IGF-1 Levels and Sexual Function: Part 2 of 2

IGF-1 LEVELS AND SEXUAL FUNCTION: PART 2 OF 2


.....continued from Part 1.......

Subjects' IGF-1 levels were also correlated with self-reported sexual function as assessed using the sexual and hormonal domains of the EPIC questionnaire. The median±s.d. score of the sexual domain of the EPIC questionnaire was 56.4±28.3 (range 6.3–96.2) (). Similar to the findings with SHIM score, there was a significant correlation between the sexual domain of the EPIC questionnaire and IGF-1 levels for all ages ( r=0.30, P=0.02) (, Figure 2). In contrast, there was no correlation between the sexual domain of the EPIC questionnaire and IGF-1 levels for any single age group, although the correlation within the >70-year-old age group approached significance ( r=0.87, P=0.06). In addition, no significant correlation was found between testosterone level and SHIM or EPIC score, which supports previous findings in the literature. [SUP][32][/SUP] In addition, there was no correlation between the hormonal domain of the EPIC questionnaire and either IGF-1 or testosterone levels.
Table 1. Patient characteristics

Abbreviations: BMI, body mass index; ED, erectile dysfunction; EPIC, Expanded Prostate Cancer Index Composite; IGF-1, insulin-like growth factor 1; RP, radical prostatectomy; SHIM, Sexual Health Inventory for Men; TRT, testosterone replacement therapy.

Table 2. Spearman's correlation coefficients between IGF-1 and SHIM/EPIC scores, IGF-1 and testosterone, by age

Abbreviations: IGF-1, insulin-like growth factor 1; EPIC, Expanded Prostate Cancer Index Composite; SHIM, Sexual Health Inventory for Men. 'R' represents the Spearman's correlation coefficient. 'EPIC sex' refers to the sexual domain portion of the EPIC questionnaire, whereas 'EPIC horm' refers to the hormonal domain. SHIM 1—SHIM 5 refer to individual questions of the SHIM questionnaire.



Figure 2.
Total Expanded Prostate Cancer Index Composite (EPIC) sexual domain score vs serum insulin-like growth factor 1 (IGF-1) Level. All subjects' IGF-1 level plotted against their self-reported scores of sexual function based on the sexual domain portion of the EPIC questionnaire. There is a statistically significant correlation between the two measured values (Spearman's correlation coefficient, r=0.30; P=0.02).



To control for the impact of comorbidities on IGF-1 levels, multivariate analysis using linear regression modeling was carried out. These data demonstrated that only hyperlipidemia is predictive of IGF-1 levels ( P=0.02, ), with other comorbidities not significantly impacting IGF-1 levels. The prevalence of hyperlipidemia in our subject population as a function of age revealed no significant difference, suggesting that the presence of hyperlipidemia does not affect the findings described above.
Table 3. Multivariate analysis assessing IGF-1 levels, age and comorbidities

Abbreviation: IGF-1, insulin-like growth factor 1

In light of reports suggesting that elevated IGF-1 and GH levels stimulate prostate cancer cell growth, we determined the Spearman's rank correlation between IGF-1 level and both total Gleason score, as well as the high component of the Gleason score. Our data demonstrate no significant correlation between IGF-1 levels and Gleason score, suggesting that while GH and IGF-1 may stimulate the growth of prostate cancer, tumor severity is not affected in this group of men scheduled for radical prostatectomy. In addition, no correlation was shown between testosterone level and Gleason score for all ages or in any age group (data not shown).
Discussion

The prevalence of LOH is likely to continue increasing as the world's population ages. Recent work has established a role for testosterone in the development and maintenance of erections, and testosterone replacement has been shown to ameliorate the symptoms of LOH, including erectile dysfunction. [SUP][33–35][/SUP] In contrast, the role of GH in the maintenance of sexual function is less well established, although studies have shown a relationship between GH and erectile function.
In this work, we demonstrate a statistically significant correlation between self-reported, validated measures of sexual function in men, the SHIM and EPIC questionnaires, and IGF-1 levels, most robustly in men >70, as well as in men between 50 and 59 years old. In contrast, a correlation between testosterone levels and SHIM/EPIC scores is not demonstrated. Notably, study subjects were given SHIM 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 questionnaire 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 cardiovascular disease and atherosclerosis and is associated with an increased prevalence of ischemic heart disease. [SUP][16,17][/SUP] GH/IGF-1 deficiency is thought to contribute to 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. [SUP][27][/SUP] Notably, this endothelial progenitor cell dysfunction is reversible with GH administration, which suggests a possible role for GH in the treatment of vascular disorders, including erectile dysfunction. [SUP][27][/SUP] 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. [SUP][36][/SUP] Interestingly, our data link IGF-1 levels to hyperlipidemia, highlighting a potential interplay 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. [SUP][24][/SUP] 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 monophosphate serum levels in human corpus cavernosum. [SUP][20,29][/SUP] GH has also been shown to have a trophic effect on neuronal and endothelial nitric oxide synthase- (nNOS and eNOS, respectively) containing neurons after cavernous neurotomy in rats, suggesting that GH may be important in the maintenance or restoration of erectile function post-prostatectomy. [SUP][23][/SUP] 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. [SUP][22,37][/SUP] 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 function using a well-established pathway for erectile stimulation.
A relationship between GH, IGF-1 and testosterone has previously been demonstrated. [SUP][1,2][/SUP] 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 presentation 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 supplementation 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. [SUP][26][/SUP] 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. [SUP][38][/SUP] 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. [SUP][39–41][/SUP] 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 testosterone 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. [SUP][42][/SUP] In our analysis, 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 recent study of 478 men screened for prostate cancer with transrectal ultrasound-guided biopsy, no relationship was observed between serum testosterone level and prostate cancer severity. [SUP][43][/SUP] Thus, it is possible that the relationship between testosterone level and Gleason score is indeed most significant in older men with more aggressive tumors.
Our study was limited by several factors. First, the study was performed with a cohort of men diagnosed with prostate cancer. Although the considerations for questionnaire score are addressed above, it is also possible that unaccounted for factors, including individual differences in anxiety levels before major surgery or as a result of the cancer diagnosis, may have affected both IGF-1 levels and erectile function. Second, most of the correlations, save for those in the >70-year-old age group, are fairly low. Although this could be a result of the factors above, there may be additional variables that affect the relationship between the GH axis and sexual function and are currently unaccounted for.
Considering the overlap between GH and testosterone in the pathogenesis of erectile dysfunction, it may be beneficial to evaluate both the testosterone and GH axes when evaluating etiology and considering the treatment of erectile dysfunction. Our results support a relationship between IGF-1 and male sexual function, and strengthen the argument to more closely study the role of IGF-1 in erectile dysfunction. There do not exist sufficient data to use IGF-1 or GH supplementation in men with erectile dysfunction currently, and studies demonstrating a role of GH and IGF-1 in development and progression of prostate cancer may further temper this possibility. However, recent studies, including ours, show potential and promise for new ways to enhance current treatment protocols that could improve quality of life in men with erectile dysfunction.
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It took me forever to surmise this from the article: IGF-1 Very very good! lmao


Our results support a relationship between IGF-1 and male sexual function, and strengthen the argument to more closely study the role of IGF-1 in erectile dysfunction. There do not exist sufficient data to use IGF-1 or GH supplementation in men with erectile dysfunction currently, and studies demonstrating a role of GH and IGF-1 in development and progression of prostate cancer may further temper this possibility. However, recent studies, including ours, show potential and promise for new ways to enhance current treatment protocols that could improve quality of life in men with erectile dysfunction.

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More to come from work tonight....Finding lots from my continuing ed sites...