December 1, 2005

Male Erectile Dysfunction: How Exactly Does Viagra Work?

By Dr. Howard Glicksman

After his usual appointment, in which we had touched on every aspect of his health, Mr. C. was just about to leave my office, when he turned and, feigning forgetfulness, quietly whispered to me if I could give him a prescription for Viagra.  I ushered him quickly back into the examining room so we could discuss his request.  I made sure his symptoms met the criteria for erectile dysfunction (not just what he thought met the criteria), there were no medical contraindications, and then I explained how it worked and how to use it.  After this I gave him a sample of the drug that contained literature inside to read.

The following week Mrs. C. happened to be in my office for her usual follow-up visit.  As I entered the examining room a bright smile came over her face and she laughingly motioned me to sit down quickly so she could tell me her story.  She said that for years she and Mr.C. would spend their late evening hours propped up in bed, each reading a book or magazine, prior to drifting off to sleep. 

Last week while they were in their respective  positions, Mr.C. suddenly became very angry and upset and exclaimed “I knew it wouldn’t work!”  Mrs. C. was bewildered by the outburst and inquired of Mr. C. what exactly he was talking about.  He went on to tell her that he had asked me for some Viagra earlier that day and he had indeed taken some that evening  But nothing had happened.  He had not attained the erection he hoped for. 

Needless to say, Mr.C. had forgotten everything that I had told him and evidently had not read the instructions, or if he had, had not understood them.  Before the advent of Viagra, the treatment of erectile dysfunction had largely consisted of either using strong elastic bands at the base of the penis with a vacuum device, or injecting medication directly into the penis.  Either way, when one used one of these “therapies” one immediately knew if it had worked or not.              

The difference being that with Viagra, it simply enhances the natural biomolecular and physiological processes that are involved in erectile function.  One need only take the drug within a few hours of intended sexual activity, and if it is effective, the available biochemical reaction needed to enhance erection still available in the body will allow foreplay to do the rest.

Mr.C. had incorrectly assumed that without any physical or emotional interaction with his wife, an erection would occur spontaneously after he had taken the Viagra.  He had been very disappointed.  But Mrs. C. gleefully concluded her story by telling me that as she leaned over to console him in his misfortune, she inadvertently brushed her hand against his inner thigh resulting in Mr.C. quickly experiencing a very firm erection. 

With that we both burst out laughing, considering the comedy of errors that had gone from initial disappointment, to compassionate support, and ending with surprised enjoyment.  Viagra can do that for some couples.  But how does it work?  Let’s look at the anatomy and physiology of penile erection and the biomolecular processes behind it.       

Gross Anatomy and Histology

I think most people would agree that in order for the homonid species to have come into existence the male external genitalia with its associated functions was absolutely necessary.  The male penis serves two purposes: the release of urine and its chemical contents derived from the kidney, and the release of sperm and seminal fluid during ejaculation for reproduction.  The latter function is what concerns us in this column.

The condition now known as erectile dysfunction, but up until recently more commonly as impotence, points to a serious matter that requires a neo-Darwinian explanation.  For not only does impotence refer to the inability to have an adequate erection to engage in sexual intercourse, but the word itself strikes at the heart of all that is sacred and holy in the life of an evolutionary biologist.  To be impotent is to be; ineffective, powerless, or helpless, all the characteristics of a life form that is surely destined to fail in the battle for the survival of the fittest.  Being impotent is mutually exclusive to the concept of fitness and therefore its opposite, the development of potency, which is a necessary function for neo-Darwinism, needs to be explained in logical and scientifically verifiable terms.

Penile erection is achieved by hydraulic pressure.  Running the length of the penis, surrounding the urethra and above and to each side of it, are the corpus spongiosa and the corpus cavernosa.  These are tube shaped venous chambers that are surrounded by strong fibrous tissue.  They have the capacity to be filled with blood, upon proper neural stimulation, by dilation of the arteries supplying blood to this region, which combined with partial occlusion of venous outflow, results in erection.  (see Figures 1 & 2)

Figure 1

Figure 2

How the structures contained within the penis just happen to consist of  tissue with the underlying properties, and be positioned in the right place, for proper reproductive function, would seem to require explanation.       

