The Penis as a Barometer of Endothelial Health

Andrew R McCullough, MD, FACS Department of Urology, New York University School of Medicine, New York,
NY Rev Urol. 2003; 5(Suppl 7): S3S8.
Copyright 2003 MedReviews, LLC

Original article

One of the aspects of erectile dysfunction which has been clarified by the introduction of phosphodiesterase-5 inhibitor therapy is the close relationship between the health of the cardiovascular endothelium and erectile dysfunction. Clearly, therefore, erectile dysfunction needs to be seen as not only a sexual issue but possibly as an indicator of a life-threatening disease.

Other pages on this website about erectile dysfunction, erectile dysfunction and impotence

Home ] Treatment of psychological (psychogenic) ED ] Treating ED caused by anxiety ] Self hypnosis for erection problems ] Hypnosis ] [ ED & cardiovascular disease ] Viagra and Effective treatment of ED ] Background Information About Treatment ] The Science of Treating Erectile Dysfunction ] Viagra and Similar products ] Intercavernosal Treatmend - Drugs and Implants ] Erectile Dysfunction - Home Treatment Strategies ]



Masters and Johnson were the first researchers who introduced the idea that ED was mostly psychological in origin and could be cured with psychological therapy and behavior modification.

 It was only from the 1970s onwards that the association between ED and diabetes, spinal cord injury, pelvic surgery, traumatic injury and so on was recognized.

A whole series of tests including psychiatric examination, hormonal profiles, ultrasonography, penile angiography, and cavernosometry were developed in response to the concerns that arose when the field of penile implant surgery developed.

Unfortunately these tests did not clarify the origin of ED, but they did make it very clear that there was a strong association between ED and cardiovascular disease.

There is an increasingly clear link being demonstrated between erectile dysfunction and the risk factors for atherosclerotic disease.

For example, one recent study of men with erectile dysfunction revealed that just under half had hypertension, round about a fifth had diabetes mellitus, almost a fifth were smokers, and almost four fifths had a body mass index greater than 26 kg/m2, while almost exactly two thirds had low-density lipoprotein cholesterol at a level greater than 120 mg/dL.

Further epidemiological findings which have demonstrated a clear link between ED and cardiovascular risk have been obtained from the Massachusetts Male Aging Study.

The new therapies for erectile dysfunction of intracavernosal injection and intraurethral application of MUSE pellets might have been interpreted
as lessening the need for understanding of the underlying etiology of ED.

This goal directed approach was practical in terms of generating erections for the men concerned, however it certainly did not deal with the interpersonal aspects of the relationship which may have been contributing to the man's sexual dysfunction, and more particularly it did not address any underlying issues of cardiovascular disease.

It's a fact that at the moment most prescriptions for phosphodiesterase-5 (PDE-5) inhibitors are written by general practitioners rather than urologists.

This may be one of the reasons why erectile dysfunction continues to be perceived as nothing more than a quality-of-life issue, although attention is now being more focused on the significance of the dysfunction in terms of overall men's health (at this point it's worth remarking that apparently fewer than one man in four with ED seeks help for it -- such is the apparent embarrassment or social stigma associated with the condition).

As we have already seen from the pages of this website, the penis is a very complicated and hydraulic system which response to both sympathetic and parasympathetic nervous system, with the mechanism of erection that involves both arterial pressure and veno-occlusion.

You may also recall that the process of erection is dependent on the presence of both neuronal and endothelial nitric oxide, which is present because of the activity of an enzyme known as nitric oxide synthase (NOS).

Any disease process which reduces the level of NOS obviously will reduce the potential for erection, and make a man more subject to the vagaries of erectile failure.

The significant point here is that reduction in the level of NOS in the endothelial tissue is associated with cardiovascular disease and endothelial dysfunction. And damage to the endothelium is often seen well in advance of the development of clinically apparent to vascular disease.

At this point it's well worth emphasizing that in men under 35 most ED is undoubtedly psychological in origin: it's usually a manifestation of performance anxiety.

And in fact it's also worth keeping in mind that because of the close association between performance anxiety and erectile dysfunction, even men who have a clearly organic basis for their dysfunction will undoubtedly have a level of performance anxiety that undermines the foundation of whatever erectile function they have left.

