Erectile Dysfunction White Paper

Introduction & Prevalence

Erectile dysfunction (ED) is an inability to get an erection or maintain a harder erection required for penetration. It is one of the most common sexual health concerns that are least talked about and swept under the rug to avoid embarrassment. The stress of not getting an erection can cause anxiety and stress which worsens the condition and the vicious cycle continues. 

Erectile dysfunction is a natural part of aging and its prevalence increases with age. The Massachusetts Male Aging Study (MMAS) found that the incidence of erectile dysfunction in men between 40 and 70 years of age is around 52%. The study also concluded that roughly 50% of men at 50 years, 60% of men at 60 years, and 70% of men at 70 years of age had erectile dysfunction. Thus, nearly all the men who live long enough will develop ED at some part of their life (1).

Physiology of erection / How does erection work

The penis is the male copulatory organ made up of shaft and glans. The shaft of the penis contains three chambers, a pair of corpus cavernosa and corpus spongiosum, surrounded by fascial layers containing nerves, lymphatics, and blood vessels. The corpora cavernosa contains erectile tissues that act as a reservoir of blood, surrounded by a sheath of connective tissue with relatively low elasticity.

Image depicting the internal structure of the male penis

The corpus cavernosa contains muscle fibers, arteries, veins, and nerves. The inner surface of the corpus cavernosa looks like a sponge. An artery that supplies the blood, runs in the middle of each of corpus cavernosa which gives off numerous branches to form a network of vessels, whereas the veins draining them run in the enveloping connective tissue (2)

The urethra, a tube-like structure that delivers the semen and urine, runs through corpus spongiosum that lies in the undersurface of corpora cavernosa as shown in figure

Male sexual arousal is a complex process that involves the nerves, brain, emotions, and hormones. Penile erection is the first effect of male sexual stimulation. The physical stimulation of penile skin, especially glans’, sends sensory impulses to the brain that relay back to the penis in order to bring about an erection. Sexual arousal can also be due to seeing, listening, talking or even thinking about sex without any physical stimulus. Whether physical or psychological, sexual stimulation leads to erection and the degree of erection is proportional to the degree of stimulation. Erection is caused by parasympathetic signals that reach to the penis via pelvic nerves. They release nitric oxide and/or vasoactive intestinal peptide at their nerve endings. The nitric oxide especially relaxes the arteries of the penis, as well as relaxes smooth muscle fibers in the corpora cavernosa.

When the blood vessels in the penis receive signals from the brain, they dilate to open floodgates that cause a gush of blood to fill the corpora cavernosa. As the penile tissue starts filling up with each pulse, the veins that drain the penis get compressed, blocking the drainage. This makes the penis erect – and keeps it erect until the arteries keep supplying extra blood to penile tissues. Even the erection is intended to cease, the arteries constrict, decreasing the supply of blood to corpora cavernosa. This eases the pressure on compressed veins present in surrounding tissue, thereby increasing the venous drainage and outpouring the blood from the erect penis (3).

If there is a decrease in blood supply to the penis, the corpora cavernosa fail to fill up with enough blood required to cause an erection. In addition to that, the high pressure required to block the draining veins is not achieved, causing a continuous leak and flow back of blood.   

Image depicting the interior construction of the male penis.

(Obtained from Natural erectile dysfunction foundation)

Causes of Erectile Dysfunction

The cause of erectile dysfunction (ED) could lie anywhere in the nervous system, blood supply, hormones, and emotions. The mental stress and psychological issues are rather more ignored causes of erectile dysfunction. Low mood, depression, dispassionate behavior can all lead to erectile dysfunction. Sometimes, a combination of physical and psychological factors contribute to erectile dysfunction. 

Atherosclerosis

Atherosclerosis is the partial occlusion of blood vessels due to the formation of fatty plaque in the lumen of vessels. This leads to the narrowing of the arteries that supply the corpora cavernosa and a decrease in their blood supply. Thus, it becomes difficult to fill the corpora cavernosa to an extent that would cause a perfect erection. 

Diabetes

Peripheral neuropathy is one of the most common complications of diabetes mellitus. The sensory nerves in the penis start to malfunction, causing a reduced perception of physical contact with the penis, especially the glans. This causes decreased sexual stimulation and an inability to initiate an erection. Diabetes mellitus also causes dyslipidemia that contributes to atherosclerosis and further deteriorates the condition.

