IGF-1, Testosterone and Cancer

[Holden]

Hi All - just trying to be an informed consumer and manager of my health here. What is the prevailing wisdom on the following two correlations and in some cases causations, depending on which study / article you read:

1) Higher IGF-1 levels in older adults can increase the risk of cancer

2) Exogenous testosterone increases IGF-1

Thanks!

-H

 

[Vince]

This only my opinion, TRT did not raise my IGF-1. My last labs showed my levels to be 66 mg/mL. I did use sermorlin to raise my level but felt no difference and I didn't like injecting sermonlin. So I stopped.
The studies about increase of cancer at higher IGF-1 levels may be true, but how much of an increase?

 

[Holden]

Thanks for Sharing Vince. The articles I've read say higher than 175.

My experience on my previous cycle was pre-exogenous testosterone my Total T=420 and IGF-1 was 160, then midway through on the same test where my Total T was 1020, my IGF-1 was 225 (on Labcorp's range 67-205). That's why I'm checking on what the current understanding and research shows.

 

[Guided_by_Voices]

From what I've read, ( I don't remember all the sources but I believe suppversity has a good compilation) what you really don't want is low IGF-1, and high is not great either, so it is the typical u-shaped curve. TRT is more likely to raise you out of a low range than create a problematically high number. Also, it would be easy to create a very long list of anti-cancer strategies that are more important than IGF-1, such as avoiding chronically elevated insulin, getting frequent moderate amounts of mid-day sun exposure, and on and on

 

[Holden]

From what I've read, ( I don't remember all the sources but I believe suppversity has a good compilation) what you really don't want is low IGF-1, and high is not great either, so it is the typical u-shaped curve. TRT is more likely to raise you out of a low range than create a problematically high number. Also, it would be easy to create a very long list of anti-cancer strategies that are more important than IGF-1, such as avoiding chronically elevated insulin, getting frequent moderate amounts of mid-day sun exposure, and on and on

Thanks for that input, Guided.

 

[captain]

I had a Urologist tell me that this is why you see more prostate cancer in people with Diabetes. The release of Insulin and GH come together and was in his opinion the cause. The same Urologist said a total testosterone of 200 is all you need so what he says don't mean much to me.

 

[lenny]

At no point during my four years on TRT have I seen evidence of exogenous testosterone raising my IGF-1.

In fact, it's actually fallen while I've been on TRT, but that could be due to my plant-based diet. In the past three years since I went plant-based, it's slowly fallen from 347 ng/ml to 175 ng/ml.

 

[Holden]

I had a Urologist tell me that this is why you see more prostate cancer in people with Diabetes. The release of Insulin and GH come together and was in his opinion the cause. The same Urologist said a total testosterone of 200 is all you need so what he says don't mean much to me.

Thanks for sharing captain!

 

[Holden]

At no point during my four years on TRT have I seen evidence of exogenous testosterone raising my IGF-1.

In fact, it's actually fallen while I've been on TRT, but that could be due to my plant-based diet. In the past three years since I went plant-based, it's slowly fallen from 347 ng/ml to 175 ng/ml.

Thanks for sharing lenny! Curious if you're open to sharing, how did you have a 347 reading for IGF-1 to begin with, it seems kind of high, were you on exogenous testosterone and/or sermorelin at anytime prior to going plant based diet? Or just eating a lot of meat

 

[lenny]

Thanks for sharing lenny! Curious if you're open to sharing, how did you have a 347 reading for IGF-1 to begin with, it seems kind of high, were you on exogenous testosterone and/or sermorelin at anytime prior to going plant based diet? Or just eating a lot of meat

That's the thing, I don't know why it was so high! I never did TRT before, and I never even heard of sermorelin before I read this thread. That high IGF-1 was actually one of the reasons I decided to stop eating meat, but I really wasn't eating an unusual amount of it before. So it's a kind of a mystery. Needless to say I was happy to see it finally fall within a normal range.