That is why a treatment approach that focuses on the physical aspect of arousal and reduces the anxiety level of the man concerned can have a major impact on his erectile capacity even when he is dysfunction has an organic cause.

Anyway, the point is this: since there is such a close association between endothelial dysfunction and erectile dysfunction, could ED be used as an indicator of heart problems and circulatory system disorder?

The answer to this is a very clear "yes". ED manifests itself much earlier than critical arterial stenosis of the coronary arteries, or indeed before diabetic peripheral neuropathy or hypertensive cardiomyopathy. In short, ED is an early warning sign, which may indicate that a man's cardiovascular system is in desperate need of attention and that an aggressive approach to the control of, for example, dyslipidaemia may be required.

Furthermore, enquiring about the level of a man's erectile dysfunction provides an easy opportunity to work out how serious his endothelial disease might actually be.

One complicating factor in this whole syndrome is that many of the drugs used for antihypertensive therapy can in fact induce erectile dysfunction. It appears that up to 45% of men with hypertension who also have ED blame the drug regime for hypertension as the cause of their ED.

If a man has a regular sex life and he has come to the conclusion that his ED is the product of drugs which is taking, he is likely to stop taking the drugs whenever he wishes to have sex.

Whatever the reasoning, the outcome is the same: that his compliance with the drug regime is poor. It's certainly true that many drugs do in fact have an association with erectile dysfunction, although often the effect can be reduced by using different drugs, or by amending the drug regime.

Once again, the active involvement of the man's doctor is essential to ensure that both the underlying condition of which he is receiving treatment is satisfactorily addressed, and his erectile dysfunction is minimized.

Doctors should constantly monitor the conditions for which they are responsible in their patients: this may be hypertension or dyslipidemia, both of which are associated with cardiovascular disease. Obviously in the case of diabetes, a tight glycaemic control regime will lead to fewer retinal and neurological symptoms.

One of the most powerful tools in understanding how patients are responding to treatment, or how their symptoms are developing, is the patient history.

So, for example, when talking to a diabetic patient, a doctor may well enquire about chest pain, urinary frequency or claudication, but they should also enquire about one of the most obvious symptoms of endothelial disease, which is the presence of erection problems. In one study, only 14% of diabetic patients were actually asked about their sexual history.

Obviously a man always knows his sexual health, even if he takes steps to disguise it from others. But in an interview with the doctor, a question about a man's sexual capacity provides an opportunity for both the patient and the doctor to discuss the relationship between ED and cardiovascular disease.

This can remove shame and ensure that the man understands the connection between his physiology and the appearance of symptoms of ED.

Although we have gained the impression that Viagra and its counterparts are effective medication, therapeutic efficiency of these drugs is actually around 75 to 80%.

This means that a significant number of men have erection problems due to relationship issues that are not dealt with by establishing sexual capacity through drug therapy.

In other cases, the man's endothelium may be so damaged that PDE-5 inhibitors simply do not have any effect, which again can be useful indicator: if there are no relationship issues and Viagra does not produce an improvement in erectile capacity, then clearly it is a matter of urgency that man should be investigated for serious vascular disease.

And despite the fact that only 25% of men seek treatment for their erectile dysfunction, we should remember that it was not so long ago that fewer than 6% of men were receiving treatment for ED. So great strides have been made in the treatment of ED, but its stigma is still strong.

There's a lot of shame around the issue, and doctors and patients alike frequently avoid discussing it. It's important that a man's general practitioner is fully educated in the management of ED and that patients are questioned about their ED to ensure that it is not a manifestation of some much more serious underlying issue.


The Penis As A Measure Of Endothelial Health

Andrew R McCullough, MD, FACS Department of Urology, New York University School of Medicine, New York, NY Rev Urol. 2003; 5 (Suppl 7): S3S8.

This is an interpretation of the main points of that article.

The causes of erectile dysfunction (ED) are often thought of as mostly organic. Phosphodiesterase-5 inhibitors such as Viagra have been of great importance in the treatment of ED and have promoted research and understanding of the etiology of ED - and this research has shown the close association of erectile problems with cardiovascular disease.