Obesity

Obesity along with diabetes is responsible for 8 million cases of erectile dysfunction. Obesity is a modern epidemic and a major contributor to erectile dysfunction. 79% of men presenting with erectile dysfunction have a BMI of 25 kg/m2 or greater. The incidence of erectile dysfunction is 1.5 times higher in men with BMI in the range of 25-30kg/m2 and is 3 times higher with BMI greater than 30kg/m2 (4)

Obesity causes dyslipidemia, diabetes, and heart diseases that lead to erectile dysfunction. The research evidence indicates that excessive body weight is an independent risk factor for erectile dysfunction and the risk increases with increasing BMI. Research has found that obesity is more potential cause of erectile dysfunction than aging. The lack of physical activity and hormonal imbalance in obese people are major contributors to this disorder.

High blood pressure

Hypertension and erectile dysfunction go hand in hand with each other. Both of these disorders share a common pathology i.e. endothelial dysfunction. Systemic hypertension can lead to the hardening of arteries. The blood flowing at a higher pressure leads through the vasculature causes the thickening of tunica media that narrows down the lumen of arteries supplying the viscera, including the penis. This deprives corpora cavernosa of an ample amount of blood required to cause an erection (5).

The antihypertensive medications given to control blood pressure are also a culprit here. The most prominent being the aldosterone receptor blockers (ARBs), thiazide diuretics, and the β-blockers (6).

Parkinson’s disease

Along with other non-motor symptoms of Parkinson’s disease (PD), erectile dysfunction remains to be one of the least talked about, yet significant. ED in men suffering from Parkinson’s not only reduced the quality of life but also takes away their confidence. The complications of PD such as tremors, rigidity, ‘clumsiness’ in fine motor control, and inability to initiate movements interfere with sexual drive. Other than medical interventions, appropriate psychotherapy and counseling relieve some of the factors contributing to ED including lubrication, reluctance to engage in sex, problems with ejaculation, and urinary incontinence (7).

Peyronie’s disease

In Peyronie’s disease, there is a development of scar tissue, called plaques, that can be felt through the skin. The plaques can cause softer or even painful erections due to loss of elasticity in the penis. The deposition of calcium at the plaque site causes them to get very hard and bend the penis to one side at a noticeable angle (8). The condition is treatable by medicine and/or surgery in certain cases. Some doctors recommend “wishful waiting” to have this go away on its own.

Tobacco use

Smoking has long been known for its adverse effects on health and life. Erectile dysfunction is one from the list. Smoking or tobacco use in the form of chewable gums, pills, and patches can cause damage to the innermost lining of the blood vessels. 

The research has found compelling evidence on the relationship between cigarette smoking and erectile dysfunction (9). In a study published in the American Journal of Epidemiology, 2115 men were evaluated to probe the risk of developing erectile dysfunction in the general population versus smokers. The research data indicated that the incidence of erectile dysfunction is twice as common in smokers versus the people who don’t smoke at all (10)

The good news though is that as soon as you quit smoking, the vessels tend to improve and repair the damage. But if that’s not the case, consultation with a doctor and a multidisciplinary approach are aimed to treat erectile dysfunction.

Drug abuse

Recreational drugs not only include illegal drugs but also prescription drugs that are misused. Using drugs recreationally can alter the way your body functions and can sometimes cause serious damage.

The drugs notorious for harming sexual health are listed below along with their mechanism of causing damage (11)

  • Cocaine, Amphetamines can cause arteries supplying the corpora cavernosa to narrow, preventing enough blood from reaching the inside the penis.
  • Barbiturates,  whose both legal and illegal misuse, may decrease interest in sex
  • Nicotine excess can decrease sexual desire
  • Marijuana causes spasm of smooth muscle in the penis and prevents them from relaxing, thus limiting the influx of blood.
  • Heroin interferes with the level of testosterone in the blood, causing decreased sexual drive and loss of interest in sex.

Alcohol abuse can greatly affect the reproductive system of the man. It not only interferes with the level of sexual hormones in the blood but also causes damage to cells in the penis and testis. If you’re drinking a lot and have problems with getting or maintaining an erection, consider dropping this habit and consult a doctor.

Medications

Certain medication given to treat medical conditions can lead to erectile dysfunction.

