Erectile Dysfunction as a Cardiovascular Impairment

Robert Fried

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124200418
• Topic: Biological Sciences
• Subtopic: Human Anatomy & Physiology
• Index: Biological Sciences

Erectile Dysfunction as a Cardiovascular Impairment organizes and summarizes the many aspects of biology and metabolism in cardiovascular and sexual function. Coverage includes how blood vessels are discovered to work, their role in hypertension, atherosclerosis, type-2 diabetes, oxidative stress, metabolic syndrome, and erectile dysfunction.

• Unifies medical disorders linked to cardiovascular and heart disease as endothelium impairment, to whichvasculogenic erectile dysfunction is now added and given equal rank for the first time
• Presents hypertension, atherosclerosis, metabolic syndrome, and erectile dysfunction as symptoms of disease
• Offers clinical research on vasculogenic erectile dysfunction predicting onset and severity of heart disease

Chapter 1

Introduction

This chapter defines erectile dysfunction (ED) by the criteria in the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV-TR, 2000), and proposes the future inclusion of a medical cause diagnostic category corresponding to systemic as well as penile vascular impairment, purportedly the most common presentation of ED. The chapter further distinguishes between sexual dysfunction and low or absent sexual desire relating vasculogenic ED also to common cardiovascular (CV) health hazards that rarely affect desire. The chapter details the nature and the role of the vascular endothelium and the role of nitric oxide (NO) in the sequence of events in sexual arousal leading to penile erection—the ACh/NO/cGMP pathway. It ends by detailing the progressive age-related impairment in endothelium function and loss of sufficient formation of NO for attaining and sustaining penile erection.

Keywords

Acetycholine (ACh); Aging; Atherosclerosis; Cyclic Guanosine Monophosphate (cGMP); Erectile Dysfunction (ED); Endothelium; Heart Disease; Hypertension; L-Arginine; Nitric Oxide (NO); Penis; Phosphodiesterase Type-5 (PDE5); Sexual Arousal; Sexual Performance; Vasa Vasorum; Vasculogenic Erectile Dysfunction; Vasodilation; VIAGRA®

“If we do not change our direction, we are likely to end up where we are headed.”

—Ancient Chinese proverb

1.1 Erectile Dysfunction—as Presently Defined

The common term “erectile dysfunction” (ED) is “Male Erectile Disorder” in the current Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association. It is said to be a persistent or recurrent inability to attain or to maintain an adequate erection to completion of the sexual activity. It is a disturbance causing marked distress or interpersonal difficulty, an ED not better accounted for by any other diagnostic categories except mental retardation and personality disorder, and one that is not due exclusively to the direct physiological effects of a substance, e.g. a drug abused, a medication, or a general medical condition (APA—DSM-IV-TR, 2000).¹ The definition assigns etiology to other than medical causes thus seemingly excluding vascular/vasculogenic ED, now considered to be the most common form found among American men.

By no means is each and every case of chronic ED vasculogenic, but the overwhelming majority of cases that appear to develop in adults—estimated at about 90 percent in American men—and to follow an age-related timeline, fit that definition. There are, of course, other causes of ED, some due to hormonal imbalance, and others with an emotional basis, but they are not the concern of this monograph.

The recommendation to include diagnostic criteria for a medical basis of ED in subsequent editions of the DSM is made in the Journal of Sexual Medicine,² and it is consistent with the theme of this monograph. In fact it is essential to make both the medical and the mental health services community aware of that medical basis so as to improve health care delivery beyond simply treatment of ED per se.

1.2 The Aim and Scope of this Monograph

This monograph will make the general case and document the research and clinical evidence that ED is indeed caused by a medical condition: impaired vascular endothelium resulting in reduced bioavailability of nitric oxide (NO). NO is a biologically active gas, the link between sexual arousal and erection. It is derived in the body principally from the amino acid L-arginine and from dietary nitrates. NO mediates between the arousal-triggered release of acetylcholine (ACh), and the formation of the vasodilator, cyclic guanosine monophosphate (cGMP), in the ACh/NO/cGMP pathway to penis cavernosal relaxation, engorgement, and erection.