Neurovascular Physiology

The “proper neural stimulation” for penile erection is mediated through the autonomic nervous system which is divided mainly into the parasympathetic and sympathetic divisions.  This largely involuntary part of neuromuscular control sends messages from the central nervous system to various organ systems to maintain proper function and homeostasis.  Some of its effects include: control of heart rate and degree of contraction (sympathetic increases, parasympathetic decreases) , motility of, and secretion in, the digestive  tract  (parasympathetic increases,  sympathetic decreases),  and,  for  our purposes here, vasodilatation  (parasympathetic for external genitalia,  sympathetic  for skeletal muscles) and vasoconstriction (sympathetic in most organs). See:

Messages from either the higher centers in the brain (psychogenic stimulation), or sensory fibers from the penis, particularly the glans, (reflexive stimulation) result in messages from the pelvic parasympathetic nerves being sent to the vessels in the penis.  This causes vasodilation and the filling of the corpus spongiosa and cavernosa resulting in erection.  As sexual intercourse takes place, continued psychogenic, and particularly, reflexive sensory messages, causes this parasympathetic stimulation to continue until orgasm.

The emission and ejaculation of semen is a function of the sympathetic nervous system that involves smooth and skeletal muscle contraction of the organs and muscles in the male genital tract.  With this sympathetic response resulting in completion of the sexual act, parasympathetic stimulation of penile vasodilation and erection is reversed and demutescence  takes place.

One can immediately see that this is a well controlled system that requires voluntary human interaction and intact involuntary human neuromuscular physiology in order for it to achieve its set goal, ie propagation of the species.  Any interruption or delay in nerve impulse transmission, or defect in local penile blood flow, is likely to cause the human male to suffer from erectile dysfunction.  Common medical conditions that result in this circumstance are: diabetes, (which affects the nerves and arteries), arteriosclerosis (hardening of the arteries), chronic neurological conditions (such as multiple sclerosis), chronic alcoholism (affects nervous system) and a history of pelvic surgery or trauma etc.

Each of the parts mentioned are absolutely necessary for proper erection and ejaculation.

One needs the properly outfitted penis, the internal genital organs for sperm and seminal fluid production and transmission, and the neuromuscular set-up for controlling the action of sexual reproduction.  But we as yet have not addressed what is going on at the biomolecular level and it is to this now that we turn.  For without a  full understanding of what is going on biochemically, one cannot appreciate the genius, worthy of the Nobel prize, behind the creation of Viagra.  Evolutionary biologists are likely to be among some of the people who have benefited from this discovery, yet it seems to me that they have never bothered to ask themselves how the human male developed the capacity for proper erectile function (sans Viagra) in the first place.      

Biomolecular neuroelectrophysiology

Some of you may want to review my prior columns called Wired For Much More than Sound Parts I, II & III, which reviews nerve and muscle cell function in depth.  Below I have provided a brief summary in order to help you appreciate and understand what is ultimately needed for adequate erectile function to take place.


We have now reached the point where all of the action takes place. It’s a sort of alphabet soup of biomolecules that are formed to result in vasodilation and ultimately penile erection. Here’s how it works.

The released neurotransmitters (NANC) from the parasympathetic nerves stimulate the enzymatic formation of nitric oxide (NO) within the endothelial cells that line the penile blood vessels.  This gas diffuses from these cells into the smooth muscle cells that surround them.  Once inside the smooth muscle cells the NO binds to and activates an enzyme called guanylate cyclase which converts GTP (guanosine tri-phosphate) into cGMP (cyclic guanosine mono-phosphate) which in turn activates other enzymes causing relaxation of the muscle fibers and vasodilation.  The resulting vasodilation of these blood vessels causes a quick increase of blood flow into the corpus spongiosa and cavernosa effecting an erection that makes human reproduction possible.  (see Figure 3)

