because of the small number of these series, we did not use the more common Mantel-Haenszel analysis. In addition, we made no attempt to calculate a potential publication bias because of the few controlled investigations available for review. However, in our analysis we weighed each study by sample size. Ideally we would have preferred to know the placebo and testosterone response in each patient but this information was not provided. Thus, one must treat the samples as independent comparisons rather than as matched samples. Despite these difficulties we noted a statistically significant difference in favor of testosterone treatment over placebo, supporting a role for testosterone supplementation in select groups.

Controlled trials have been considered the gold standard for evaluating medical intervention. For most medical questions it has been possible to perform relatively small trials. 27 Meta-analysis has become the cornerstone of evaluating multiple, disparate clinical series in an attempt to provide information to assist physicians in clinical decision making. To avoid inherent flaws in performing this type of analysis it is important to choose a balanced group of trials for analysis. Experimental design must be similar, and inclusion criterion and outcomes comparable. In our meta-analysis we made every attempt to exclude articles that did not meet our aforementioned inclusion criteria. The systematic approach to identifying and abstracting research reports was the core of our project. Our identification of more than 17,000 reports of erectile dysfunction and/or androgen replacement with selection down to only 73 testifies to our rigorous inclusion criteria. A disappointing finding was that only 16 of these 73 reports were detailed enough for reliable data extraction, while only 11 of 16 provided details on etiology.

A potential critique of our analysis involves the inclusion criteria with regard to patient response. We included studies with a clear and quantifiable measure of erectile response with androgen supplementation, such as clinical improvement in potency, increased scores on sexual function surveys and diary entries of the number of erections. Each of these 3 measures is parallel and similar but not as good as those in more recent investigations of erectile dysfunction, such as combined penile tumescence monitoring, validated questionnaires and patient-partner diaries. 28 and 29 Given the diverse measures of response in the evaluated articles some variability was expected in results. Another potential critique of our efforts is the exclusion of nonpublished trials or the so-called publication bias. Because zero effect studies have a smaller chance of publication than statistically significant studies, there may be an increased risk of type I error. To estimate the significance of this phenomenon the theoretical number of unpublished studies with zero effect was included to change a significant into a nonsignificant result. Again, because of the small number of published series in this category, we omitted this step.

Androgen is necessary but not essential for normal libido and to our knowledge its exact role in erectile function remains unclear. When treated with visual or sexual stimuli, individuals with a castrate level of testosterone may achieve erections thought to be comparable to those in men with normal testosterone. 8 The clinical manifestations of androgen deficiency depend on the stage of sexual development in which they occur. In older males decreased virility and a catabolic effect are more predominant. In adult and aging males testosterone is needed to maintain virilization, libido, potency, secondary sexual characteristics, and muscle and bone mass. Although testosterone replacement seems reasonable in testosterone deficient men, to our knowledge supplementation has not yet been properly evaluated. Ideally androgen replacement therapy should reestablish a normal endocrine milieu that restores all androgen dependent physiological functions.

The methods of androgen replacement currently available for human use include parenteral preparations of the long acting esters of testosterone, enanthate and cypionate, oral preparations of 17α-alkylated derivatives and recently introduced transdermal preparations. The long acting 17β-hydroxy esters of testosterone, enanthate and cypionate are least costly but the efficacy and efficient use of health care expenditure in regard to these preparations are not universally accepted. Administering a 200 to 300 mg. dose every 2 to 3 weeks provides a practical option but it is far from an ideal physiological replacement. We made no attempt to standardize the frequency of administration or the dose since these factors varied among reports. In addition, the exact formulation of replacement therapy also varied. These variations may be viewed as a weakness of our review.

Oral androgen preparations have the potential for serious hepatotoxicity. However, in the rare patient who cannot receive androgen parenterally 25 or 50 mg. methyl testosterone, or 5 to 10 mg. fluoxymesterone may be given orally daily if hepatic function is closely monitored. The transdermal delivery of testosterone is convenient and reliable, and it better mimics physiological testosterone secretion. With such patches normal serum testosterone may be achieved in most men with hypogonadism. After applying the patch on the scrotal skin serum the testosterone level rapidly increases to the normal range, peaking between 2 and 6 hours after application. Because there is a gradual decrease into the hypogonadal range within 24 hours, the patch must be applied to the skin daily. When the patch is applied in the early morning, the diurnal testosterone rhythm may be closely mimicked. To our knowledge what has not been demonstrated is whether replicating this diurnal rhythm provides any physiological advantage.

