The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.

Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and the medications used to treat them. Aspects of an ageing man’s lifestyle and behaviour and androgen deficiency, most often decreasing testosterone levels, may affect sexual function as well. A study of men between the ages of 30 and 79 years showed that 24% had testosterone levels below 300 ng/dL and 5.6% had symptomatic androgen deficiency.2

A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically.

There have been some studies to suggest that a placebo effect that improves ED may work for some men. One study found that men taking an oral placebo pill showed as much improvement in ED symptoms as men who took actual medication to improve ED. Conversely, men who were given therapeutic suggestions to improve ED did not see signs of symptom improvement.
VED involved placing the penis in a clear plastic tube where negative pressure created by the vacuum pump leads to penile engorgement and tumescence. Usually a constriction ring can be placed on the base of penis following penile engorgement. Some men complain of bruising, a “cold” penis and pain associated with the constriction ring; however, in some men with NED sensation may not be intact mitigating the side effects of VEDs. VEDs have reported effectiveness up to 90% in certain ED populations and it remains a non-invasive means to achieve and erection.

The association of CVD and ED was noted in 1997 as one analysed the results of the MMAS. In this landmark study, 1709 men aged 40–70 years were enrolled between 1987 and 1989. A follow-up some 10 years later revealed a striking relationship between ED and CVD. In this study, it became clear that the risk factors for ED were very similar to those of CVD, such as diabetes mellitus, smoking and dyslipidaemia.18
Intraurethral therapy (Medicated Urethral System for Erections, or MUSE): Alprostadil (PGE1) has been formulated into a small suppository that can be inserted into the urethra (the canal through which urine and semen are excreted). The suppository is preloaded into a small applicator and by placing the applicator into the tip of the penis and compressing the button at the other end of the applicator and wiggling the applicator, the suppository is released into the urethra. Gentle rubbing/massaging of the penis will cause the suppository to dissolve and the medication is absorbed through the urethra and passes into the penis where it stimulates the relaxation of the muscle in the arteries and increases blood flow to the penis. It takes 15 to 30 minutes for this to occur. Success rates in the clinical studies were noted to be about 65%, however lower rates were noted when it started being used in the real world setting. This drug may be effective in men with vascular disease, diabetes, and following prostate surgery. This is a useful alternative for men who do not want to use self-injections or for men in whom oral medications have failed. Few side effects occur. The most common side effect is penile pain, which can vary from minor to uncomfortable. MUSE use has been associated with lowering of the blood pressure and thus it is recommended that the first time using the MUSE be in the physician's office so that you can be monitored. One cannot use lubricants of any type to help with the insertion of the applicator thus to make it easier to insert you should urinate immediately before using the MUSE system as this will lubricate the urethra. A temporary tourniquet is often helpful in allowing the medication to stay in the erectile tissue a little longer and seems to give a somewhat better response.
Erythrocytosis has been noted in men on TRT, and should be monitored every 6–12 months depending upon the patients’ response to changes in haematocrit levels. For mild elevations, the dosage of testosterone can be decreased or the interval of using the medication can be increased. With the haematocrit greater than 50%, decisions to temporarily discontinue the medication or periodic phlebotomy may be indicated.38