 

[Nelson Vergel]

Long term studies in children who used growth hormone for years to increase height showed no increased risk of cancers. Growth hormone increases IGF-1. Here are a few references:

Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns
The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy—A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee

 

[Nelson Vergel]

Dose was a little high.

J Clin Endocrinol Metab. 1993 Sep;77(3):776-9.

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.

 

[Will Brink]

Hi All - just trying to be an informed consumer and manager of my health here. What is the prevailing wisdom on the following two correlations and in some cases causations, depending on which study / article you read:

1) Higher IGF-1 levels in older adults can increase the risk of cancer

2) Exogenous testosterone increases IGF-1

Thanks!

-H

Covered extensively here:

"While the IGF-1 system undoubtedly plays an important role in cancer development and progression, lower IGF-1 levels also increase cancer risk. Thus, the relation between IGF-1 and cancer mortality is U-shaped, as is the relation between IGF-1 and all-cause mortality. It should be underscored that only low IGF-1 levels seem to be associated with increased cardiovascular mortality, and that the risk of high IGF-1 levels only pertains to cancer mortality (and not cardiovascular mortality)."

Cont:

http://www.brinkzone.com/general-health/whats-the-relation-between-igf-1-and-cancer/

 

[Holden]

Long term studies in children who used growth hormone for years to increase height showed no increased risk of cancers. Growth hormone increases IGF-1. Here are a few references:

Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns


The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke



Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy—A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee

Thanks Nelson! Yes, I've read too that the kids are alright.

 

[Holden]

Dose was a little high.

J Clin Endocrinol Metab. 1993 Sep;77(3):776-9.

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.

Thanks Nelson! This seems to align with what I've seen, that in some cases there is an indeed a correlation. However it hasn't been clear how long elevated IGF-1 levels remain, even with continued exogenous Testosterone administration. Does this study give any indication or was the IGF-1 reading just the one time after 6 weeks?

 

[Will Brink]

Thanks Nelson! This seems to align with what I've seen, that in some cases there is an indeed a correlation. However it hasn't been clear how long elevated IGF-1 levels remain, even with continued exogenous Testosterone administration. Does this study give any indication or was the IGF-1 reading just the one time after 6 weeks?

Low IGF-1 also associated with increased cancer and low IGF-1 strongly correlated to CVD.

 

[Nelson Vergel]

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



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&#8211;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.

 

[MikeXL]

W

Will, thanks for sharing. I always get concerned about these epidemiological studies because of the confounding factors. Here is an old epidemiological joke I heard from Bruce Ames - "Miami, it's a funny place. The people there are born Latino and die Jewish".

What is your sense on whether it could be that disease states or a state that predisposes one to cancer or CVD could be the causation behind the association between low IGF values and increased risk of cancer and CVD? Thanks

Low IGF-1 also associated with increased cancer and low IGF-1 strongly correlated to CVD.

 

[Will Brink]

W

Will, thanks for sharing. I always get concerned about these epidemiological studies because of the confounding factors. Here is an old epidemiological joke I heard from Bruce Ames - "Miami, it's a funny place. The people there are born Latino and die Jewish".

What is your sense on whether it could be that disease states or a state that predisposes one to cancer or CVD could be the causation behind the association between low IGF values and increased risk of cancer and CVD? Thanks

As you say, always hard to know cause and effect with epi/correlational studies. One has to look at each study to see what confounders they controlled for, size effects, and the shear number of studies finding an effect. Of course they can't do direct intervention studies with that type of thing in humans, so pretty much left with epi/correlational stuff, and then look at if mechanistic studies and such support it. The data that finds low IGF-1 associated to CVD is extensive enough in my view that keeping IGF-1 in range seems warranted.

 

[MikeXL]

Thanks!!!!

As you say, always hard to know cause and effect with epi/correlational studies. One has to look at each study to see what confounders they controlled for, size effects, and the shear number of studies finding an effect. Of course they can't do direct intervention studies with that type of thing in humans, so pretty much left with epi/correlational stuff, and then look at if mechanistic studies and such support it. The data that finds low IGF-1 associated to CVD is extensive enough in my view that keeping IGF-1 in range seems warranted.