The male sexual cycle is regulated by a complex interplay between neuroendocrine, vascular and genital systems, and dysregulation of these systems can result in erectile dysfunction. The contributions of both vascular insufficiency and genital microstructural abnormalities to erectile dysfunction have been extensively studied, while the neuroendocrine axes have only recently come under scrutiny in the setting of male sexual function.
The aging process is associated with a decline in serum testosterone levels, which when present together with symptoms of androgen deficiency is termed late-onset hypogonadism (LOH). The true prevalence of LOH remains uncertain, although a recent report suggests that LOH is present in 3.1–7.0% of men less than 70 years old, and up to 18.4% of men over the age of 70, when using total testosterone levels of 300 ng/dl and symptomatic hypogonadism as diagnostic criteria.
Testosterone replacement in men with LOH has been shown to ameliorate the symptoms of LOH and results in improvements in erectile function without significantly increasing the incidence of clinically significant prostate cancer, although the mechanism of this improvement in erectile function remains incompletely elucidated. However, it does appear that this mechanism involves both local and central mechanisms. Growth hormone (GH) levels, like testosterone, are also known to decline in an age-dependent manner. This progressive decline has long been assumed to be physiological, although decline in GH secretion is associated with reduced lean body mass and bone density, an increased incidence of ischemic heart disease, dyslipidemia and erectile dysfunction, clinical outcomes that have also been observed in LOH.
An association between low GH levels and erectile dysfunction has been described in otherwise healthy male subjects, and recent in vitro and animal studies suggest that GH upregulates nitric oxide (NO) and may thus help to maintain erectile function. The downstream effects of growth hormone are thought to be mediated in part by insulin-like growth factors 1 and 2 (IGF-1,-2), secretion of which is upregulated by GH. Given that the half-life of IGF-1 (12–15 h) is significantly longer than that of GH (less than 20 min), IGF-1 is considered to be a superior serum marker of growth hormone secretion and activity and is therefore used as a surrogate marker for GH levels, and has been validated as an accurate marker of GH levels over time.
Studies have shown that GH and testosterone levels are closely related and that boys with delayed puberty and healthy older men with low-normal testosterone and IGF-1 have increased serum GH and IGF-1 levels with exogenous testosterone treatment. IGF-1/GH and testosterone also appear to have similar clinical effects, with IGF-1/GH reversing endothelial progenitor cell dysfunction and testosterone increasing the number of endothelial progenitor cells. Thus, it is reasonable to expect that low GH levels will correlate with sexual dysfunction, and a link between GH levels and male sexual dysfunction has been demonstrated. This study builds on the current literature and examines a relationship between IGF-1 and validated measures of patient reported sexual function, namely the Sexual Health Inventory for Men (SHIM) and the Expanded Prostate Cancer Index Composite (EPIC) questionnaires.
In this work, researchers 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 470, 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. 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. 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.
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, their 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.
Pastuszak AW, Liu JS, Vij A, et al. IGF-1 levels are significantly correlated with patient-reported measures of sexual function. Int J Impot Res2011;23(5):220-6. International Journal of Impotence Research - Abstract of article: IGF-1 levels are significantly correlated with patient-reported measures of sexual function
Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5±8.7 and 56.4±28.3?mg?ml?1, respectively. IGF-1 levels and total SHIM score correlate significantly (r=0.31, P=0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r=0.30, P=0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.
The aging process is associated with a decline in serum testosterone levels, which when present together with symptoms of androgen deficiency is termed late-onset hypogonadism (LOH). The true prevalence of LOH remains uncertain, although a recent report suggests that LOH is present in 3.1–7.0% of men less than 70 years old, and up to 18.4% of men over the age of 70, when using total testosterone levels of 300 ng/dl and symptomatic hypogonadism as diagnostic criteria.
Testosterone replacement in men with LOH has been shown to ameliorate the symptoms of LOH and results in improvements in erectile function without significantly increasing the incidence of clinically significant prostate cancer, although the mechanism of this improvement in erectile function remains incompletely elucidated. However, it does appear that this mechanism involves both local and central mechanisms. Growth hormone (GH) levels, like testosterone, are also known to decline in an age-dependent manner. This progressive decline has long been assumed to be physiological, although decline in GH secretion is associated with reduced lean body mass and bone density, an increased incidence of ischemic heart disease, dyslipidemia and erectile dysfunction, clinical outcomes that have also been observed in LOH.
An association between low GH levels and erectile dysfunction has been described in otherwise healthy male subjects, and recent in vitro and animal studies suggest that GH upregulates nitric oxide (NO) and may thus help to maintain erectile function. The downstream effects of growth hormone are thought to be mediated in part by insulin-like growth factors 1 and 2 (IGF-1,-2), secretion of which is upregulated by GH. Given that the half-life of IGF-1 (12–15 h) is significantly longer than that of GH (less than 20 min), IGF-1 is considered to be a superior serum marker of growth hormone secretion and activity and is therefore used as a surrogate marker for GH levels, and has been validated as an accurate marker of GH levels over time.
Studies have shown that GH and testosterone levels are closely related and that boys with delayed puberty and healthy older men with low-normal testosterone and IGF-1 have increased serum GH and IGF-1 levels with exogenous testosterone treatment. IGF-1/GH and testosterone also appear to have similar clinical effects, with IGF-1/GH reversing endothelial progenitor cell dysfunction and testosterone increasing the number of endothelial progenitor cells. Thus, it is reasonable to expect that low GH levels will correlate with sexual dysfunction, and a link between GH levels and male sexual dysfunction has been demonstrated. This study builds on the current literature and examines a relationship between IGF-1 and validated measures of patient reported sexual function, namely the Sexual Health Inventory for Men (SHIM) and the Expanded Prostate Cancer Index Composite (EPIC) questionnaires.
In this work, researchers 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 470, 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. 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. 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.
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, their 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.
Pastuszak AW, Liu JS, Vij A, et al. IGF-1 levels are significantly correlated with patient-reported measures of sexual function. Int J Impot Res2011;23(5):220-6. International Journal of Impotence Research - Abstract of article: IGF-1 levels are significantly correlated with patient-reported measures of sexual function
Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5±8.7 and 56.4±28.3?mg?ml?1, respectively. IGF-1 levels and total SHIM score correlate significantly (r=0.31, P=0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r=0.30, P=0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.