Figure 3

But we’re not quite finished yet.  As fig.3 clearly shows, there’s the matter of this enzyme called PDE 5 to consider.  Phosphodiesterase 5, is the specific enzyme that rapidly breaks down  cGMP  in the penile blood vessels, resulting in the potential reversal of the vasodilation needed for erection.  So in order to maintain an erection requires continual parasympathetic output, largely by tactile reflexive stimulation (ie local sensory stimuation of the penis), which results in a continuous flood of NO and cGMP to combat the effects of PDE 5 until ejaculation can take place.

One can immediately see the utility for the function of PDE 5 since without it, once an erection occurs it could take a very long time for it to deflate unless ejaculation comes about.  Contrary to what you may think, having a prolonged and very hard erection can be painful and cause serious damage. 

But what about the opposite consideration?  What if the concentration and associated enzymatic activity of PDE 5 were so powerful as to not allow cGMP to exist long enough to effect adequate vasodilation even with continuous parasympathetic stimulation?  With this scenario penile erection would be impossible, sexual intercourse, as we know it, would never have taken place, and we would not exist.           

Viagra to the Rescue

So where does Viagra fit in?  The cause of most men’s erectile dysfunction seems to relate to the penile blood vessels’ lack of sensitivity to the vasodilatory effects of cGMP.

In other words, for whatever reason, there seems to be a resistance present within the mechanism of penile blood vessel dilation that causes it not to respond as readily as it once did, in bygone days, to the same amount of psychogenic and reflexive stimulation.

A quick review of the neurobiomolecular physiology behind erection will show that there are several places within the system that controlled intervention could possibly help relieve the condition of erectile dysfunction. 

  1. Increase NO produced in the penis in response to parasympathetic stimulation
  2. Increase NO induced enzymatic production of cGMP within the penis
  3. Limit activity of PDE 5 to allow cGMP to have a more prolonged effect in the penis

Viagra, also known as sildenafil, is a selective phosphodiesterase type 5  (PDE 5) inhibitor which potentiates the relaxation of smooth muscle in the corpus spongiosa and cavernosa of the penis, resulting in erection.  So one can see that option #3 is where Viagra fits in here.

What about Macroevolution?

As my previous columns have similarly highlighted, the hydraulic system for adequate penile erection to allow for human sexual reproduction and survival of the species is irreducibly complex at both the gross anatomy and neurophysiological levels.  All of the components mentioned above require a detailed explanation of not only their genetic coding and  biomolecular construction, but also their having come together as a functioning system. 

But the task presented here; of explaining how and why Viagra works for erectile dysfunction, should make one pause and consider another level of complexity that goes far beyond mere components coming together to perform a function.  Notwithstanding the science fiction of “indirect Darwinian pathways” to explain the latter, what I’m referring to here is the complexity of survival capacity which I spoke about in my column on hemoglobin last year. 

When considering what we know to be necessary for adequate erectile function, it is evident that only trying to explain where the individual parts came from and how they came together to function is woefully insufficient to explain this vital function for human survival.  One must also consider such things as:

  1. What concentration of neurotransmitter is present for a given amount of stimulation?
  2. What degree of neurotransmitter activity is necessary for adequate NO production?
  3. What degree of NO concentration is necessary for adequate cGMP production?
  4. What degree of cGMP concentration is needed for adequate vasodilation?
  5. What amount of PDE 5 activity allows for adequate but not prolonged erection?

For the mere existence of parts should not assume a system of function, and the mere existence of a functioning system should not assume adequate capacity for survival. 

Next time female sexual function and some of the consequences of oral contraception will be highlighted.  See you then and have a Merry Christmas and a Happy New Year

Dr. G.

Howard Glicksman M.D. graduated from the University of Toronto in 1978.  He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida.  He now practices palliative medicine for a Hospice organization in his community.  He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being. 

Copyright 2005 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 12.01.05