# Exogenous test-E and its side effects (or not) in both younger and older men.



## Trouble (Aug 3, 2006)

Finally found very solid set of citations that demonstrates no significant adverse effects for simple exogenous test E use in young men with normal sex hormone production, but indicates that older men are more sensitive to side-effects (most likely via changes in liver function and cortisol activity) to exogenous test.  Also, there were interesting differences in brain function and mood effects from test when cohorts of older and younger test subjects were compared over a large dose range.

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_The Effects of Varying Doses of T on Insulin Sensitivity, Plasma Lipids, Apolipoproteins, and C-Reactive Protein in Healthy Young Men.  _

Atam B. Singh, Stanley Hsia, Petar Alaupovic, Indrani Sinha-Hikim, Linda Woodhouse, Thomas A. Buchanan, Ruoquing Shen, Rachelle Bross, Nancy Berman and Shalender Bhasin.   The Journal of Clinical Endocrinology & Metabolism 87(1): 136-143 (2002).

The effects of T supplementation on insulin sensitivity, inflammation-sensitive markers, and apolipoproteins remain poorly understood. We do not know whether T???s effects on plasma lipids, apolipoproteins, and insulin sensitivity are dose dependent, or whether significant anabolic effects can be achieved at T doses that do not adversely affect these cardiovascular risk factors. 

To determine the effects of different doses of T, 61 eugonadal men, 18???35 yr of age, were randomly assigned to 1 of 5 groups to receive monthly injections of long-acting GnRH agonist to suppress endogenous T secretion and weekly injections of 25, 50, 125, 300, or 600 mg T enanthate for 20 wk. Dietary energy and protein intakes were standardized. 

Combined administration of GnRH agonist and graded doses of T enanthate resulted in nadir T concentrations of 253, 306, 542, 1345, and 2370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Plasma high density lipoprotein cholesterol and apolipoprotein A-I concentrations were inversely correlated with total and free T concentrations and were significantly decreased only in the 600 mg/wk group (change in high density lipoprotein cholesterol: -8 ± 2 mg/dl; P = 0.0005; change in apolipoprotein A-I: -16 ± 2 mg/dl; P = 0.0001). 

Serum total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, apolipoprotein B, and apolipoprotein C-III were not significantly correlated with T dose or concentration. There was no significant change in total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, apolipoprotein B, or apolipoprotein C-III levels at any dose. 

The insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose, derived from the insulin-modified, frequently sampled, iv glucose tolerance test using the Bergman minimal model, did not change significantly at any dose. Circulating levels of C-reactive protein were not correlated with T concentrations and did not change with treatment in any group. Significant increments in fat-free mass, muscle size, and strength were observed at doses that did not affect cardiovascular risk factors.

*Over a wide range of doses, including those associated with significant gains in fat-free mass and muscle size, T had no adverse effect on insulin sensitivity, plasma lipids, apolipoproteins, or C-reactive protein. Only the highest dose of T (600 mg/wk) was associated with a reduction in plasma high density lipoprotein cholesterol and apolipoprotein A-I.* Long-term studies are needed to determine whether T supplementation of older men with low T levels affects atherosclerosis progression.

Full paper, on line (free): http://jcem.endojournals.org/cgi/content/full/87/1/136

Note that plasma estrogen rose for the dose range 300-600 mg.

============ Related Citations =======================

_Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle._ 

Bhasin S, Woodhouse L,  Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE,  Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, and Storer TW.  Division of Endocrinology, Metabolism, and Molecular Medicine, University of California (UCLA).   J Clin Endocrinol Metab. 2005 Feb;90(2):678-88. 

Although testosterone levels and muscle mass decline with age, many older men have serum testosterone level in the normal range, leading to speculation about whether older men are less sensitive to testosterone. We determined the responsiveness of androgen-dependent outcomes to graded testosterone doses in older men and compared it to that in young men. The participants in this randomized, double-blind trial were 60 ambulatory, healthy, older men, 60-75 yr of age, who had normal serum testosterone levels. Their responses to graded doses of testosterone were compared with previous data in 61 men, 19-35 yr old. The participants received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate weekly for 20 wk. Fat-free mass, fat mass, muscle strength, sexual function, mood, visuospatial cognition, hormone levels, and safety measures were evaluated before, during, and after treatment. Of 60 older men who were randomized, 52 completed the study. After adjusting for testosterone dose, changes in serum total testosterone (change, -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, -3.6, +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) levels were dose-related in older men and significantly greater in older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2, +5.6, and +7.3 kg, respectively, in five ascending dose groups) and muscle strength in older men were correlated with testosterone dose and concentrations and were not significantly different in young and older men. Changes in fat mass correlated inversely with testosterone dose (r = -0.54; P < 0.001) and were significantly different in young vs. older men (P < 0.0001); young men receiving 25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and visuospatial cognition did not change significantly in either group. Frequency of hematocrit greater than 54%, leg edema, and prostate events were numerically higher in older men than in young men. 

Older men are as responsive as young men to testosterone's anabolic effects; however, older men have lower testosterone clearance rates, higher increments in hemoglobin, and a higher frequency of adverse effects. Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength.

Full paper, on-line: http://jcem.endojournals.org/cgi/content/full/90/2/678

See also: http://jcem.endojournals.org/cgi/content/full/90/7/3838
_
Dose-Dependent Effects of Testosterone on Sexual Function, Mood, and Visuospatial Cognition in Older Men. _ Peter B. Gray, Atam B. Singh, Linda J. Woodhouse, Thomas W. Storer, Richard Casaburi, Jeanne Dzekov, Connie Dzekov, Indrani Sinha-Hikim and Shalender Bhasin.   Journal of Clinical Endocrinology & Metabolism 90(7):3838-3846 (2005).