The advent of phosphodiesterase type-5 (PDE5) inhibitors including VIAGRA®, Cialis®, and Levitra®, have made the medical and psychiatric/psychological community aware that there are medical treatments for the most common form of ED, but it is not clear to most practicing clinicians how and why they work except in the most vague terms that they somehow influence blood flow and thus erection. Not being familiar with the ACh/NO/cGMP pathway, many suspect that these meds might just treat the psychological basis for ED.

There are precedents in medicine to parallel the disjunction between emotional disorder and medication treatment. For instance, bipolar disorder is a mood disorder that is treatable with medications. Thus, there is an understanding that medications can affect mood without most practitioners understanding the brain physiology basis for the mood, or the disorder, except in vague terms such as “neurotransmitter biosynthesis” that only specialists really know. Thus, it is not unreasonable to figure that meds can treat ED even if one holds that ED is basically an emotional disorder.

The reason for this information gap is that the clinical and basic research leading to our understanding of the ACh/NO/cGMP pathway to cavernosal relaxation and penis engorgement and erection, and related physiology, is found in thousands of scientific reports in hundreds of different journals straddling many dozens of different subspecialties, published over the past three decades. It would be an impossible task for any practicing clinician to keep up with this avalanche of data.

For example, there is an estimated 850,000 licensed physicians in the US. Less than half that number (about 300,000) subscribe to the Journal of the American Medical Association (JAMA). The New England Journal of Medicine (NEJM) has about 200,000 subscribers, and Annals of Internal Medicine has about 110,250 subscribers. These are major journals. Even so, basic research and clinical trials relevant to the present concerns appear in specialty journals such as Archives of Biochemistry and Biophysics, Ultrasound Medicine and Biology, and Vascular Physiology, where researchers basically talk to each other; and also in better known journals with a narrow-focus regular readership such as Diabetes Care, Hypertension, and the Journal of the American college of Cardiology, to name just a few. The information often doesn’t filter down to the rank and file practitioners who really most need it to serve patients well.

This monograph synthesizes information from a wide range of subspecialties, and in most cases indicates the source by naming the journal where cited reports were published. Naming the source is especially important here because it establishes the credibility of information drawn from a wide range of research subspecialties, each providing what amounts to a handful of tiles to form the overall mosaic: ED as a cardiovascular impairment. Furthermore, naming the journal sources also gives the reader insight into the complexity of contemporary research: The simple days are pretty much a thing of the past when, for instance, penicillin was discovered when an in vitro bacterial culture was inadvertently destroyed by a contaminating spore (penicillium) in Dr. Alexander Fleming’s lab, or the treatment of diabetes when Dr. Frederick Banting injected pancreatic extract into a patient, or when Dr. Barry Marshall established the cause of most ulcers by downing an “infectious broth” holding Helicobacter pylori.

1.3 The Prevalence of Erectile Dysfunction

According to a 2007 report from the Johns Hopkins Bloomberg School of Public Health, more than 18 million American men 20 years old, or older, experience some degree of ED, from mild-episodic to severe-sustained ED.³ The report pointed to causes ranging from cardiovascular and heart disease to diabetes. Advances in medical science are now shifting the attention of many clinicians from treating the mind to treating the body.

There is now overwhelming evidence that most men with ED can attribute this calamity to cardiovascular and metabolic disorders including hypertension, atherosclerosis, CHD, type-2 diabetes, and metabolic syndrome. It is also now known that the progress of this assortment of medical disorders is further enhanced by oxidative stress, by the progressive age-related decline of androgenic hormones, and by changes in energy storage and marshaling control-hormones.

For better or for worse, the timeline of these progressive age-related calamities for each one of us is pretty strictly subject to the dictates of genetics. It is pretty well established, and scientific proof abounds to show that we have little power to retard it. However, with the help of poor nutrition and an unhealthy life style we can readily accelerate it.