An intriguing question raised by our study is the issue of appropriate first versus second line treatment of androgen related erectile dysfunction. We attempted to estimate the cost difference to address this issue. If testosterone cypionate were used as first line therapy, the estimated cost would be $68,057.75 for treating 100 patients for 6 months and then changing those in whom intramuscular therapy failed to transdermal treatment for the next 6 months (table 7). This cost assumes a 50% response rate for the initial 6 months on intramuscular therapy and an 80% rate for the next 6 months on transdermal therapy. Thus, theoretically 90 of 100 patients would respond during 1 year of treatment. This cost compares favorably to that of transdermal therapy as first line treatment at an initial yearly cost of $130,852.50 for a response in 80 of 100 patients in 1 year. The comparison does not include the cost of administering the injection, that is an office visit for some patients, home nurse visit or self-injection. Also, this comparison assumes that men refractory to intramuscular treatment would respond to transdermal therapy and there would be no inflation during treatment phase 2 when changing from intramuscular to transdermal delivery. One wonders whether the lower cost associated with parenteral testosterone as first line therapy for replacement would be offset by the marginal cost of its expected increased failure rate, increased physician time and expense as well as patient frustration with treatment failure. 30 Marginal costs are the key to understanding the role and influence of subsequent failure and necessary additional maneuvers in erectile dysfunction treatment. A marginal cost analysis of the various treatment sequence scenarios is an obvious need resulting from our report.

Regarding the ability of hCG to maintain or increase testicular volume, unfortunately that doesn't necessarily translate to a concomitant recovery in testosterone levels or long-term recovery, as this study makes clear:

https://www.ncbi.nlm.nih.gov/pubmed/23278834

(you can read a summary of it for free >>here<<. Incidentally, you may find that forum useful with regards to TRT treatment discussion).


As well as considering hCG for TRT purposes, you may also be interested in reading about the use of SERMs such as clomiphene if you haven't already, and also sometimes injections of triptorelin have been shown to 'kickstart' a recovery of the HPTA, particularly when the problem seems to be emanating from the pituitary/hypothalamus. Unfortunately no method has been shown to be universally successful, you need to figure out what works for you, so keep an open mind.

 

[alan2102]

Regarding the study showing transdermal to be more effective, it probably doesn't show that at all, although you'd need to read it to fully understand why. Poor injection methodology likely plays a role. I'll reproduce the entire discussion from that study for you here. I've highlighted the most relevant paragraph, but the rest is worth reading:

Thanks for doing the work of digging out the full text for me! Yes, interesting.

What "poor injection methodology" do you perceive?

Regarding the ability of hCG to maintain or increase testicular volume, unfortunately that doesn't necessarily translate to a concomitant recovery in testosterone levels or long-term recovery

It translates to at least SOME recovery in T levels; whether or not adequate in a given case is another question. My understanding so far is that modest hCG supplementation generally raises peak T by 100-300 ng/dL. That may or may not be sufficient; probably won't be in most cases.

Thanks for the links. It is surprising that that huge dose of hCG had such a small effect on T in those men. The abstract says that T was raised by hCG, but the figures indicate that the effect was negligible; i.e. the abstract is misleading. The article says that these men were secondary, but the numbers suggest that they were treating a bunch of primaries with burned-out nads.

I think Shippen is on the right track using hCG diagnostically to determine primary v. secondary (and degree of primary- versus secondary-ness; some cases will be a mix). I'm much less convinced about hCG monotherapy. For secondaries, hCG can make a contribution, but most men will require a multi-modal approach -- a stack -- if they are not going to go with TRT itself. For primaries, TRT is obviously the only option.

Here's an interesting one, showing modest but appreciable serum T increases with tiny doses of hCG:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913032/

As well as considering hCG for TRT purposes, you may also be interested in reading about the use of SERMs such as clomiphene if you haven't already

Indeed! That was one of the things I meant by "multi-modal". That and possibly low-dose AIs, naltrexone, bromocriptine, and other odds and ends. Also, it is debatable if clomiphene is the optimal "phene" for this purpose; there's tamoxiphen[e], raloxifene, toremiphene, etc.This is a ripe area for experimentation, and we have only little real data. I expect that sophisticated cocktails will be developed that will work better than monotherapies.

also sometimes injections of triptorelin have been shown to 'kickstart' a recovery of the HPTA, particularly when the problem seems to be emanating from the pituitary/hypothalamus.

Since triptorelin is used clinically to suppress serum T to castrate-level, I need to find out how it can be used to do the opposite. Low doses, in pulses? Or... what? Do you have experience with this, or know someone who does?

Unfortunately no method has been shown to be universally successful, you need to figure out what works for you, so keep an open mind.

Yes. My mind is so open, my brains are falling out. ;-)

Thanks for writing.

 

[Genetic Freak]

What "poor injection methodology" do you perceive?

It's common for IM injections to be given every 2-4 weeks as part of TRT, this has been found to be less than optimal..

Indeed! That was one of the things I meant by "multi-modal". That and possibly low-dose AIs, naltrexone, bromocriptine, and other odds and ends. Also, it is debatable if clomiphene is the optimal "phene" for this purpose; there's tamoxiphen[e], raloxifene, toremiphene, etc.This is a ripe area for experimentation, and we have only little real data. I expect that sophisticated cocktails will be developed that will work better than monotherapies.

