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The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction
Department of Biochemistry and Urology, Boston University School of Medicine, Boston, MA 02118, USA. [email protected]
The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. These factors increase the risk of cardiovascular disease (CVD) and/or type 2 diabetes. Although the etiology of this syndrome is thought to stem from obesity and physical inactivity, the extent of interactions of the individual MetS components with one another remains poorly defined. Obesity, diabetes, hypogonadism, and specific hormone and metabolic profiles have been implicated in the pathophysiology of CVD. The evolving role of androgens in MetS and CVD is of paramount importance. Reduced androgen levels associated with hypogonadism or androgen deprivation therapy increase cardiovascular risk factors and produce marked adverse effects on cardiovascular function. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. It is suggested that MetS, diabetes, and CVD will increase in the upcoming decades. Thus, it is critically important to develop a better understanding of how obesity, diabetes and hypogonadism contribute to androgen deficiency and the various pathophysiologic states of vascular disease. In this review we discuss the current literature pertaining to androgen deficiency, MetS, and ED, because the relationship of these factors is of scientific and clinical importance. Specifically, we will focus on exploring the relationships between hypogonadism, obesity, MetS, and ED.
Department of Biochemistry and Urology, Boston University School of Medicine, Boston, MA 02118, USA. [email protected]
The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. These factors increase the risk of cardiovascular disease (CVD) and/or type 2 diabetes. Although the etiology of this syndrome is thought to stem from obesity and physical inactivity, the extent of interactions of the individual MetS components with one another remains poorly defined. Obesity, diabetes, hypogonadism, and specific hormone and metabolic profiles have been implicated in the pathophysiology of CVD. The evolving role of androgens in MetS and CVD is of paramount importance. Reduced androgen levels associated with hypogonadism or androgen deprivation therapy increase cardiovascular risk factors and produce marked adverse effects on cardiovascular function. MetS has been associated with hypogonadism and erectile dysfunction (ED), and MetS may be considered a risk factor for ED. It is suggested that MetS, diabetes, and CVD will increase in the upcoming decades. Thus, it is critically important to develop a better understanding of how obesity, diabetes and hypogonadism contribute to androgen deficiency and the various pathophysiologic states of vascular disease. In this review we discuss the current literature pertaining to androgen deficiency, MetS, and ED, because the relationship of these factors is of scientific and clinical importance. Specifically, we will focus on exploring the relationships between hypogonadism, obesity, MetS, and ED.
The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance.
Department of Biochemistry and Urology, Boston University School of Medicine, Boston, MA 02118, USA. [email protected]
A considerable body of evidence exists suggesting a link among reduced testosterone plasma levels, type 2 diabetes (T2D), and insulin resistance (IR). Hypogonadal men are at higher risk for T2D. Here we evaluate the relationships between testosterone, metabolic syndrome (MetS), T2D, and IR and discuss the relationships among androgen deficiency and these factors, especially as it ultimately relates to the development of cardiovascular disease and erectile dysfunction (ED). Thus, a comprehensive literature search was carried out using PubMed, and relevant articles pertinent to androgen deficiency, T2D, IR, MetS, and ED were reviewed and discussed. Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Treatment of prostate cancer patients with surgical or medical castration exacerbates IR and glycemic control, strengthening the link between testosterone deficiency and onset of T2D and IR. Androgen therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels. We suggest that androgen deficiency is associated with IR, T2D, MetS, and with increased deposition of visceral fat, which serves as an endocrine organ, producing inflammatory cytokines and thus promoting endothelial dysfunction and vascular disease.
Department of Biochemistry and Urology, Boston University School of Medicine, Boston, MA 02118, USA. [email protected]
A considerable body of evidence exists suggesting a link among reduced testosterone plasma levels, type 2 diabetes (T2D), and insulin resistance (IR). Hypogonadal men are at higher risk for T2D. Here we evaluate the relationships between testosterone, metabolic syndrome (MetS), T2D, and IR and discuss the relationships among androgen deficiency and these factors, especially as it ultimately relates to the development of cardiovascular disease and erectile dysfunction (ED). Thus, a comprehensive literature search was carried out using PubMed, and relevant articles pertinent to androgen deficiency, T2D, IR, MetS, and ED were reviewed and discussed. Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Treatment of prostate cancer patients with surgical or medical castration exacerbates IR and glycemic control, strengthening the link between testosterone deficiency and onset of T2D and IR. Androgen therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels. We suggest that androgen deficiency is associated with IR, T2D, MetS, and with increased deposition of visceral fat, which serves as an endocrine organ, producing inflammatory cytokines and thus promoting endothelial dysfunction and vascular disease.
The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease.
A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset and/or progression of cardiovascular disease (CVD). It is our objective to evaluate the relationships between Testosterone (T) deficiency and risk factors of cardiovascular disease (CVD) and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. The relationship between androgen deficiency and endothelial function, lipid profiles, inflammatory responses, altered smooth muscle and hypertension are discussed with regard to CVD. A comprehensive literature search was carried out using Pub Med from 1980 through 2008 and relevant articles pertinent to androgen deficiency and vascular disease were evaluated and discussed. Low testosterone, whether attributed to hypogonadism or androgen deprivation therapy (ADT), in men with prostate carcinoma, produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low density lipoprotein (LDL), increased production of pro-inflammatory factors, increases thickness of the arterial wall, and contributes to endothelial dysfunction. T supplementation restores arterial vasoreactivity, reduces pro-inflammatory cytokines, total cholesterol, and triglyceride levels and improves endothelial function, but may also reduce high density lipoprotein (HDL) levels. In conclusion, T is an anabolic hormone with a wide range of beneficial effects on men's health. The therapeutic role of T in men's health, however, remains a hotly debated issue for a number of reasons, including the purported risk of prostate cancer. In view of the emerging evidence suggesting that androgen deficiency is a risk factor for CVD, androgen replacement therapy may potentially reduce CVD risk in hypogonadal men. It should be emphasized, however, that androgen replacement therapy should be done with very thorough and careful monitoring for prostate diseases.
A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset and/or progression of cardiovascular disease (CVD). It is our objective to evaluate the relationships between Testosterone (T) deficiency and risk factors of cardiovascular disease (CVD) and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. The relationship between androgen deficiency and endothelial function, lipid profiles, inflammatory responses, altered smooth muscle and hypertension are discussed with regard to CVD. A comprehensive literature search was carried out using Pub Med from 1980 through 2008 and relevant articles pertinent to androgen deficiency and vascular disease were evaluated and discussed. Low testosterone, whether attributed to hypogonadism or androgen deprivation therapy (ADT), in men with prostate carcinoma, produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low density lipoprotein (LDL), increased production of pro-inflammatory factors, increases thickness of the arterial wall, and contributes to endothelial dysfunction. T supplementation restores arterial vasoreactivity, reduces pro-inflammatory cytokines, total cholesterol, and triglyceride levels and improves endothelial function, but may also reduce high density lipoprotein (HDL) levels. In conclusion, T is an anabolic hormone with a wide range of beneficial effects on men's health. The therapeutic role of T in men's health, however, remains a hotly debated issue for a number of reasons, including the purported risk of prostate cancer. In view of the emerging evidence suggesting that androgen deficiency is a risk factor for CVD, androgen replacement therapy may potentially reduce CVD risk in hypogonadal men. It should be emphasized, however, that androgen replacement therapy should be done with very thorough and careful monitoring for prostate diseases.
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