Endothelial dysfunction is often revealed initially by problems with erection, and should there for be a warning sign for investigation into cardiovascular risk. ED is much more than a quality-of-life issue.

Home ] Treatment of psychological (psychogenic) ED ] Treating ED caused by anxiety ] Self hypnosis for erection problems ] Hypnosis ] [ ED & cardiovascular disease ] Viagra and Effective treatment of ED ] Background Information About Treatment ] The Science of Treating Erectile Dysfunction ] Viagra and Similar products ] Intercavernosal Treatmend - Drugs and Implants ] Erectile Dysfunction - Home Treatment Strategies ]

During the past three decades the connection between erectile dysfunction and organic disease has become clear. Before this, aside from advanced diabetes, pelvic trauma, the after-effects of pelvic radiation, surgery and spinal cord injury, the cause of ED was not always apparent.

But it has gradually become clear that ED is strongly associated with cardiovascular disease processes. Anecdotal, experimental, and scientific evidence now shows a clear link between erectile dysfunction and the risk factors for atherosclerotic cardiovascular disease.

In one study of 154 men with ED, 44% displayed hypertension, 23% showed diabetes mellitus, 16% were tobacco users, almost 80% had a body mass index greater than 26 kg/m2, and 74% had unhealthy levels of LDP cholesterol level (in excess of 120 mg/dL.2)

Also, the 10-year study of the MMAS has demonstrated that the original findings linking ED with cardiovascular risk factors were correct.

The development of i ntracavernosal and intraurethral prostaglandin and Viagra therapies may have led to the belief in the medical community that there was no real need to understand the etiology of ED. If the recommended therapy worked, why understand the etiology? Many urologists were goal-directed and de-emphasized the importance of diagnosis: the man was given information on the therapeutic options and left to make a decision.

But, by the end of 1998, three fourths of new Viagra prescriptions were being written by ordinary physicians: this required a  "Process of Care" model to guide non-specialist physicians in the treatment of Erectile Dysfunction.

This was written by experts in the area of male sexual dysfunction, so that non-urologists were correctly guided through the clinical approach to ED. In many ways, ED is still seen as a quality-of-life issue. And that is understandable. The problem is that research shows few men are willing to bring the subject up unless their doctor raises the issue first. Even though there is much more knowledge about erectile problems, may men and partners are still embarrassed by the subject. The result? A horrendous statistic: fewer than 25% of men with ED seeking medical care for this problem.

Yet when we ask what the significance of ED might be as a possible diagnostic clue for peripheral vascular disease, the whole issue begins to look much more serious.

The Penis And The Endothelial System

The penis is responsive to both sympathetic and parasympathetic nerve system stimulation, and it also responds to active vascular flow and passive venous occlusion. There is a significant endothelial surface which is interlaced with smooth muscle fibers.

An erection involves lowering of the sympathetic smooth muscle contraction, and an increase in the  parasympathetic smooth muscle relaxation.

There is an associated flow of blood into the penis which causes the endothelial spaces to fill, with a concomitant compression of the small veins which emerge from the tunica albuginea.

The whole process is regulated by the level of nitric oxide, produced in response to the activity of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively). The penis contains a high level of Nitric Oxide, so any disease which reduces the level of NO or the enzymes responsible for its synthesis will have a negative impact on erectile function.

E ndothelial NOS levels are usually reduced when there is manifest cardiovascular disease and endothelial dysfunction. The scientific evidence which links NOS deficiency and ED is very compelling. But despite the strong link between ED and endothelial dysfunction, ED is not necessarily related to decreased NOS levels.

For example, a young man who suffers from sexual performance anxiety and loses his erection on the occasion of his first sexual experience is in difficulties because his sympathetic nervous system is overactive, which means the smooth muscles in his penis cannot relax; therefore, his penis never gets erect - or if it does, it loses the erection quickly.

Indeed, in men aged 35 or younger, men with no significant endothelial disease or neurologic risk factors, provided they are not using drugs or medications known to interfere with erectile function, most erectile problems are psychological. The finger of blame for erectile issues points firmly at performance anxiety in men of this age group.

But for older men, where there is a strong relationship between ED and endothelial dysfunction, the question needs to be asked if penile dysfunction is an indicator of endothelial dysfunction.

Why Diagnose ED?