Clomiphene has been used to some success either alone or in conjunction with hCG, and/or hMG, unfortunately in most cases favourable results only lasted throughout treatment, and returned to normal upon cessation...

Of note from your paper:

Normal men appear to be more sensitive to hCG than infertile men with hypogonadotropic hypogonadism. This difference in sensitivity is likely due to the fact that steroidogenesis in men with long-term gonadotropin deficiency is impaired, possibly secondary to Leydig cell immaturity.

An additional weakness of our study is that despite the knowledge that serum hormone concentrations fluctuate with circadian rhythms, aspirations were not performed at a standardized interval after identified LH pulses, which may have increased the variance of intratesticular androgen measurements.

What the paper doesn't supply is data 3-6 months post cessation of hCG treatment...

 

[alan2102]

It's common for IM injections to be given every 2-4 weeks as part of TRT, this has been found to be less than optimal..

Oh, ok. I thought he was referring to technique of injection. Yes, of course 2-4 weeks is too long.

Clomiphene has been used to some success either alone or in conjunction with hCG, and/or hMG, unfortunately in most cases favourable results only lasted throughout treatment, and returned to normal upon cessation...

If we're talking about TRT/HRT-type purposes (chronic treatment of a condition not expected to improve) then it would be expected that the results would expire on cessation. We expect that we're going to have to keep doing it forever. But if we're talking about PCT, then of course it is different. Speaking of which, what do you think of that item posted a few months ago by CFC, titled "most AAS users fail to recover natural test levels"? This item suggests that PCT is not nearly as effective as usually supposed. Are high-dose AAS guys inducing irreversible early-onset hypogonadism? An open question.

Of note from your paper:
Normal men appear to be more sensitive to hCG than infertile men with hypogonadotropic hypogonadism. This difference in sensitivity is likely due to the fact that steroidogenesis in men with long-term gonadotropin deficiency is impaired, possibly secondary to Leydig cell immaturity.

Yes, but "appear to be more sensitive" is a wild understatement relative to the earlier-cited link that showed negligible effects on serum T of 10,000 IUs per week in hypogonadotropic hypogonadal men. We're talking at least one and nearly two orders of magnitude dose difference.

Suffice to say there's a lot of unknowns in this, and response to hCG can clearly vary a great deal. Personal experimentation will have to rule for now. I don't see how anyone can make an accurate prediction in any given case. It will work great for some, good for some, fair for some, and lousy or not at all for others.

And, btw, I would think that huge doses like 10,000 IUs per week would result in nad burnout and primary hypogonadism, sooner or later. How much stimulation can the testicles take? I need to investigate further. If you have any thoughts or links, I'm all ears.

Thanks for writing! I enjoy the conversation. Stimulates the brain cells.

 

[CFC]

Since triptorelin is used clinically to suppress serum T to castrate-level, I need to find out how it can be used to do the opposite. Low doses, in pulses? Or... what? Do you have experience with this, or know someone who does?

Triptorelin acetate - as a single 100mcg injection - gained popularity a few years ago, after some Italian researchers tried it successfully on a bodybuilder in 2010. A free analysis of the paper can be found >>here<<. It's been used by quite a number of bodybuilders since.

I've also advised a number of guys to try it over the last 5-6 years. In online forums, some claim the restoration of their HPTA has been permanent; I'm yet to observe that myself. It seems to get perhaps half just back into 'normal' T range for a few months, then usually requires another injection 6-12 months later to maintain. For the rest, it doesn't seem to make any difference at all to serum T after 1-2 months, and only a slight improvement in the weeks after the shot.

Considering triptorelin is likely to exert its effect specifically against the HP (perhaps like a reset switch, or kickstart?), you'd not expect it to help those suffering from primary hypogonadism with recovered LH/FSH levels, but interestingly it has.

This item suggests that PCT is not nearly as effective as usually supposed. Are high-dose AAS guys inducing irreversible early-onset hypogonadism? An open question.

Absolutely they are. We would dearly love and await more (indeed any) solid research into the issue. Supraphysiological doses of AAS seem to induce a combination of both primary and secondary hypogonadism.

In terms of primary hypogonadism, it's probably the result of massive Leydig cell death and fibrosis in the testes, caused by an overwhelming excess of free-radicals from the conversion of test to oestrogen via aromatase.

As for secondary HH, the picture's not so clear - elevated oestrogen has been shown to be potentially neuroprotective with AAS use, but perhaps does little to protect specifically the HP. Or perhaps it's more to do with alterations to GnRH signalling, pulsatility etc.

I would think that huge doses like 10,000 IUs per week would result in nad burnout and primary hypogonadism, sooner or later. How much stimulation can the testicles take?

The desensitisation hypothesis is generally followed by the majority of bodybuilders, though much of the research is not really conclusive and much indirect eg via rodent/in vitro etc.


Is your interest in TRT/HH for your own recovery, or are you just intellectually curious?

