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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.
========================================================
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.