and EPIC questionnaires after a diagnosis of prostate

cancer had been made. Given the psychologically

stressful nature of a cancer diagnosis, this may have

resulted in lower SHIM and EPIC scores. However,

given that all men in the study carried the diagnosis

of prostate cancer, a uniform reduction in ques-

tionnaire scores would be expected, a possibility we

cannot evaluate given the lack of pre-diagnosis

questionnaire responses.

Erectile dysfunction is a known early predictor of

coronary artery disease. Deficiency of GH or IGF-1

has been implicated in the pathogenesis of cardio-

vascular disease and atherosclerosis and is asso-

ciated with an increased prevalence of ischemic

heart disease.

16,17

GH/IGF-1 deficiency is thought

contribute

endothelial

dysfunction,

and

low GH/IGF-1 levels have been correlated with a

decreased number and diminished function of

endothelial progenitor cells, which function in

vascular repair.

Notably, this endothelial progeni-

tor cell dysfunction is reversible with GH adminis-

tration, which suggests a possible role for GH in the

treatment of vascular disorders, including erectile

dysfunction.

GH and IGF-1 have also been shown

to have antioxidant and anti-inflammatory effects in

animal models, suggesting a protective role for GH/

IGF-1 in vascular disease given the role of oxidative

stress in initiating lipid-lesion formation as well as

in the destabilization and progression of these

lesions.

Interestingly, our data link IGF-1 levels

to hyperlipidemia, highlighting a potential inter-

play between serum lipids and GH/IGF-1 levels.

Although it is tempting to hypothesize that this

correlation may indicate a response by the GH axis

to hyperlipidemia, additional analysis is necessary

to fully elucidate this.

GH has been shown to modulate the NO/cyclic

guanosine monophosphate signaling pathways and

aid in the restoration of cavernosal smooth muscle

integrity in rats.

GH levels increase during sexual

arousal and GH has been shown to induce relaxation

of smooth muscle in a dose-dependent manner and

upregulate NO and cyclic guanosine monophos-

phate serum levels in human corpus caverno-

sum.

20,29

GH has also been shown to have a trophic

effect on neuronal and endothelial nitric oxide

synthase- (nNOS and eNOS, respectively) contain-

ing neurons after cavernous neurotomy in rats,

suggesting that GH may be important in the

maintenance or restoration of erectile function

post-prostatectomy.

Like, GH, IGF-1 has growth-

stimulating effects and is thought to improve

erectile function in diabetic rats as measured by

maximum intracavernosal pressure as well as the

maximal intracavernosal pressure to mean arterial

pressure ratio.

22,37

Together these data support a role

for GH and IGF-1 in sexual arousal and erectile

function, and indicate that GH and IGF-1 may func-

tion using a well-established pathway for erectile

stimulation.

A relationship between GH, IGF-1 and testo-

sterone

has

previously

been

demonstrated.

1,2

Curiously, no significant correlation is demonstrated

between serum IGF-1 and testosterone levels or

between testosterone levels and SHIM/EPIC scores

in our work. However, we have observed this

correlation to be lacking in patients seen in our

practice that were not included in this study, and

suspected that this finding may be related to the use

of exogenous testosterone by patients before pre-

sentation to our clinic, which would affect serum

testosterone levels and could affect the relationship

between testosterone and IGF-1.

In light of our findings linking the GH axis to

sexual dysfunction, it is conceivable that supple-

mentation with GH or IGF-1 could improve recovery

of erectile function after radical prostatectomy.

However, there is concern regarding a possible role

for GH, IGFs and IGF-binding proteins (IGFBPs) in

the development of prostate cancer and stimulation

of its growth.

GH has been shown to stimulate

prostate cancer cell growth and both GH and the

GH receptor is expressed in prostate cancer cells,

suggesting a potential auto- or paracrine pathway

for stimulating growth.

Elevated IGF-1 levels, as

well as low IGFBP3 levels, were recently shown

to correlate with an up to 21% increased risk of

prostate cancer, and an increased risk of prostate

cancer has been demonstrated in Latin men with

elevated IGF-1 levels, results that have been echoed

in other cohorts.

39–41

These data argue for caution

when considering supplementation with GH or

IGF-1 in men with erectile dysfunction.

In this study, we found no correlation between

Gleason score and IGF-1 levels. Although this does

not suggest that GH does not stimulate prostate

cancer cell growth, the data argue that the GH axis

does not stimulate development of more aggressive

tumors. However, whether men being treated with

GH have an increased risk of prostate cancer and

whether exogenous GH administration affects tumor

severity cannot be addressed. Further work defining

the mechanisms of function of GH and IGF-1 in

prostate cells should be undertaken and the risks

of carcinogenesis should be more clearly defined.

In addition to the lack of correlation between serum

IGF-1 levels and Gleason score, no significant

correlation was identified between serum testo-

sterone levels and Gleason score. Although a link

between serum testosterone levels and prostate

cancer severity has been demonstrated, previous

studies have focused on Gleason scores

8 and

found an increased risk of more aggressive prostate

cancer only in men

65 years old.

In our ana-

lysis, only four patients had Gleason score 8 or

higher cancer and only one of these was more than

65 years old, which may explain a lack of correlation

between serum testosterone level and Gleason score

given the predominance of Gleason score 6 and 7

prostate cancer within our cohort. However, in a

IGF-1 levels correlate with sexual dysfunction

AW Pastuszak

et al

224

International Journal of Impotence Research