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STENDEC

The Power of Androgens

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J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1276-1294. 
Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.
Gharahdaghi N1, Rudrappa S1, Brook MS1, Idris I1, Crossland H1, Hamrock C2, Abdul Aziz MH1, Kadi F3, Tarum J3, Greenhaff PL4, Constantin-Teodosiu D4, Cegielski J1, Phillips BE1, Wilkinson DJ1, Szewczyk NJ1, Smith K1, Atherton PJ1.

BACKGROUND:
The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short-term RET remain poorly defined.

 

METHODS:
Eighteen non-hypogonadal healthy older men, 65-75 years, were assigned in a random double-blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole-body RET (three sets of 8-10 repetitions at 80% one-repetition maximum). Subjects underwent dual-energy X-ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D2 O), and breakdown (extrapolated).

 

RESULTS:
Testosterone adjuvant to RET augmented total fat-free mass (P=0.007), legs fat-free mass (P=0.02), and appendicular fat-free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross-section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70°) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 ± 0.21%·day-1 vs. P: 1.34 ± 0.13%·day-1 , P=0.0009) and absolute breakdown rates (T: 140.2 ± 15.8 g·day-1 vs. P: 90.2 ± 11.7 g·day-1 , P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 ± 1.4 g·day-1 vs. P: 1.9 ± 1.2 g·day-1 , P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4-fold; Srd5a1: 1.6-fold; AKR1C3: 2.1-fold; and HSD17β3: two-fold); insulin-like growth factor (IGF)-1 signalling [IGF-1Ea (3.5-fold) and IGF-1Ec (three-fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up-regulated with T therapy. Only T up-regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 ± 0.2-fold, P=0.0002), in addition to peroxisome proliferator-activated receptor-γ co-activator 1-α mRNA (1.19 ± 0.21-fold, P=0.037).

 

CONCLUSIONS:
Administration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up-regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short-term intervention to improve muscle mass/function in older non-hypogonadal men.

 

PMID: 31568675 

 

FFT

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35 minutes ago, STENDEC said:

We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage.

I'm having trouble sorting out what this implies -- how would you apply these conclusions in real life?

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15 minutes ago, Sanction said:

I'm having trouble sorting out what this implies -- how would you apply these conclusions in real life?

 

Testosterone by itself, even in amounts that produce supraphysiological levels, does not reliably cause testicular shutdown....and, at those doses,  also doesn't produce any significant negative health effects at least over six months of the study.

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1 minute ago, STENDEC said:

 

Testosterone by itself, even in amounts that produce supraphysiological levels, does not reliably cause testicular shutdown....and, at those doses,  also doesn't produce any significant negative health effects.

Okay, but shutdown and PCT happen in anecdotal real life. So, how do I reconcile these? #confused

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1 hour ago, Sanction said:

Okay, but shutdown and PCT happen in anecdotal real life. So, how do I reconcile these? #confused

 

Anecdotal being the operative word. I suspect that, generally speaking, the fear of shutdown among AAS users is a lot more real than shutdown itself. The lifting world tends to rapidly convert the hypothetical to gospel (see also: protein requirements and fear of GH "bleed" from peptides).

 

The other thing to note here is the dose. A weekly dose of 300mg of long-acting testosterone will put the average guy at the very high end of "normal" somewhere between 1100-1500ng/dl which while high, isn't over the moon.

 

That sort of dose isn't even a noob PED dose anymore and at gram plus doses of T plus whatever is getting stacked on top, suppression may very well be a much bigger issue.

 

Last observation, we are talking about testosterone here. IME, stuff that plays on the progesterone receptor like Deca and Tren are orders of magnitude more suppressive and research on hormonal male contraceptives bears this out.

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4 hours ago, STENDEC said:

 

Anecdotal being the operative word. I suspect that, generally speaking, the fear of shutdown among AAS users is a lot more real than shutdown itself. The lifting world tends to rapidly convert the hypothetical to gospel (see also: protein requirements and fear of GH "bleed" from peptides).

 

The other thing to note here is the dose. A weekly dose of 300mg of long-acting testosterone will put the average guy at the very high end of "normal" somewhere between 1100-1500ng/dl which while high, isn't over the moon.

