The incidence of erectile dysfunction (ED) increases with age and cardiovascular disease risk factors, such as hypertension, hyperlipidemia, insulin resistance, obesity, and diabetes. These risk factors are thought to contribute to endothelial dysfunction and atherosclerosis, thus contributing to the pathophysiology of ED. The role of the endothelium in regulating erectile physiology is well established. However, the role of androgens in modulating endothelial function and endothelial repair mechanisms subsequent to vascular injury in erectile tissue remains a subject of intensive research. The clinical and preclinical evidence discussed in this review suggests that androgens regulate endothelial function and also play an important role in the development and maturation of endothelial progenitor cells (EPCs), which are thought to play a critical role in repair of endothelial injury in vascular beds. In this review, we discuss the data available on the effects of androgens on endothelial function and EPCs in the repair of vascular injury. Indeed, more research is needed to fully understand the molecular and cellular basis of androgen action in regulating the development, differentiation, maturation, migration, and homing of EPCs to the site of injury. A better understanding of these processes will be critical to the development of new therapeutic approaches to the treatment of vascular ED.
Androgens* ; Atherosclerosis ; Cardiovascular Diseases ; Endothelial Cells ; Endothelium ; Erectile Dysfunction ; Hyperlipidemias ; Hypertension ; Incidence ; Insulin Resistance ; Male ; Nitric Oxide ; Obesity ; Risk Factors ; Stem Cells* ; Testosterone ; Vascular System Injuries

Lower urinary tract function is modulated by neural, vascular and urethral and bladder structural elements. The pathophysiological mechanisms of lower urinary tract symptoms (LUTS) encompass prostate enlargement, alterations in urethra histological structure bladder fibrosis and alterations in pelvic neuronal and vascular networks, The complex pathophysiological relationship between testosterone (T) deficiency (TD) and the constellations LUTS, and metabolic dysfunction manifested in the metabolic syndrome (Met S) remains poorly understood. TD has emerged as one the potential targets by which Met S may contribute to the onset and development as well as worsening of LUTS. Because it has been recognized that treatment of men with Met S with T therapy ameliorates Met S components, it is postulated that T therapy may represent a therapeutic target in improving LUTS. Furthermore, the effect of TD on the prostate remains unclear, and often debatable. It is believed that T exclusively promotes prostate growth, however recent evidence has strongly contradicted this belief. The true relationship between benign prostatic hyperplasia, TD, and LUTS remains elusive and further research will be required to clarify the role of T in both benign prostatic hypertrophy (BPH) and LUTS as a whole. Although there is conflicting evidence about the benefits of T therapy in men with BPH and LUTS, the current body of literature supports the safety of using this therapy in men with enlarged prostate. As the population afflicted with obesity epidemic continues to age, the number of men suffering from Met S and LUTS together is expected to increase.
Fibrosis ; Humans ; Hypogonadism ; Lower Urinary Tract Symptoms* ; Male ; Neurons ; Obesity ; Prostate ; Prostatic Hyperplasia ; Testosterone* ; Urethra ; Urinary Bladder ; Urinary Tract

With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms (LUTS). Because the prostate is an androgen target tissue, and transforms testosterone into 5alpha-dihydrotestosterone (5alpha-DHT), a potent androgen, via 5alpha-reductase (5alpha-R) activity, inhibiting this key metabolic reaction was identified as a target for drug development to treat symptoms of BPH. Two drugs, namely finasteride and dutasteride were developed as specific 5alpha-reductase inhibitors (5alpha-RIs) and were approved by the U.S. Food and Drug Administration for the treatment of BPH symptoms. These agents have proven useful in the reducing urinary retention and minimizing surgical intervention in patients with BPH symptoms and considerable literature exists describing the benefits of these agents. In this review we highlight the adverse side effects of 5alpha-RIs on sexual function, high grade prostate cancer incidence, central nervous system function and on depression. 5alpha-Rs isoforms (types 1-3) are widely distributed in many tissues including the central nervous system and inhibition of these enzymes results in blockade of synthesis of several key hormones and neuro-active steroids leading to a host of adverse effects, including loss of or reduced libido, erectile dysfunction, orgasmic dysfunction, increased high Gleason grade prostate cancer, observed heart failure and cardiovascular events in clinical trials, and depression. Considerable evidence exists from preclinical and clinical studies, which point to significant and serious adverse effects of 5alpha-RIs, finasteride and dutasteride, on sexual health, vascular health, psychological health and the overall quality of life. Physicians need to be aware of such potential adverse effects and communicate such information to their patients prior to commencing 5alpha-RIs therapy.
Aging ; Central Nervous System ; Depression* ; Erectile Dysfunction ; Finasteride ; Heart Failure ; Humans ; Hyperplasia ; Incidence ; Libido ; Lower Urinary Tract Symptoms ; Male ; Orgasm ; Prostate ; Prostatic Neoplasms* ; Protein Isoforms ; Quality of Life ; Reproductive Health ; Sexual Dysfunction, Physiological ; Steroids ; Testosterone ; United States Food and Drug Administration ; Urinary Retention

PURPOSE: Diabetes profoundly and negatively impacts all domains of female sexual function, however, the underlying pathophysiological mechanisms remain unknown. To date, limited studies have been published on the effects of type 1 & type 2 diabetes on female genital sexual arousal and how this may impact overall sexual function. The aim of this review is to discuss the effects of diabetes on female sexual function and insights from laboratory studies on the underlying pathophysiology. MATERIALS AND METHODS: Using PubMed, we reviewed and evaluated the literature published between 1970 and 2009 and data from our laboratories and others investigating the effects of type 1 and type 2 diabetes on genital sexual arousal responses. RESULTS: Women with diabetes experience diminished genital arousal, reduced vaginal lubrication, vaginal atrophy, dyspareunia, and increased vaginal infections. Also, a number of studies using type 1 and type 2 diabetic animal models have reported reduced plasma estradiol levels and marked physiological, biochemical and histological changes in genital tissues. In animal studies, diabetes alters genital tissue structure and attenuates expression of the estrogen, progesterone and androgen receptors and alters vaginal and clitoral hemodynamics. Importantly, treatment of diabetic animals with estradiol in the face of persistent hyperglycemia can restore vaginal structure and sex steroid receptor expression. CONCLUSIONS: Type 1 & type 2 diabetic complications produce significant structural and functional disruptions in genital organs and attenuate genital hemodynamics. In the type 2 animal model, estradiol treatment ameliorates diabetic-induced pathophysiological alterations in genital tissues, such as the vagina. This suggests that estrogen supplementation may be beneficial in restoring diabetes-induced genital pathology.
Animals ; Arousal ; Atrophy ; Clitoris ; Diabetes Complications ; Diabetes Mellitus ; Dyspareunia ; Estradiol ; Estrogens ; Female ; Genitalia ; Hemodynamics ; Humans ; Hyperglycemia ; Lubrication ; Models, Animal ; Plasma ; Progesterone ; Receptors, Androgen ; Receptors, Steroid ; Testosterone ; Vagina