Similar to heart-disease-related to atherosclerosis (plaque formation within the blood vessels), the concept of bypassing or angiographically dilating and stenting penile arteries has been entertained recently with improvements in microvascular surgery and interventional radiology. However, the main drawback with most erectile dysfunction is the failure of vascular relaxation within the corpora cavernosa rather than the one feeding penile artery. Stenting or surgical grafting to bypass a blockage would be ideal for a single obstruction site along a penile artery. Because most erectile dysfunction pathology resides within the sponge-like vascular plexus of the penis, the ability of diffusely dilating and expanding the many vascular chambers of the penis is difficult to impossible. As such, unless the situation is that the penile artery was injured during a pelvic trauma, and the potential to bypass another vessel into the single penile artery, the concept of vascular reconstruction or angio-radiology stenting has very low yield.
Intraurethral therapy (Medicated Urethral System for Erections, or MUSE): Alprostadil (PGE1) has been formulated into a small suppository that can be inserted into the urethra (the canal through which urine and semen are excreted). The suppository is preloaded into a small applicator and by placing the applicator into the tip of the penis and compressing the button at the other end of the applicator and wiggling the applicator, the suppository is released into the urethra. Gentle rubbing/massaging of the penis will cause the suppository to dissolve and the medication is absorbed through the urethra and passes into the penis where it stimulates the relaxation of the muscle in the arteries and increases blood flow to the penis. It takes 15 to 30 minutes for this to occur. Success rates in the clinical studies were noted to be about 65%, however lower rates were noted when it started being used in the real world setting. This drug may be effective in men with vascular disease, diabetes, and following prostate surgery. This is a useful alternative for men who do not want to use self-injections or for men in whom oral medications have failed. Few side effects occur. The most common side effect is penile pain, which can vary from minor to uncomfortable. MUSE use has been associated with lowering of the blood pressure and thus it is recommended that the first time using the MUSE be in the physician's office so that you can be monitored. One cannot use lubricants of any type to help with the insertion of the applicator thus to make it easier to insert you should urinate immediately before using the MUSE system as this will lubricate the urethra. A temporary tourniquet is often helpful in allowing the medication to stay in the erectile tissue a little longer and seems to give a somewhat better response.
Modern drug therapy for ED made a significant advance in 1983, when British physiologist Giles Brindley dropped his trousers and demonstrated to a shocked Urodynamics Society audience his papaverine-induced erection.[35] The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, and orally effective drug therapies.[36][better source needed][37][better source needed]
Psychological factors — Psychological issues such as depression, anxiety, guilt or fear can sometimes cause sexual problems. At one time, these factors were thought to be the major cause of impotence. Doctors now know that physical factors cause impotence in most men with the problem. However, embarrassment or "performance anxiety" can make a physical problem worse.
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
In this study, ED proceeded CVD in almost 70% of cases. Similarly, many men with ED have been found to have pre-existing CVD. A study by Vlachopoulos et al evaluated the incidence of asymptomatic CVD in 50 men with ED.22 These authors found that 19% of men with ED had asymptomatic CVD. Similarly, Mulhall and colleagues found that 20% of men presenting with ED and vascular insufficiency on penile duplex had asymptomatic CVD.23
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Achieving an erection is a complicated process, requiring transmission of sensations from the genital area to the nervous system and the return of nervous impulses to the muscles and blood vessels of the penis. Anything that interferes with this interchange, such as disease or injury of the blood vessels, muscles, or nerves, can make achieving and maintaining an erection difficult. Psychological factors, such as anxiety and depression, can also interfere with erectile function. Anxiety and depression may also develop as a consequence of impotence.