We are frequently cautioned by health authorities via media and other sources that unhealthy nutrition and sedentary lifestyle are at the very core of the cardiovascular afflictions that thwart vigorous and enduring erectile function. These reports bolster the idea that when it comes to lovemaking, our diet can either make us or unmake us because our diet is principally responsible for these medical disorders that result in ED. In fact, our diet by itself is not at fault. The most recent scientific findings teach us that:

• High blood pressure, atherosclerosis, insulin resistance, visceral adiposity (metabolic syndrome), and ED are natural, progressive, age-related cardiovascular conditions with a timeline determined principally by our genes.

• The progress timeline of these conditions can be accelerated by a diet that is poor in certain nutrients and micronutrients, and either too poor or, paradoxically, too rich in antioxidants.

• High blood pressure, atherosclerosis, and insulin resistance, leading to cardiovascular and heart diseases, diabetes, metabolic syndrome, and the ensuing ED, may not be “diseases” as we understand that term, but the “presenting clinical symptoms” of an underlying natural process of systematic degradation and ultimate dysfunction of the endothelium, the cell-layer lining the blood vessels throughout the body.

• Endothelium dysfunction adversely impacting the ACh/NO/cGMP pathway is causally linked to high blood pressure, atherosclerosis, insulin resistance, oxidative stress, metabolic syndrome, declining testosterone, changes in sensitivity/resistance of appetitive control hormones, and ultimately, ED, by interference with the formation of endothelium-derived NO.

• The endothelium serves a vital physiological control function that is undermined in part by oxidative stress and is in part linked to a diet that fails to supply certain essential nutrients and micronutrients that support the proper balance of endogenous and exogenous antioxidants.

• Endothelium impairment is now recognized as the primary cause of most cases of ED, and in fact, prescription medications such as VIAGRA are used to bolster its flagging function.

• While even the “healthiest” diet and lifestyle may not stop progressive aging, they can significantly keep it to its natural individual dictates, whereas poor diet and sedentary lifestyle can speed up endothelial aging as noted by rapidly progressing hypertension, atherosclerosis, and insulin resistance.

These findings may seem outside the mainstream of current intuition regarding what leads to what, that leads to ED. Nevertheless, while perhaps not widely known yet, these assertions constitute the consensus of contemporary scientists spanning those subspecialties examining the clinical and the laboratory links between cardiovascular risk factors and ED.

The epidemiological derivative of the links of cardiovascular disorders and ED to endothelium impairment gives rise to a formulation of their interrelationship that strongly suggests that they are all, in fact, symptoms of underlying blood vessel disease. Many investigators worldwide now hold that view. Thus, this book proposes no unconventional theory of the cause of ED, and no unconventional theory of its treatment outside the mainstream of up-to-date medical research. The ideas and assertions are those of the rank and file in medical laboratory and clinical research whose journal publications are abstracted, paraphrased, and cited here. Their individual research forms fractions of a whole, and the synthesis of these disparate findings into that coherent “whole” is, howev...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Reviews
• Preface
• Acknowledgments
• Chapter 1. Introduction
• Chapter 2. Measuring and Evaluating Function, Impairment, and Change with Intervention
• Chapter 3. Cardiovascular Health Hazards Impairing Sexual Vitality
• Chapter 4. Oxidative Stress Damages the Endothelium
• Chapter 5. Metabolic Syndrome Impairs Erectile Function
• Chapter 6. Asymmetric Dimethylarginine Impairs Nitric Oxide Bioavailability and Jeopardizes Cardio-Sexual Function
• Chapter 7. Arginine Supplementation in Cardiovascular Disorders
• Chapter 8. Arginine and Arginine-Combinations in Treatment of Erectile Dysfunction
• Chapter 9. The Polyphenolic Antioxidant Resveratrol, the Carotinoid Lycopene, and the Proanthocyanidin Pycnogenol
• Chapter 10. Selected Micronutrients and the Metabolic Basis for Their Support of Endothelial Health and Erectile Function
• Index