Type of DrugGENERIC AND BRAND NAMES
Diuretics and high blood pressure drugsHydrochlorothiazide  Chlorthalidone (Hygroton)Triamterene (Maxide, Dyazide)Furosemide (Lasix)Bumetanide (Bumex)Guanfacine (Tenex)Methyldopa (Aldomet)Clonidine (Catapres)Verapamil (Calan, Isoptin, Verelan)Nifedipine (Adalat, Procardia)Hydralazine (Apresoline)Captopril (Capoten)Enalapril (Vasotec)Metoprolol (Lopressor)Propranolol (Inderal)Labetalol (Normodyne)Atenolol (Tenormin)Phenoxybenzamine (Dibenzyline)Spironolactone (Aldactone) 
Antidepressants, anti-anxiety drugs, andantiepileptic drugsFluoxetine  (Prozac)Tranylcypromine (Parnate)Sertraline (Zoloft)Isocarboxazid (Marplan)Amitriptyline (Elavil)Amoxapine (Asendin)Clomipramine (Anafranil)Desipramine (Norpramin)Nortriptyline (Pamelor)Phenelzine (Nardil)Buspirone (Buspar)Chlordiazepoxide (Librium)Clorazepate (Tranxene)Diazepam (Valium)Doxepin (Sinequan)Imipramine (Tofranil)Lorazepam (Ativan)Oxazepam (Serax)Phenytoin (Dilantin
Anti-HistaminesDimenhydrinate (Dramamine)Diphenhydramine (Benadryl)Hydroxyzine (Vistaril)Meclizine (Antivert)Promethazine (Phenergan)
NSAIDsNaproxen  (Anaprox, Naprelan, Naprosyn)Indomethacin (Indocin)
Parkinson’s disease medicationsBiperiden (Akineton)Benztropine (Cogentin)Trihexyphenidyl (Artane)Procyclidine (Kemadrin)Bromocriptine (Parlodel)Levodopa (Sinemet)
AntiarrhythmicsDisopyramide  (Norpace)
Histamine H2-receptor antagonistsCimetidine  (Tagamet)Nizatidine (Axid)Ranitidine (Zantac)
Muscle relaxantsCyclobenzaprine  (Flexeril)Orphenadrine (Norflex)
Anti Cancer drugsFlutamide  (Eulexin)Leuprolide (Lupron)Busulfan  (Myleran)Cyclophosphamide (Cytoxan)

*Obtained from WebMD with permission and link to the source (12)

Sleep disorders

Sleep is considered to be “the third pillar of health” along with diet and exercise. Insufficient sleep, insomnia, obstructive sleep apnea, restless leg syndrome, and work shift disorder are all examples of sleep disorders. The research evidence indicates that insufficient sleep is linked to poor sexual performance and an inability to maintain an erection (13).

For example, in obstructive sleep apnea, the quality of sleep is reduced and the level of testosterone in blood takes a dive. There is a decreased level of oxygen in the blood and increased acidosis. Both the testosterone and oxygen are required for an erection which eventually cannot occur in the absence of these. A 2016 study found the prevalence of erectile dysfunction in people suffering from sleep apnea to be as high as 63% (14).

An old saying is “A healthy brain is in a healthy mind”. Sleep disorders can affect brain health and can thus cause a lack of interest, reduced sexual drive, and irritability. The stress of not sleeping well at night and the anxiety of being suffering from disorders also need addressing to treat erectile dysfunction. 

Pelvic injuries

The sensory supply of the penis is from a branch of the pudendal nerve that runs its course in the pelvic bone. Fracture of the pelvis can damage the pudendal nerve and lead to a complete loss of sensations from the penis. The fracture of symphysis pubis – middle joint of both pelvic bones where the shaft of the penis is attached – is also a major cause of sexual dysfunction resulting after pelvic injuries (15)

A study done to find a link between pelvic fractures and erectile dysfunction found its incidence is up to 46% of studied subjects. Another study concluded the impairment of sexual function in up to 61% of people with pelvic fractures (16).   

Prostate Cancer

The prostate is a walnut-sized gland located behind the pubic symphysis between the bladder and penis. It is the part of the male reproductive system and is involved in nourishment and protection of sperm. Having prostate cancer is one of the most dreadful diagnoses one can hear from a doctor. Cancer doesn’t directly cause erectile dysfunction rather the treatment regimen for cancer results in erectile dysfunction. Not to forget the psychological stress and depression that comes in most of such cases that add fuel to the fire. 

