The pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
The recommended starting dose of vardenafil is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher or lower depending on efficacy and side effects. The maximum recommended dose is 20 mg, and the maximum recommended dosing frequency is no more than once per day. Patients can take vardenafil with or without food. As with sildenafil, for vardenafil to be effective, sexual stimulation must occur.

If PDE-5 inhibitors are not suitable or don’t work, other therapies include injections into the base of the penis, which cause flow of blood into the penis and a fairly immediate erection that lasts around an hour. The drugs injected are alprostadil (Caverject and Erectile dysfunctionex) and Invicorp (VIP and phentolamine). Alprostadil may also be inserted as a gel into the opening of the penis. This is not suitable if your partner is pregnant.


Instead of injecting a medicine, some men insert a suppository of alprostadil into the urethra. A suppository is a solid piece of medicine that you insert into your body where it dissolves. A health care professional will prescribe a prefilled applicator for you to insert the pellet about an inch into your urethra. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes.
The surgery for placement of a penile prosthesis is typically an outpatient surgery. Doctors often perform a penile prosthesis through a single incision, and all of the components are hidden under the skin. Health care professionals often give patients antibiotics at the time of surgery and often after the surgery to decrease the risk of developing an infection. Depending on your health history, a health care provider may leave a catheter in your penis to drain your bladder overnight.
Men who do not respond or tolerate oral medications are best treated with an internal penile pump (IPP) commonly known as an inflatable implant. The Internal Penile Pump is an inflatable, water-filled device. During the course of a 45-minute outpatient procedure, the pump is inserted through a one-inch opening in the scrotal sac. By squeezing the pump, (which is contained completely within the scrotum), for approximately a minute, fluid is pumped into the penis, resulting in a long lasting erection. To return the penis to its flaccid state, simply press and hold down the pump. Once inserted, there is no maintenance required for the pump, which can remain in place for a lifetime. Couples are once again able to have spontaneous sex. Normal sensation including orgasm and ejaculation are not affected.
MSA is a neurodegenerative disease of undetermined etiology, where ED is an early prominent sign occurring in 40% of men at the time of diagnosis (46,47). ED occurs in the majority of patients and the exact cause of it is unknown (48). Like PD, MSA likely affects the dopaminergic pathways within the brain essential for arousal (49). Orthostatic hypotension (OH) as a causal factor has been refuted by evidence that sildenafil can overcome reduced filling pressures, and the ED usually precedes the development of OH (46,49,50). Similar to other neurologic disorders that lead to ED, other disease related factors such as psychosocial stress, the burden of chronic illness, changed appearance, fatigue, decreased fine motor movement of fingers, immobility and diminished self-esteem due to loss of independence may contribute as well (51).

The great majority of ED cases in diabetic men have a physical cause, such as neuropathy or circulatory problems. In some cases, however, the cause of ED is psychological, including depression, guilt, or anxiety. With a thorough exam, the doctor should be able to determine whether the ED is psychological or physical in nature. If the cause is psychological, your doctor may refer you to a psychiatrist, psychologist, sex therapist, or marital counselor. Do not view such a diagnosis as an insult. Most psychologically-based ED is easily and successfully treated.
Approximately 95% of penile implant surgeries are successful in producing erections that enable men to have sexual intercourse. Moreover, patient satisfaction questionnaires show that up to 90% of men who have undergone penile implants say they would choose the surgery again, and overall satisfaction ratings are higher than those reported by men using oral medication or penile injection therapy.
In some cases, however, these drugs may be unsuitable for patients with heart disease. If you are considering one of these drugs and you have heart disease, as many diabetics do, be sure to tell your doctor. In rare cases, the pills may create “priapism,” a prolonged and painful erection lasting six hours or more (although reversible with prompt medical attention).
The Prostate Cancer Prevention Trial was a landmark study by Thompson et al that prospectively assessed the time to developing CVD after the diagnosis of ED. There were 4247 men with no ED at study entry; 2420 developed incident ED (defined as the first report of ED of any grade) over 5 years. Those men that developed ED had a 1.45-fold higher probability of experiencing a CV event compared with men who did not develop ED.27

If you have symptoms of ED, it’s important to check with your doctor before trying any treatments on your own. This is because ED can be a sign of other health problems. For instance, heart disease or high cholesterol could cause ED symptoms. With a diagnosis, your doctor could recommend a number of steps that would likely improve both your heart health and your ED. These steps include lowering your cholesterol, reducing your weight, or taking medications to unclog your blood vessels.


Having erection trouble from time to time isn't necessarily a cause for concern. If erectile dysfunction is an ongoing issue, however, it can cause stress, affect your self-confidence and contribute to relationship problems. Problems getting or keeping an erection can also be a sign of an underlying health condition that needs treatment and a risk factor for heart disease.
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