 

That sort of dose isn't even a noob PED dose anymore and at gram plus doses of T plus whatever is getting stacked on top, suppression may very well be a much bigger issue.

 

Last observation, we are talking about testosterone here. IME, stuff that plays on the progesterone receptor like Deca and Tren are orders of magnitude more suppressive and research on hormonal male contraceptives bears this out.

To add on, this analysis was looking at sperm production and upstream markers. While I think the risk of permanent shutdown is overplayed, it's a real thing that happens. This forum is miniscule, and I bet our experiences interacting with people might not be statistically meaningful. I'd urge anyone to venture to a larger board, like Anabolic Minds, and peruse the TRT intro threads and see how many reports there are of users running some cycles, running PCT, and being unable to recover (even after conventional TRT methods like employing SERMs). Even if the chances of it happening are small, it's worth being informed and understanding that this is a risk. 

 

I think the paper at hand is far more valuable in terms of thinking about fertility and the acute and long-term implications of AAS use. T-therapy would be wholly inadequate as a standalone contraceptive, even at upwards of 300mg/week. PED use does have a dose-effect inhibitory relationship on spermatogenesis that seems to plateau around 100mg/week (but might re-peak at higher doses above 300mg e.g. 600mg/week). And lastly, I think this helps make sense of other anecdotes of users who are playing experimental chemistry with their bodies and still end up impregnating a person, including after a cycle, during PCT, and even while on cycle. 

 

Also, very good points about other types of AAS and how they may have different impacts than testosterone, an endogenous hormone. 

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One other thought: there is undoubtedly a very high amount of interpersonal variability here, specifically related to the expression of aromatase. The HPT Axis is much more sensitive to elevated estrogen than to elevated androgens so that may have a significant impact on how suppressive a given dose of testosterone is.

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3 hours ago, Growth Factor said:

This forum is miniscule, and I bet our experiences interacting with people might not be statistically meaningful. I'd urge anyone to venture to a larger board, like Anabolic Minds, and peruse the TRT intro threads and see how many reports there are of users running some cycles, running PCT, and being unable to recover (even after conventional TRT methods like employing SERMs). Even if the chances of it happening are small, it's worth being informed and understanding that this is a risk. 

 

Truth, this forum is minuscule, and our n=like 5 these days. I have been around the block a LONG TIME, though, and I have experience on TRT fora and muscle fora and drug fora for well over a decade. One thing I can tell you about that is that in my estimation, men in general, young men in particular, young and older men who are concerned about looks, sex drive, attractiveness, etc.-they are given to histrionics. They are given to anxiety, and to chronic dysmorphia, and other mental illnesses that many times trumps all measurable hormonal issues.

 

I used to spend some time on Dr. Michael Scally's FB group for TRT. They are all pathological. One guy had been tested for every hormonal issue known to mankind. His bloods were all unremarkable. His T levels were on the lower end, but in his late 40s or early 50s being in the 300s isn't awful. Yet he was stuck on the idea that he had a T issue, and not that it was his alcohol intake, his depression, his chronic insomnia, his obsessive working out, etc. 

 

And this guy isn't really an exception in my experience, he's more of the rule. He's the rule, and there are legions of men out there who will enable this sort of thinking with their G+ dosages, obsessive anti-E consumption, and other stuff. It's really quite nutty. 

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12 hours ago, Emperor G_D said:

men in general, young men in particular, young and older men who are concerned about looks, sex drive, attractiveness, etc.-they are given to histrionics

 

x100

 

I think the take home message about suppression is this: exogenous androgens can be, and probably will be, suppressive of natural testosterone production in a dose and substance-dependant manner. That said, the human body is an amazing self-righting machine and I suspect under most circumstances, any suppression you might experience will resolve itself without heroic intervention once the exogenous androgens are withdrawn.

 

How concerned you should be about suppression, which is a different question than whether or not it happens, depends entirely on how old you are, your plans for having kids, the cycle you are contemplating and your willingness to spend the rest of your life on some sort of TRT if things really go off the rails.

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