The hormonal treatment for prostate cancer lowers the level of testosterone in the blood which, as stated earlier, lead to reduced sex drive and loss of interest in sex. Radiotherapy done for prostate cancer can also lead to erectile dysfunction but the condition is quite reversible (17)

Surgical interventions for prostate cancer have a high risk of erectile dysfunction. The severity of erectile dysfunction depends on the stage of cancer, type of surgery, and skill of the surgeon. Erectile dysfunction after complete removal of the prostate have varying prognosis depending on patient age, whether the surgeon preserved the neurovascular bundle or not, and preoperative erectile status. 

Surgery

Erectile dysfunction is a well-established complication of prostate and bladder surgery. Damage to nerves supplying the urinary and genital system can result in incontinence and impotence respectively. The outcome of such surgical procedure depends on the factors explained above. 

Different surgical procedures have different incidence rates of erectile dysfunction and recovery. For example, recovery from erectile dysfunction occurs in 68% of men treated with bilateral nerve-sparing surgery and in 47% of those treated with unilateral nerve-sparing surgery (18).

Diagnosis 

To diagnose erectile dysfunction, your doctor will take a detailed history, examination and order some lab tests to make a complete diagnosis 

History

This is the most important and uncomfortable component in diagnosing erectile dysfunction. 

Your doctor will ask personal questions about your sexual health and whether you’re able to satisfy your partner or not. Some fertility clinics have questionnaires that are handed to clients to remove the element of embarrassment or inability to explain the problem. The questions might include 

  • Are you able to get an erection? 
  • Can you maintain an erection until your partner receives an orgasm? 
  • How hard is your erection? Is it sufficient to cause penetration? 
  • Do you feel pain while getting an erection? 
  • Is your partner satisfied after intercourse?
  • Do you feel your penis to have deviated on one side when it erects? 
  • Do you feel numbness, tingling or no sensations from the penis at all?
  • Are you suffering from any heart disease, diabetes mellitus, hypertension, or any other chronic disease? 
  • Have you had any previous surgeries?
  • History of prostate cancer? Any treatment is taken for it?
  • Any medications are currently taking or have taken in the past? 
  • Are you a smoker? 
  • Any addiction to drugs or other substances?
  • Are you happy with your lifestyle and sex life?
  • Do you feel low, have little to no motivation in life, or anxious?
  • How many hours of sound sleep you have every day?

Examination

After a complete and thorough history, the next step in diagnosing erectile dysfunction is an examination of genitals. The blood pressure will be checked. Your doctor will then take you to an examination room after informed consent and will examine you to look for any pathologies. He will inspect and palpate for

  • Any scar or plaques to rule out Peyronie’s disease
  • Intact sensations especially at glans in case of peripheral neuropathy
  • Any signs of perineal or pelvic surgery
  • Pelvic fracture and involvement of perineal nerves
  • Testicular atrophy

Laboratory investigations

In certain circumstances, the physician might order some blood tests to evaluate the hormonal status, diabetes, serum profile. These laboratory investigations include:

  • Fasting blood sugar and HbA1Cto confirm diabetes mellitus
  • Testosterone, prolactin, and luteinizing hormone
  • Certain drug levels if you’re on medications

To check the flow of blood in vessels bringing and taking away blood from the penis, the doctor might request a Doppler ultrasound study. Like a normal ultrasound scan that produces two-dimensional images, a doppler ultrasound produces colored three-dimensional images that help the doctor diagnose any blood flow problems

Treatment 

There are various treatment options available for erectile dysfunction. Neither all of them are equally efficacious nor each one is for everyone. The choice of treatment given depends on the underlying cause of erectile dysfunction, the duration of disease, whether previous treatments were successful or not. Consult your doctor first before jumping on to a treatment regimen of your own. 

Lifestyle changes

The first and most important step in treating erectile dysfunction is lifestyle changes. Some of the personal habits that can cause erectile dysfunction should be left first before moving on to medical treatment. If you have erectile dysfunction, you should consider to

  • Quit smoking
  • Minimize or completely stop alcohol intake
  • Stop using illicit drugs
  • Increase physical activity
  • Exercise regularly
  • Eat healthily

These interventions, though sound nominal, can have a great impact on sexual life and could be the only thing needed to treat erectile dysfunction.