 

[alan2102]

Triptorelin acetate - as a single 100mcg injection - gained popularity a few years ago, after some Italian researchers tried it successfully on a bodybuilder in 2010. A free analysis of the paper can be found >>here<<. It's been used by quite a number of bodybuilders since.
I've also advised a number of guys to try it over the last 5-6 years. In online forums, some claim the restoration of their HPTA has been permanent; I'm yet to observe that myself. It seems to get perhaps half just back into 'normal' T range for a few months, then usually requires another injection 6-12 months later to maintain. For the rest, it doesn't seem to make any difference at all to serum T after 1-2 months, and only a slight improvement in the weeks after the shot.
Considering triptorelin is likely to exert its effect specifically against the HP (perhaps like a reset switch, or kickstart?), you'd not expect it to help those suffering from primary hypogonadism with recovered LH/FSH levels, but interestingly it has.

Fascinating. A powerful tool for secondaries, at least some of them. I thought that the gonadal suppression from triptorelin was probably resulting from high-dose bombardment and consequent reactive shutdown. But lower doses at long intervals... the opposite. Thanks for the links.

re: high-dose AAS users causing persistent hypogonadism:
Absolutely they are. We would dearly love and await more (indeed any) solid research into the issue. Supraphysiological doses of AAS seem to induce a combination of both primary and secondary hypogonadism.
In terms of primary hypogonadism, it's probably the result of massive Leydig cell death and fibrosis in the testes, caused by an overwhelming excess of free-radicals from the conversion of test to oestrogen via aromatase.
As for secondary HH, the picture's not so clear - elevated oestrogen has been shown to be potentially neuroprotective with AAS use, but perhaps does little to protect specifically the HP. Or perhaps it's more to do with alterations to GnRH signalling, pulsatility etc.

My growing impression is that deca and the other 19-nors are more the culprit than others. I predict that the worst persistent suppression will be found in bigtime 19-nor users. Nandrolone is toxic to the testicles in addition to causing (so it is said) the most profound hypothal/pit suppression. A one-two punch. This goes to your idea of combined primary and secondary. Testosterone itself actually seems to protect the testicles, as does melatonin. And I don't have to tell you about taurine. ;-)

Re: "free-radicals from the conversion of test to estrogen via aromatase": inflammation and oxidative stress are associated with higher aromatase activity; it is implied in the literature that they might be causal of higher aromatase activity. But I did not know that aromatase itself generated free radicals. Does it?

Is your interest in TRT/HH for your own recovery, or are you just intellectually curious?

Both, and more. I am planning to put my intellectual curiosity, and literature and notes collections, to good use, in a website. I'm working on it, and you are helping. (Thanks.) The T space has a lot of players, but I think I have enough that is novel and useful to justify a new entry. It will certainly NOT be one of those worthless "test-booster" shilling sites, that's for damn sure. They will be among my targets for hostile fire. I'm fed up with that shit, which is spewed out endlessly. We need more voices calling it out, since so many people continue to get suckered.

 

[CFC]

My growing impression is that deca and the other 19-nors are more the culprit than others. I predict that the worst persistent suppression will be found in bigtime 19-nor users. Nandrolone is toxic to the testicles in addition to causing (so it is said) the most profound hypothal/pit suppression. A one-two punch. This goes to your idea of combined primary and secondary. Testosterone itself actually seems to protect the testicles, as does melatonin. And I don't have to tell you about taurine. ;-)

Certainly nandrolone metabolism results in suppressive byproducts (metabolites) that can remain in circulation for a long time (12 months or more), which is probably its worst trait. However I suspect the general toxicity of AAS is more widespread than just 19-nors unfortunately; even plain testosterone, boldenone, or DHT derivatives appear capable of potently upregulating inflammatory factors (TGF-a, cytokines etc), raising NO synthase activity (elevated NO can act as an oxidant in testes and inhibit test secretion from Leydig cells). Even, for example, stanozolol acts directly as an oestrogen, boosts aromatase activity and thus also secondary oestrogen output despite being 'non-aromatisable'. All of these things can add to the milieu increasing free-radical generation and inflammatory processes in the testes, as well as throughout the body (hepatocytes, arterial endothelium, kidney tubules etc).

Re: "free-radicals from the conversion of test to estrogen via aromatase": inflammation and oxidative stress are associated with higher aromatase activity; it is implied in the literature that they might be causal of higher aromatase activity. But I did not know that aromatase itself generated free radicals. Does it?

Think of aromatase as a polluting, free-radical generating 'factory', taking in testosterone, hydroxylating it multiple times and oxidating off methyl groups as carboxylic acids (eg formate), in the production of oestrogens/oestradiol. If concentrations of aromatase and testosterone rise in tandem beyond physiological norms, the stage is set for free-radical generation that can rapidly overload innate anti-oxidative mechanisms (GSH etc), causing apoptosis of neighbouring cells and ultimately inflammation that can then aggravate the whole situation in a viscious positive-feedback cycle. Also bear in mind that oestrogens churned out from that 'factory' and subsequently metabolised can themselves become problematic eg catechol oestrogens, while even 17-B-oestradiol has been shown to be innately toxic, genotoxic and carcinogenic in certain situations/organs, largely via free-radical generating behaviour/activation.