Prevention of some of the causes that contribute to the development of erectile dysfunction can decrease the chances of developing the problem. For example, if a person decreases their chances of developing diabetes, heart disease, and hypertension, they will decrease their chances of developing erectile dysfunction. Other things like stopping smoking, eating a healthy diet (heart healthy with adequate vitamin intake), and exercising daily may reduce a person's risk.
Their treatment plan will include a great deal of information about ED. It is important you take the time to read it all. You will be better prepared to manage your condition as a partner—and not just a patient. Also, erectile dysfunction is often a symptom of a more serious underlying condition—like heart disease, diabetes, high blood pressure, or even depression. That’s why we want you to learn as much as you can. Nothing would be a sign of our success more so then if you could resolve the condition that causes your ED instead of needing to use the medications your doctor prescribes. We strongly recommend optional laboratory tests. You do not need to get them to receive treatment but it can be one of the best things you can do for your health in the long run.

The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. [10]
PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73). Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. Zesiewicz et al., performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).
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Traditionally, erectile impotence (the classical definition of impotence) is the failure to achieve penile erection during intercourse. It may have either physical or psychological causes. Alcoholism, endocrine disease, and neurological disorders are typical physical causes. Psychological causes include anxiety over performance, hostility or other negative feelings toward the sexual partner, and stress, anxiety, depression, or other emotional conflicts outside of the relationship. Erectile impotence occasionally occurs with age and, although attributed by the individual to the aging process itself, it is usually secondary to disorders of aging, such as faulty blood circulation or prostate disease. In cases of impotence caused by blood vessel dysfunction, an insufficient supply of blood flows into the penis, or the blood diffuses out into adjacent tissues.
Cardiovascular diseases: The most common cause of cardiovascular diseases in the United States is atherosclerosis, the narrowing and hardening of arteries that reduces blood flow. Atherosclerosis (a type of vascular disease) typically affects arteries throughout the body; hypertension, high blood cholesterol levels, cigarette smoking, and diabetes mellitus aggravate atherosclerosis. Hardening of the arteries to the penis and pelvic organs, atherosclerosis, causes insufficient blood flow into the penis. There is a close correlation between the severity of atherosclerosis in the coronary arteries and erectile dysfunction. For example, men with more severe coronary artery atherosclerosis (hardening of the arteries in the heart) also tend to have more erectile dysfunction than men with mild or no coronary artery atherosclerosis. Some doctors suggest that men with new onset erectile dysfunction undergo evaluation for silent coronary artery diseases (advanced coronary artery atherosclerosis that has not yet caused angina or heart attacks).
Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.
Occasional successful sexual function and early morning erections do not preclude the possibility of endocrine dysfunction. Since abnormally low levels of testosterone frequently are the primary cause of impotence, it is recommended that determination of the blood level of testosterone be an integral part of the total evaluation of the impotent patient.

The medications are extremely effective, which is very good. And the medications are, for the most part, extremely well-tolerated. But there are, like with any medications, a potential downside. The one absolute downside to the use of any of these erection what we call PDE5 medications is if a patient is using a nitroglycerin medication. And nitroglycerins are used for heart disease and for angina, for the most part, although there are some recreational uses of nitrites. And that’s important because your blood vessels will dilate and your blood pressure will drop. And that is an absolute contraindication.


Penile prostheses are very effective, and most patients who have a prosthesis placed are satisfied with the prosthesis. However, placement of a prosthesis causes scarring of the tissue within the corpora cavernosa, and if the prosthesis requires removal, other forms of therapy, except for the vacuum device, are often not effective. Thus, most physicians reserve placement of a prosthesis for men who have tried and failed or have contraindications to other therapies.
ED can also occur as a side effect of some medications, for example some high blood pressure medications such as certain diuretics and beta blockers. If you think that a medication you are taking has a negative effect on your sex life, you should discuss this with your prescribing doctor. Your doctor may be able to recommend an alternative treatment.

When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis.


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Implantable penile prostheses are usually considered a last resort for treating impotence. They are implanted in the corpora cavernosa to make the penis rigid without the need for blood flow. The semirigid type of prosthesis consists of a pair of flexible silicone rods that can be bent up or down. This type of device has a low failure rate but, unfortunately, it causes the penis to always be erect, which can be difficult to conceal under clothing.
The recommended starting dose of tadalafil for use as needed for most patients is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher to 20 mg or lower to 5 mg depending on efficacy and side effects. Doctors recommended that patients take tadalafil no more frequently than once per day. Some patients can take tadalafil less frequently since the improvement in erectile function may last 36 hours. Patients may take tadalafil with or without food. Tadalafil is currently the only PDE5 inhibitor that is FDA-approved for daily use for erectile dysfunction and is available in 2.5 mg or 5 mg dosages for daily use.
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

