IGF-1, Testosterone and Cancer

[Holden]

This is a study in young men using different doses of testosterone. You can see the changes in total and free testosterone (increase), sex hormone binding globulin (decrease) and IGF-1 levels (increase only at doses over 125 mg/week)

Testosterone dose-response relationships in healthy young men

Shalender Bhasin, Linda Woodhouse, Richard Casaburi, Atam B. Singh, Dimple Bhasin, Nancy Berman, Xianghong Chen, Kevin E. Yarasheski, Lynne Magliano, Connie Dzekov, Jeanne Dzekov, Rachelle Bross, Jeffrey Phillips, Indrani Sinha-Hikim, Ruoquing Shen, Thomas W. Storer
American Journal of Physiology - Endocrinology and Metabolism Published 1 December 2001 Vol. 281 no. 6, E1172-E1181

View attachment 3303

Abstract
Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18–35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Thanks Nelson, very interesting study. Do you think the IGF-1 levels (increase only at doses over 125 mg/week) can be extrapolated to the real world or do you think the administration of the GnRH agonist might skew that break line? The reason I ask is that the 125 mg / week in this study barely moved the needle, so to speak, on the Total T or the Free T after 16 weeks, but in practice don't we see 125 mg / week having a greater impact in those levels?

 

[CoastWatcher]

Thanks Nelson, very interesting study. Do you think the IGF-1 levels (increase only at doses over 125 mg/week) can be extrapolated to the real world or do you think the administration of the GnRH agonist might skew that break line? The reason I ask is that the 125 mg / week in this study barely moved the needle, so to speak, on the Total T or the Free T after 16 weeks, but in practice don't we see 125 mg / week having a greater impact in those levels?

Wouldn't it (response to 125mg of testosterone per week) depend on factors such as SHBG levels and the treatment protocol (single or multiple injections per week, this study specifically indicated injections were only given weekly)? We do see 125mg have a less than impressive effect when injected in a single dose, as this study did; a far better response is noted when that is divided into more frequent weekly injections.

 

[Nelson Vergel]

Thanks Nelson, very interesting study. Do you think the IGF-1 levels (increase only at doses over 125 mg/week) can be extrapolated to the real world or do you think the administration of the GnRH agonist might skew that break line? The reason I ask is that the 125 mg / week in this study barely moved the needle, so to speak, on the Total T or the Free T after 16 weeks, but in practice don't we see 125 mg / week having a greater impact in those levels?

These were young men. I think age is the main factor in how much IGF-1 increases with larger testosterone doses.

 

[Nelson Vergel]

Testosterone administration increases insulin-like growth factor-I levels in normal men.

Hobbs CJ1, Plymate SR, Rosen CJ, Adler RA.


Abstract

Although testosterone (T) administration can increase insulin-like growth factor-I (IGF-I) when administered to hypogonadal men, no studies have examined whether this occurs in normal men. The present study was undertaken to determine if an increase in IGF-I may be part of the anabolic effect of androgens. We enrolled 11 normal men in a randomized, double-blinded cross-over study. Subjects were assigned to receive either T enanthate (TE) (300 mg im, each week) or nandrolone (ND) decanoate (300 mg im, each week) for 6 weeks. After a washout period subjects were administered the alternate treatment. Pre- and posttreatment serum was analyzed for IGF-I by RIA after acid-ethanol extraction. Results expressed as mean +/- SEM (Table 1). IGF-binding protein-3 was measured by RIA and was unchanged in the TE treatment and decreased significantly after ND treatment. Although GH levels were not significantly different after either TE or ND treatment, they tended to increase after TE treatment (1.23 +/- 0.28 ng/mL vs. 3.3 +/- 1.03 ng/mL) but remained unchanged after ND treatment (1.68 +/- 0.68 ng/mL vs. 1.89 +/- 0.64 ng/mL). Serum total T levels increased 32 +/- 0.05 nmol/L in the TE-treated men, but fell by 7 +/- 0.02 nmol/L in the ND-treated men (P < 0.0001). Serum estradiol levels rose by 193.04 +/- 19.82 pmol/L in the TE-treated men although falling by 50.65 +/- 34.50 pmol/L in the ND-treated men (P < 0.0002). These data indicate that when normal men are given TE, serum IGF-I levels increase after 6 weeks of treatment. Treatment with ND did not change serum levels of IGF-I but did decrease the level of the major serum IGF-BP and therefore the level of bioavailable IGF-I may be increased in the ND group.