Both, and more. I am planning to put my intellectual curiosity, and literature and notes collections, to good use, in a website. I'm working on it, and you are helping. (Thanks.) The T space has a lot of players, but I think I have enough that is novel and useful to justify a new entry. It will certainly NOT be one of those worthless "test-booster" shilling sites, that's for damn sure. They will be among my targets for hostile fire. I'm fed up with that shit, which is spewed out endlessly. We need more voices calling it out, since so many people continue to get suckered.

Excellent, good luck with this mate. Give us a link when you're ready to go, I'd like to see what you get together.

 

[basix]

Both, and more. I am planning to put my intellectual curiosity, and literature and notes collections, to good use, in a website. I'm working on it, and you are helping. (Thanks.) The T space has a lot of players, but I think I have enough that is novel and useful to justify a new entry. It will certainly NOT be one of those worthless "test-booster" shilling sites, that's for damn sure. They will be among my targets for hostile fire. I'm fed up with that shit, which is spewed out endlessly. We need more voices calling it out, since so many people continue to get suckered.

Hey Alan - Curious about your venture/website. Since beginning TRT I've considered starting something similar. It's a fast growing space with tons of opportunity, especially outside the USA. Will take it to PM.

 

[alan2102]

Excellent, good luck with this mate. Give us a link when you're ready to go, I'd like to see what you get together.

Yo. There will not likely be much that you don't already know. You're way ahead. My target audience will be ordinary guys without multiple advanced degrees in biochemistry and physiology, who want reasonably-reliable practical information. But I will also have a liberal sprinkling of scholarly/nerdy stuff.

Your comments have been very helpful. Thanks. I had not appreciated testosterone and estrogen as oxidative stresses, as such; that's an angle I will investigate further.

One question, however, re this: "even plain testosterone...appears capable of potently upregulating inflammatory factors (TGF-a, cytokines etc), raising NO synthase activity (elevated NO can act as an oxidant in testes and inhibit test secretion from Leydig cells)"

OK. But how does that square with literature suggesting testicular protection by testosterone? Like:

Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice. Environ Toxicol. 2016 Feb;31(2):142-53. doi: 10.1002/tox.22029. PMID: 25077688

Recovery of lead-induced suppressed reproduction in male rats by testosterone. Andrologia. 2015 Jun;47(5):560-7. doi: 10.1111/and.12303. PMID: 24909355

The effect of testosterone propionate supplement on testicular toxicity with thiamphenicol in male Sprague-Dawley rats. J Toxicol Sci. 2004 Aug;29(3):187-93. PMID: 15467268 Free Article

Preventive role of exogenous testosterone on cisplatin-induced gonadal toxicity: an experimental placebo-controlled prospective trial. Fertil Steril. 2010 Mar 15;93(5):1388-93. doi: 10.1016/j.fertnstert.2009.02.028. PMID: 19362306

... does the described protection happen in spite of upreg of inflammatory pathways, etc.?

In fairness, one can also find suchlike:

Prolonged in vivo administration of testosterone-enanthate, the widely used and abused anabolic androgenic steroid, disturbs prolactin and cAMP signaling in Leydig cells of adult rats. J Steroid Biochem Mol Biol. 2015 May;149:58-69. doi: 10.1016/j.jsbmb.2015.01.012. PMID: 25603467

..............

Also: you seem to be highly skeptical about the use of AAS; you are as informed about the potential harms as anyone, anywhere. But you're also the moderator of the PEDs forum on bluelight. Not that those things are necessarily incompatible, but... it would seem a difficult juggling act. How do you manage it? Are you an AAS user yourself? Perhaps a former user, now having misgivings? Do you think that AAS can be used safely at all? Do you disapprove of all AAS use? Etcetera. I'm curious. You're obviously a very smart and conscientious guy. I'm sure you've already visited the questions I ask.

..........................

PS: a ha:

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells. Asian J Androl. 2011 May;13(3):432-7. doi: 10.1038/aja.2010.159. Epub 2011 Feb 7. PMID: 21297653

Nice! Tends to confirm my "less is (often, usually) more" bias. Higher doses impose oxidative stress; lower doses reduce oxidative stress.

 

[alan2102]

Hey Alan - Curious about your venture/website. Since beginning TRT I've considered starting something similar. It's a fast growing space with tons of opportunity, especially outside the USA. Will take it to PM.

Sure thing! Let's chat.