In the Massachusetts Male Aging Study (MMAS) among a community-based survey of men aged 40-70 years, 52% of the men reported some degree of erectile difficulty. Complete ED, defined as the total inability to obtain or maintain suitable erections during sexual stimulation, as well as the absence of nocturnal erections (normal erections [four to six/night], which occur during sleep), occurred in 10% of the men in the study. Lesser degrees of mild and moderate ED occurred in 17% and 25% of participants.
The first line and by far the most common treatment today is with the prescription drug sildenafil citrate, sold under the brand name Viagra. An estimated 20 million prescriptions for the pill have been filled since it was approved by the FDA in March 1998. It is also the most effective treatment with a success rate of more than 60%. The drug boosts levels of a substance called cyclic GMP, which is responsible for widening the blood vessels of the penis. In clinical studies, Viagra produced headaches in 16% of men who took it, and other side effects included flushing, indigestion, and stuffy nose.
Injection therapy: The modern age of such drug therapies began in 1993 when the injection of papaverine (Pavabid), an alpha-blocker that produces vasodilatation (widening of the blood vessels), was shown to produce erections when injected directly into the penis. Soon afterward, other vasodilators, such as prostaglandin E1 (PGE 1) monotherapy (Caverject, Edex), PGE1 and phentolamine (Regitine), and Trimix (papaverine, phentolamine and prostaglandin E1), were demonstrated to be effective. The benefit of combination therapy is the decreased dosing of each with less side effects. Most important is the reduction of the prostaglandin PGE1 dosing, which is associated to the localized pain.
The Food and Drug Administration (FDA) does not recommend alternative therapies to treat sexual dysfunction.[27] Many products are advertised as "herbal viagra" or "natural" sexual enhancement products, but no clinical trials or scientific studies support the effectiveness of these products for the treatment of ED, and synthetic chemical compounds similar to sildenafil have been found as adulterants in many of these products.[28][29][30][31][32] The FDA has warned consumers that any sexual enhancement product that claims to work as well as prescription products is likely to contain such a contaminant.[33]
Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
Infection is a concern after placement of a penile prosthesis and is reported as a complication in up to 20% of men undergoing placement of a penile prosthesis. If the device becomes infected more commonly, it needs to be removed. Another prosthesis can be placed after the infection is treated and the penile tissues have healed, but it is a difficult surgery. Erosion of the prosthesis, whereby it compresses through the corporal tissue, into the urethra may occur. Symptoms include pain, blood in the urine, discharge, abnormal stream, and malfunction of the prosthesis. If the prosthesis erodes, it will need to be removed. A catheter is placed to allow the urethra to heal.

…that relieve erectile dysfunction (impotence) in men. Two common commercially produced PDE-5 inhibitors are sildenafil (sold as Viagra) and vardenafil (Levitra). PDE-5 inhibitors work by blocking, or inhibiting, the action of phosphodiesterase-5 (PDE-5), an enzyme naturally present in the corpus cavernosum, the spongy erectile tissue of the penis. Under…
If you are taking medications (alpha-blockers) for problems with an enlarged prostate, you should discuss your prostate medications with your doctor. Alpha-blockers also can cause lowering of the blood pressure. Thus your doctor will need to carefully watch your blood pressure when you start the PDE5 inhibitor. Common alpha-blockers include doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax).

When other treatments haven’t helped, a penile implant may be the right solution. A penile implant is a medical device that is surgically placed into a penis to mimic the look and performance of a natural erection9. Implants are custom-fitted to your anatomy. Sensitivity and the ability to ejaculate aren’t typically affected either, so you’ll be able to have an orgasm normally (unless you have a medical condition that prevents this)7.
The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.

Psychosexual counselling, or sex therapy, is an appropriate recommendation especially for men who are experiencing discord with their partner especially if the conflict is related to the man’s ED. Counselling usually consists of 5–20 sessions with counsellor. It is our recommendation that referral doctors treating men with ED make a referral to a psychotherapist or sex therapist who is certified by AASECT (American Association of Sexuality Educators, Counselors and Therapists) of certified sexuality educator.43
When we say it’s a barometer of men’s health, it’s a signal. It’s an indicator that things may be right or not. And so when a man develops an erectile problem– and we’re talking about something that is occurring over time. It’s not something that just occurred overnight. When it occurs overnight, it’s more often than not a psychogenic, an anxiety reaction.
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