CONCLUSIONS: Different aspects of male behavior respond differently to testosterone. When considered together with previous data from young men, these data indicate that testosterone dose-response relationships for sexual function and visuospatial cognition differ in older and young men.


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## Trouble (Aug 3, 2006)

*Related Cool Article*

_Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. _

Storer TW, Magliano L, Woodhouse L,  Lee ML, Dzekov C, Dzekov J, Casaburi R and Bhasin S.  J Clin Endocrinol Metab. 2003  88(4):1478-85.

Full on-line paper: http://jcem.endojournals.org/cgi/content/full/88/4/1478

Testosterone supplementation in men increases fat-free mass, but whether measures of muscle performance, such as maximal voluntary strength, power, fatigability, or specific tension, are improved has not been determined. Furthermore, the extent to which these measures of muscle performance are related to testosterone dose or circulating concentration is unknown. 

To examine the relationship between testosterone dose and muscle performance, 61 healthy, eugonadal young men (aged 18-35 yr) were randomized to 1 of 5 groups, each receiving a long-acting GnRH agonist to suppress endogenous testosterone production plus weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate for 20 wk. These doses produced mean nadir testosterone concentrations of 253, 306, 542, 1345, and 2370 ng/dl, respectively. 

Maximal voluntary muscle strength and fatigability were determined by a seated leg press exercise. Leg power was measured using a validated leg power instrument. Specific tension was estimated by the ratio of one repetition maximum muscle strength to thigh muscle volume determined by magnetic resonance imaging. 

--->Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly correlated with total (r = 0.46; P = 0.0005) and free (r = 0.38; P = 0.006) testosterone as was leg power (total testosterone: r = 0.38; P = 0.007; free testosterone: r = 0.35; P = 0.015), but not muscle fatigability. 

--->Serum IGF-I concentrations were not significantly correlated with leg strength, power, or fatigability. Specific tension did not change significantly at any dose. We conclude that the effects of testosterone on muscle performance are specific; it increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. The changes in leg strength and power are dependent on testosterone dose and circulating testosterone concentrations and exhibit a log-linear relationship with serum total and free testosterone. 

-->Failure to observe a significant testosterone dose relationship with fatigability suggests that testosterone does not affect this component of muscle performance and that different components of muscle performance are regulated by different mechanisms.


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## GFR (Aug 3, 2006)

More good stuff...thanks Trouble


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## Tough Old Man (Aug 3, 2006)

Trouble you be de girl.


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## musclepump (Aug 8, 2006)

This can't be true. Steroids KILL! ALWAYS! EVERY TIME!


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## musclepump (Aug 10, 2006)

Hey Trouble, I just read this again (because I think it's such a goodie), and was caught this time by its mention of benefits at 125mg was "the best trade-off." Is there any additional information as to how much mass was gained in 20 weeks at 125mg, and the average users profile?


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## pengers84 (Aug 14, 2006)

musclepump said:


> Hey Trouble, I just read this again (because I think it's such a goodie), and was caught this time by its mention of benefits at 125mg was "the best trade-off." Is there any additional information as to how much mass was gained in 20 weeks at 125mg, and the average users profile?




Yeah that caught my eye to.  What is everyone elses opinions on a cycle like that?  Would there be much gained? would PCT be required?


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## Trouble (Aug 15, 2006)

Doesn't look like PCT is required at lower doses.  You could use something as stupidly generic as grapefruit eaten a few times a week to counter aromatase activity.

Mass gains (and strength gains) are proportional to dose.  The trade-off would be to settle for a slower, but steady gain in mass. Done right, the retention rate should be very high for mass and strength gains, especially if you are also working to max glucose tolerance and gut absorption kinetics.

Think about that.  There is this possibility that, with careful balancing of these factors, you get the best of both worlds, lean high quality mass, exceptional immune and connective tissue support, good vascularity, minimized liver lipid and liver enzyme effects and minimal perturbation of pancreas, adrenal and thyroid function.

Call it :semi-natural: cycling.


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## pengers84 (Aug 15, 2006)

Hmm well thats very interesting, thanks for shareing that!  

How do you work to max glucose tolerance and gut absorption kinetics?

If you did a cycle like that would you still go by the rule time on=time off?


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## Trouble (Aug 16, 2006)

Cycle frequency and time off would depend on factors such as age, training intensity, time of year (light duration and intensity, and environmental thermal range have an impact on natural test production, as does diet, sleep, and exertion factors), etc.  5-6 months minimum. Think of it as a slow undulation in plasma test concentration, not a choppy saw tooth pattern.  You want time off to be long enough to afford turnover in liver, prostate, skin, gut, where androgen responsive nuclear receptor regulation may be midly altered from elevated exposure to test.

Maximizing glucose tolerance and gut absorption kinetics aren't casual chit chat items. The latter is worth a lot of money in this market.  The former is worth discussing here at length.  Probably in my section, over in Health.  It should be  a prequisite to considering use of AAS; you need several years of dedicated lifestyle changes to help lock in it (to a steady-state metabolic condition).


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## pengers84 (Aug 16, 2006)

Cool, so  I guess your better safe then sorry in terms of time off.  What difference does age (Im 22), training intensity and time of year make?

When you say 'the latter is wort a lot of money,'  what would it take for an average joe like me to get information on this topic?

I just started a thread in the general health forum on glucose tolerance.

Thanks a lot for thee feedback.


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