 

[CFC]

One question, however, re this: "even plain testosterone...appears capable of potently upregulating inflammatory factors (TGF-a, cytokines etc), raising NO synthase activity (elevated NO can act as an oxidant in testes and inhibit test secretion from Leydig cells)"

OK. But how does that square with literature suggesting testicular protection by testosterone? Like:

Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice. Environ Toxicol. 2016 Feb;31(2):142-53. doi: 10.1002/tox.22029. PMID: 25077688

Recovery of lead-induced suppressed reproduction in male rats by testosterone. Andrologia. 2015 Jun;47(5):560-7. doi: 10.1111/and.12303. PMID: 24909355

The effect of testosterone propionate supplement on testicular toxicity with thiamphenicol in male Sprague-Dawley rats. J Toxicol Sci. 2004 Aug;29(3):187-93. PMID: 15467268 Free Article

Preventive role of exogenous testosterone on cisplatin-induced gonadal toxicity: an experimental placebo-controlled prospective trial. Fertil Steril. 2010 Mar 15;93(5):1388-93. doi: 10.1016/j.fertnstert.2009.02.028. PMID: 19362306

... does the described protection happen in spite of upreg of inflammatory pathways, etc.?

In fairness, one can also find suchlike:

Prolonged in vivo administration of testosterone-enanthate, the widely used and abused anabolic androgenic steroid, disturbs prolactin and cAMP signaling in Leydig cells of adult rats. J Steroid Biochem Mol Biol. 2015 May;149:58-69. doi: 10.1016/j.jsbmb.2015.01.012. PMID: 25603467

First, I should clarify that T is in no way bad or inflammatory by definition; quite the opposite. But like with many things, it's getting the right amount that matters. Too much or too little can be equally bad for the body. This is comparable to how the various oxidative species, at the right level, are critical to the body's basic functioning. And also why high doses of anti-oxidants can be both toxic and carcinogenic.

With regards to the specific papers you've listed, it's not exactly T providing 'protection' in any real sense. What they discovered is that exogenous T + toxic chemical is so deleterious that it places germ cells in the testes into a state of protective dormancy. The theory goes that since DNA isn't rapidly replicating, there are fewer opportunities for cells to become malignant and thus apoptotic. Which means that when treatment ends, a natural rebound can occur from a more abundant pool of healthy functioning cells.

The main problem translating this neat theory to humans is that exogenous T alone, even at high doses, appears unable to achieve the required degree of dormancy without (presumably) the addition of an undesirable toxic agent. We would base this logic on the fact that (1) many AAS users are still able to produce viable sperm (and create babies) even on extremely heavy cycles, and (2) most men who've played around with AAS experience appalling rates of recovery (ie, germ cells are not sufficiently dormant). The notoriously poor reliability of AAS as a contraceptive further supports this.

Also: you seem to be highly skeptical about the use of AAS; you are as informed about the potential harms as anyone, anywhere. But you're also the moderator of the PEDs forum on bluelight. Not that those things are necessarily incompatible, but... it would seem a difficult juggling act. How do you manage it? Are you an AAS user yourself? Perhaps a former user, now having misgivings? Do you think that AAS can be used safely at all? Do you disapprove of all AAS use? Etcetera. I'm curious. You're obviously a very smart and conscientious guy. I'm sure you've already visited the questions I ask.

I don't agree with your assessment at all; rather, I'm a skeptic of AAS use as promoted by many other people.

I'm a cautious user now, and did the kind of reckless things in my youth I would try to discourage others from doing today. But I certainly think there's a role for AAS in performance enhancement.

Bodybuilding is an activity that for most people requires years of long-term consistency, repetition and discipline for an athlete to close in on their potential, even with AAS. The challenge we face as an harm-reduction site is that most other AAS forums promote the idea, intentionally or otherwise, that this can be achieved almost overnight.

In order to do that, the doses used and practices promoted - such as blasting and cruising and extreme polypharmacy - push the risk-benefit ratio far into the risk zone. And for no practical reason at all: most men simply cannot hold or maintain the kind of blubbery mass they think they're gaining off of one or two of these cycles. In the long run it's a complete waste of time and money, and self-evidently a delusion to imagine they're 'gaining' 20lbs every cycle when they lose most of it afterwards.

So why do it, and why risk health like that, when an approach that instead maximises gains from the smallest amounts possible without the crazy yo-yoing - instead optimising all other variables like diet and training - is ultimately going to achieve a similar yet more sustainable outcome in the long run, minus the potentially tragic health outcomes?

To promote this doesn't make me a skeptic of AAS, just logical.

 

[alan2102]

First, I should clarify that T is in no way bad or inflammatory by definition; quite the opposite. But like with many things, it's getting the right amount that matters. Too much or too little can be equally bad

"Only the dose makes the poison" has always been my rallying-cry.

With regards to the specific papers you've listed, it's not exactly T providing 'protection' in any real sense. What they discovered is that exogenous T + toxic chemical is so deleterious that it places germ cells in the testes into a state of protective dormancy. The theory goes that since DNA isn't rapidly replicating, there are fewer opportunities for cells to become malignant and thus apoptotic. Which means that when treatment ends, a natural rebound can occur from a more abundant pool of healthy functioning cells.