Assessing The Degree Of Underlying Disease

We know Erectile Dysfunction can be a sign of a more serious underlying disease. A man with ED is likely to be hypertensive, hyperlipidemic, obese, diabetic, or aging. However, the key thing here is that erectile issues are an early sign of diseases, and it is obvious long before coronary arterial stenosis, retinopathy, hypertensive cardiomyopathy, or diabetic peripheral neuropathy.

For example, the presence of ED in a man of 52 is a sign that his endothelium is in bad health, and that drug therapy rather than diet or lifestyle changes may be needed. Therefore, enquiring about ED is a comparatively simple way to establish the severity of a man's endothelial disease.

ED As A Side-effect Of Drugs

Many of the medical conditions from which we suffer remain out of our awareness, so for example you might not be aware of your diastolic pressure or cholesterol level: but what you will know about is the side-effect of any treatment for these conditions.

So, for example, almost half of men with hypertension have ED which they ascribe to the drugs they take for Erectile Dysfunction. And, when a man knows he is going to have sex on a regular basis, he may stop taking his mediation to accommodate his sexual schedule. This will, of course, affect the effectiveness of treatment of his hypertension.

The reason why medication can cause erectile problems remains unclear. It's probably a combination of factors such a lowered blood pressure, organic effects of the medication, and the side-effects of the disease itself. 

But, whatever the cause, the outcome is limited compliance with drug therapy. One way to avoid this is to ensure the doctor takes account of the side-effects and discusses the treatment options with the patient thoroughly. There is no necessity - in most cases - for drug treatment to cause ED.

Further more, use of the Sexual Health Inventory for Men before treatment for high blood pressure will help to identify men with latent ED, and their medication may be adapted accordingly.

Most conditions have a defined progression, and must be treated: so, for example, control of hypertension and dyslipidemia are definitely linked with the prevention of cardiovascular disease. For the doctor, physical examination and patient history may reveal very obvious symptoms of disease: for example, ED is a powerful indicator of endothelial disease.

A man may avoid sexual intimacy with his partner, but he knows that his penis is not working correctly. When his doctor asks him about heart disease, it is possible and probably necessary to explain how the two conditions may be linked to questions about angina and claudication. The doctor needs to take the chance to educate the patient about the connection between erectile dysfunction and cardiovascular disease. It is also a useful strategy for demystifying and reassuring the patient about the origin of his disease.

When Viagra Does Not Work

But making the d iagnosis and recommending Viagra is not enough. In many cases, Viagra does not work. About 25% of cases, in fact. Having said that, it does improve quality of life for the men for whom it does work.

Nonetheless, treatment failures with this class of medication needs to be regarded with more gravity than they have previously been - some of the failures are attributable to relationship issues which need to be resolved or cannot be resolved; others are attributable to endothelial disease which is so advanced that the success rate of PDE-5 inhibitors is drastically reduced.

The more serious the underlying endothelial disease, the less the bodily response to Viagra and other PDE-5 inhibitors. In short: if drug therapy (Viagra or its counterparts) fails when a man is complying with all the instructions, there is either a powerful psychological component to his problem or he has severe peripheral vascular disease.

How To Tell The Difference?

A man with psychogenic ED and a man with severe vasculopathy have different histories: and the man with vasculopathy may be a "walking time bomb." In other words, it's wise to regard PDE-5 inhibitor failures as the consequence of severe peripheral vascular disease until evidence merges to the contrary. Endothelial disease is often a forerunner of clinically manifest vascular disease. "The penis is an endothelial organ. Its failure to respond to PDE-5 inhibitors should be treated as a serious symptom."


The treatment of ED is more advanced now than ever before: only a decade or two ago, less than than 6% of men with erectile dysfunction were receiving treatment. Now, the figure is up to one man in four, and most of these men receives care from general practitioners.

For the author of this website, the main factor here is that the stigma of erectile dysfunction is still so great that both doctors and patients often avoid the topic. Time and embarrassment are the key reasons for this.

But because ED is sometimes an early sign of endothelial disease, and because men prescribed medication for other conditions may not take the medication if it induces ED, care and scrutiny by the doctor is needed. The functioning of a man's penis can truly be a measure of the health of his endothelial system.

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