Prognostic utility of erectile dysfunction for cardiovascular disease in younger men and those with diabetes.

Multiple published studies have established erectile dysfunction (ED) as an independent risk marker for cardiovascular disease (CVD). In fact, incident ED has a similar or greater predictive value for cardiovascular events than traditional risk factors including smoking, hyperlipidemia, and family history of myocardial infarction. Here, we review evidence that supports ED as a particularly significant harbinger of CVD in 2 populations: men <60 years of age and those with diabetes. Although addition of ED to the Framingham Risk Score only modestly improved the 10-year predictive capacity of the Framingham Risk Score for myocardial infarction or coronary death data in men enrolled in the Massachusetts Male Aging Study, other epidemiologic studies suggest that the predictive value of ED is quite strong in younger men. Indeed, in the Olmstead County Study, men 40 to 49 years of age with ED had a 50-fold higher incidence of new-incident coronary artery disease than those without ED. However, ED had less predictive value (5-fold increased risk) for coronary artery disease in men 70 years and older. Several studies, including a large analysis of more than 6300 men enrolled in the ADVANCE study, suggest that ED is a particularly powerful predictor of CVD in diabetic men as well. Based on the literature reviewed here, we encourage physicians to inquire about ED symptoms in all men more than 30 years of age with cardiovascular risk factors. Identification of ED, particularly in men <60 years old and those with diabetes, represents an important first step toward CVD risk detection and reduction.

Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span.

Disruption of the insulin/IGF-I pathway increases life span in invertebrates. However, effects of decreased IGF-I signaling in mammalian models remain controversial. Using a rodent model with a specific and limited deficiency of GH and IGF-I, we report that GH and IGF-I deficiency throughout life [GH deficiency (GHD)] has no effect on life span compared with normal, heterozygous animals. However, treatment of GHD animals with GH from 4-14 wk of age [adult-onset (AO) GHD] increased median and maximal life span by 14% and 12%, respectively. Analysis of end-of-life pathology indicated that deficiency of these hormones decreased tumor incidence in GHD and AO-GHD animals (18 and 30%, respectively) compared with heterozygous animals and decreased the severity of, and eliminated deaths from, chronic nephropathy. Total disease burden was reduced by 24% in GHD and 16% in AO-GHD animals. Interestingly, the incidence of intracranial hemorrhage increased by 154 and 198% in GHD and AO-GHD animals, respectively, compared with heterozygous animals. Deaths from intracranial hemorrhage in AO-GHD animals were delayed by 14 wk accounting for the increased life span compared with GHD animals. The presence of GH and IGF-I was necessary to maximize reproductive fitness and growth of offspring early in life and to maintain cognitive function and prevent cartilage degeneration later in life. The diverse effects of GH and IGF-I are consistent with a model of antagonistic pleiotropy and suggest that, in response to a deficiency of these hormones, increased life span is derived at the risk of functional impairments and tissue degeneration.

Growth hormone-deficient dwarf animals are resistant to dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis.

Increased plasma IGF-1 has consistently been associated with a variety of human cancers, whereas reduced levels of IGF-1 are associated with increased lifespan in other species. However, the aforementioned relationships are correlational or are derived from animal models that are not specific for growth hormone/IGF-1 excess or deficiency. This study was designed to assess the effects of physiological changes in growth hormone and IGF-1 expression on dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis. At 50 days of age, female heterozygous (dw/+) and growth hormone deficient dwarf (dw/dw) rats of the Lewis strain received a single dose of DMBA (80 micro g/g of body weight) via oral gavage. Animals were assigned to one of four experimental groups: a) heterozygous animals (normal size), b) dwarf animals administered vehicle, c) dwarf animals administered low levels of porcine growth hormone (50 micro g twice daily), and d) dwarf animals administered high levels of porcine growth hormone (200 micro g twice daily). At study termination, heterozygous animals exhibited a 70% incidence of mammary tumors, whereas no tumors were observed in saline-treated dwarf animals. Administration of either 100 micro g or 400 micro g growth hormone/day resulted in a dose dependent increase in incidence of mammary tumors (83 and 100%, respectively). Furthermore, heterozygous animals exhibited 1.5 +/- 0.25 tumors per tumor-bearing animal, whereas dwarf animals administered 100 micro g and 400 micro g growth hormone per day had 1.9 +/- 0.63 and 3.4 +/- 0.83 tumors per animal, respectively. The present study demonstrates that DMBA-induced carcinogenesis is dependent on critical plasma levels of growth hormone and IGF-1, and that growth hormone/IGF-1 deficient animals are resistant to DMBA-induced carcinogenesis.