I'll have to defer to your superior knowledge. But, lingering:
1. The lead (Pb) one looked like real protection.
2. There's more to testicles than germ cells, and more to testicular function than fertility.
3. Don't forget PMID: 21297653. Low-dose T IS protective.

I'm a cautious user now, and did the kind of reckless things in my youth I would try to discourage others from doing today. But I certainly think there's a role for AAS in performance enhancement.

I suspected as much.

the doses used and practices promoted - such as blasting and cruising and extreme polypharmacy - push the risk-benefit ratio far into the risk zone.

Generally I agree. However, I still have questions. The big one is: "show me the bodies" and, closely linked, "how did they die?". I see that high-AAS-using bodybuilders are indeed dropping dead terribly often. But it seems that they are dying of cardiovascular and renal diseases, mostly, and a few cancers, like liver. If all AAS's are seriously toxic to the testicles, inducing uncontrolled free radical pathology there, why are we not seeing a bunch of testicular cancers? Or perhaps some other testicular diseases? Also, why are we not seeing more cancers, generally?

Also, it is good to remember that some of our concern is relevant largely to younger guys who want to preserve testicular function. If you're old and ready to go on TRT forever, then... well, who cares if the practice in question might screw up your nads? They're history anyway, in practice. Yes, I know, the practices in question might screw up other tissues as well. I'm not urging recklessness. But for older men who are giving up on natural way, I don't see what is wrong necessarily with a bit of MILD blasting, interspersed with the cruising, for example. Nothing extreme, of course, and always surrounded by a battery of protective orthomolecular supplements. As you say, "there's a role for AAS in performance enhancement", provided it is done intelligently, at reasonable doses, with protective adjuncts. That's my view, anyway -- subject to change, if I am compelled to.

why risk health...when an approach that instead maximises gains from the smallest amounts possible without the crazy yo-yoing - instead optimising all other variables like diet and training - is ultimately going to achieve a similar yet more sustainable outcome in the long run, minus the potentially tragic health outcomes?

Totally agreed.

That, btw, is why I was enthusiastic (you might have noticed, on this forum) about that guy's low-dose stanozolol experience. Maximizing gains from the smallest amounts possible, indeed. An inspiring story. I'll bet there's a world of potential with low doses, yet to be discovered. But the narrative has been dominated by the high-dose people and the (outrageous and unrealistic) images that they project in their media. They've not only skewed the narrative in terms of doses, they've skewed popular perceptions of what a good male body looks like.

Is the "extreme polypharmacy" that you denounce extreme because it is poly, or are you referring to the reckless doses? I would like to see, experimentally, polypharmacy of the sort used by the high-dose AAS crowd, BUT using much lower doses, perhaps 1/10th as much, or 1/5th. My hunch is that some very nice results would be forthcoming -- with minimal risk. No Mr Universe overnight, but no dropping dead at ~45 of a massive heart attack, either. %)

To promote this doesn't make me a skeptic of AAS, just logical.

You're very much a skeptic! Being skeptical does not mean being negative or opposed; just circumspect, cautious and critical. Which is the right way to be.

 

[CFC]

Generally I agree. However, I still have questions. The big one is: "show me the bodies" and, closely linked, "how did they die?". I see that high-AAS-using bodybuilders are indeed dropping dead terribly often. But it seems that they are dying of cardiovascular and renal diseases, mostly, and a few cancers, like liver. If all AAS's are seriously toxic to the testicles, inducing uncontrolled free radical pathology there, why are we not seeing a bunch of testicular cancers? Or perhaps some other testicular diseases? Also, why are we not seeing more cancers, generally?

Also, it is good to remember that some of our concern is relevant largely to younger guys who want to preserve testicular function. If you're old and ready to go on TRT forever, then... well, who cares if the practice in question might screw up your nads? They're history anyway, in practice. Yes, I know, the practices in question might screw up other tissues as well. I'm not urging recklessness. But for older men who are giving up on natural way, I don't see what is wrong necessarily with a bit of MILD blasting, interspersed with the cruising, for example. Nothing extreme, of course, and always surrounded by a battery of protective orthomolecular supplements. As you say, "there's a role for AAS in performance enhancement", provided it is done intelligently, at reasonable doses, with protective adjuncts. That's my view, anyway -- subject to change, if I am compelled to.

I appreciate that your area of interest is TRT and the testes, which is why you're focusing your attention on that as if it's the issue I'm discussing here. However most of our concern regarding long-term AAS risks comes down to those cardiovascular, renal, psychological issues etc you're passing by. And when I talk about risks and harms, I'm referring to all of them.

We've discussed repeatedly and in considerable depth on here some of the challenges faced; read through some of the threads and studies in the harms section of the study corner to save me repeating myself.