Psychotherapy

As stated before, psychological factors are as common a cause of erectile dysfunction as physical factors. Erectile dysfunction due to anxiety, stress, depression, low mood, insomnia, and other psychological reasons need counseling to help such couples. 

Oral medications

The following four oral medications have shown to improve erectile dysfunction in most of the men. These include

  1. Sildenafil (Viagra)
  2. Tadalafil (Adcirca, Cialis)
  3. Vardenafil (Levitra, Staxyn)
  4. Avanafil (Stendra)

These drugs increase the release of nitric oxide, a chemical messenger substance responsible for dilation of arteries, which results in an increased influx of blood into the corpora cavernosa. One thing to be noted here is that these drugs don’t cause sexual stimulation directly rather potentiate the sexual excitement and cause erections to become harder than before. 

Since they dilate the blood vessels, these drugs are contraindicated in patients with cardiovascular diseases and hypotension.

Injection therapy

Alprostadil is licensed for use in erectile dysfunction. This drug also expands blood vessels with a different mechanism. Due to its potent effects, it is given locally and cannot be given systemically. Alprostadil injections are self-administered at the base or side of the penis and results in stronger and harder erections. Alprostadil suppositories are also available which are kept inside the penile urethra to increase blood supply and get a harder erection.

Side effects of alprostadil use include pain at the injection site, allergic dermatitis, itching, prolonged erection, and scarring.

Trimix injections contain a combination of three drugs i.e. alprostadil, papaverine, and phentolamine. These self-administered injections can bring about erection in 15-20 mins (19). Some physicians prefer combination therapy of Trimix and oral sildenafil because of better results and harder erections. A study on 80 patients with erectile dysfunction found the synergic action of these drugs increases the blood flow to corpora cavernosa to an extent not achieved by any of these two alone (20)

Penile pumps

The penile pumps are vacuum pumps that are applied to the penis and suck air to create a vacuum inside the tube. The vacuum pulls the penis erect and blood fills the inside chambers on the penis to maintain an erection for a time sufficient to have an intercourse. The erection can further be prolonged by applying a ring device or clamp to the base of the penis. 

Surgery

The surgical intervention is rarely needed in case of erectile dysfunction. Yet, the treatment modality exists to increase your chances of getting harder erections. Surgery is generally used to:

  • Implant a prosthetic device within the penis, which causes an erection.
  • Reconstruct and increase the arterial supply of the penis to cause harder erections.
  • Block veins that drain the penis which helps to maintain an erection.

Conclusion

Erectile dysfunction (ED) is a common cause of sexual dissatisfaction among couples. The clinically reported cases of ED are just the tip of the iceberg whereas the main disease burden remains unreported due to problems with expressing sexual difficulties and stigma of being less manly. Nevertheless, most cases of erectile dysfunction are treatable with appropriate counseling and lifestyle changes. Consultation with a doctor is needed before starting any medicine. Surgery remains the last resort for resistant cases. Modern medicine combinations are now available (such as trimix) with really promising results and client satisfaction. 

References

  1. https://pmj.bmj.com/content/93/1105/679
  2. https://emedicine.medscape.com/article/1949325-overview
  3. https://webmd.com/erectile-dysfunction/how-an-erection-occurs
  4. https://www.ncbi.nlm.nih.gov/pubmed/24720114
  5. https://www.ncbi.nlm.nih.gov/pubmed/22240443
  6. https://www.ncbi.nlm.nih.gov/pubmed/26049386
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229252/
  8. https://www.ncbi.nlm.nih.gov/pubmed/12494281
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485976/
  10. http://aje.oxfordjournals.org/content/161/4/346.long
  11. https://www.ncbi.nlm.nih.gov/pubmed/18093094
  12. https://www.webmd.com/erectile-dysfunction/guide/drugs-linked-erectile-dysfunction
  13. https://www.ncbi.nlm.nih.gov/pubmed/30209897
  14. https://www.ncbi.nlm.nih.gov/pubmed/26758960
  15. https://www.ncbi.nlm.nih.gov/pubmed/26764545
  16. https://www.ncbi.nlm.nih.gov/pubmed/17693842
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623527/
  18. https://www.ncbi.nlm.nih.gov/pubmed/12755991
  19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2448319/
  20. https://www.ncbi.nlm.nih.gov/pubmed/18476965

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