If you're suggesting these are not serious issues and 'dead bodies' (see Big Dead Bodybuilders), I'm afraid I can't agree with you at all. I also have too much personal experience in this matter, having seen friends and acquaintances suffer much too young. Few coroners will ever write down 'died of steroids', and yet a prematurely enlarged prostate, insulin overdose, or heart attack or stroke from an hypertrophied heart or blood clot in your twenties, thirties or forties in otherwise healthy men is neither normal nor coincidental.

That, btw, is why I was enthusiastic (you might have noticed, on this forum) about that guy's low-dose stanozolol experience. Maximizing gains from the smallest amounts possible, indeed. An inspiring story. I'll bet there's a world of potential with low doses, yet to be discovered. But the narrative has been dominated by the high-dose people and the (outrageous and unrealistic) images that they project in their media. They've not only skewed the narrative in terms of doses, they've skewed popular perceptions of what a good male body looks like.

I agree, and I'm glad he's appearing to find benefit. Also regarding specifically that, bear in mind winstrol does come in 4mg tablets, hence clearly it has established efficacy at low doses for certain populations (mostly women and juveniles, probably hypogonadic men and others).

Is the "extreme polypharmacy" that you denounce extreme because it is poly, or are you referring to the reckless doses? I would like to see, experimentally, polypharmacy of the sort used by the high-dose AAS crowd, BUT using much lower doses, perhaps 1/10th as much, or 1/5th. My hunch is that some very nice results would be forthcoming -- with minimal risk. No Mr Universe overnight, but no dropping dead at ~45 of a massive heart attack, either. %)

Extreme because it's usually both to be honest. For anyone with experience in what they're doing, the approach you suggest works fine. But I'm not here to advise that to beginners for obvious reasons, and most people who ask advice here aren't very experienced. As always, advice is tailored to situation. For people that pay me to get them in contest shape, I may take all kinds of approaches that I would never want to advise here to complete strangers. I'm sure you can understand.

 

[alan2102]

most of our concern regarding long-term AAS risks comes down to those cardiovascular, renal, psychological issues etc you're passing by. And when I talk about risks and harms, I'm referring to all of them.... If you're suggesting these are not serious issues and 'dead bodies' (see Big Dead Bodybuilders), I'm afraid I can't agree with you at all.

CFC, I don't understand. I wrote:

"I see that high-AAS-using bodybuilders are indeed dropping dead terribly often. But it seems that they are dying of cardiovascular and renal diseases, mostly, and a few cancers, like liver."

I don't know how I can be more clear than that. Yes, these are certainly serious issues, and I am not passing by the cardiovascular and renal diseases that are killing these men! The question I led to was: how come not more testicular cancers and other testicular diseases, and more cancers in general? Probably not a question that can be answered. But I was underscoring how limited we are when it comes to extrapolation from our animal studies and biochemical pathways and whatnot. It is all great, but the bottom line is: let's look at the bodies. How did they die?

Yes, so many bodybuilders dropping dead in their prime -- 50s, 40s, even 30s -- is tragic and alarming. I wish the governing or official bodies would institute controls to reduce the risk. I mean, not so much drug testing, as episodic physiological testing to see whether or not these guys are killing themselves. For example, why not run lipid panels every few months on all competitive builders, for at least a year before competition, to ensure that they're not at running HDL under 20, or suchlike (i.e. to ensure that they're not killing themselves with an excess of steroids). Same with kidneys: do microalbuminuria determinations, or whatever else. Then, if you're killing yourself, you're disqualified from competition. In other words, let the standard be health, and not drugs *per se*. You can use drugs, but you can't kill yourself with them. Just a thought.

Thanks for all your comments. This discussion has been very rewarding for me.

I will be away from my machine for a week or so starting tomorrow, so won't be back for a while. Late next week, probably.

Thanks!

Alan

 

[CFC]

Ah ok sorry, I think we're talking slightly at cross-purposes. But anyway yes I agree, there's no obvious sign of any uptick in testicular cancer, which you might assume there would be.

Some thoughts on that: perhaps if all guys cycled were high doses of stanozolol and nandrolone (say), then there might be? But that doesn't happen in the real world. Perhaps also the shutdown and reduced cellular activity that AAS seems to be causing over the longer-term (even years post-cycle) works in our favour on this. There is some research suggesting this may be the case, mechanistically not entirely unlike the proposed mechanism of toxin + AAS papers above. The ability of AAS to lengthen telomeres may also counteract any malignant tendencies induced by free-radicals and inflammation, which would be more noticeable in tissues with rapidly dividing cells like the testes (and liver, marrow etc).

As you allude, we don't really have enough (barely any) human research to speculate too far, since rodent-based or petri-dish findings have frequently been shown not to reflect human physiology. Either way, a complex picture, and none of this stuff is black and white. Regardless I don't think that modestly supraphysiological doses of AAS would be harmful for most men either in the testes or elsewhere. Only the more extreme practices.