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Even if the scores from one group can be transferred to the other, the 52% figure is still deceptive because it doesn't differentiate ED by age.

In the MMAS, 40% of 40-year-old men had ED, including 17% who were only minimally impotent, whereas 67% of 70 year olds were impotent. Moreover, not all studies are in agreement with these figures. Analysis of data from the US National Health and Social Life Survey indicates that among men 50–59 years old, 18% complained of trouble achieving or maintaining an erection during the past year [ 4]. A survey in the Netherlands found that only 1% of men 50–65 years of age had a complete inability to achieve an erection, and it was only in men aged 70–78 years that the rate of ED was similar to that in the MMAS [ 5]. Out of 13 studies on the prevalence of ED that were published until June 1998, the MMAS results were among the highest [ 1]. Thus, Pfizer's statement that “more than half of all men over 40 have difficulties getting or maintaining an erection” does not reflect the large variation in the prevalence of ED found in different studies.

The MMAS found a strong association between ED and psychological factors, including “depression, low levels of dominance, and anger either expressed outward or directed inward.” The authors suggested that psychological symptoms might be a cause of ED, but these symptoms could also be an effect of ED (they wrote that “a man who has experienced a recent pattern of ED may be expected to be anxious, depressed and lacking self-esteem and self-confidence”) [ 2]. While not to deny that there is an association between ED and psychological symptoms, once again the MMAS may be an outlier. In the Dutch study previously mentioned, only one-third of all men and only 20% of men over the age of 70 with significant ED had major psychological concerns. Furthermore, in sexually active men, 17%–28% had no normal erections, indicating that full erectile function is not essential for sexual functioning [ 5]. Only 20% of Japanese men 40 to 79 years of age reported more than little worry and concern about sexual functioning, suggesting that perceptions of elderly male sexual function and its impact on health-related quality of life may differ among cultures and ethnic groups with differing values [ 6].

On its Web site, Pfizer states: “VIAGRA can work for you.

In fact, studies show that VIAGRA works for more than 80% of men with ED taking VIAGRA 100 mg versus 24% of men taking a sugar pill” ( http://www.viagra.com/whyViagra/highlyEffective.asp). The 80% success rate that Pfizer quotes for Viagra is important, though not critical, to being able to promote its use to a wide variety of men. But that number is qualified on the Pfizer Web site as the number who experience improved erections ( http://www.viagra.com/consumer/aboutViagra/index.asp). It is open to speculation whether the goal of most men is improved erections, or successful intercourse and the achievement of an orgasm.

In most studies on Viagra, a 50%–60% rate of successful intercourse is recorded (in the dose titration studies reviewed in [ 1] for patients taking placebo, up to 25% of attempts at intercourse were successful compared with 50%–60% for patients taking Viagra 25–100 mg). This 50%–60% rate is far short of the “more than 80% of men” that Pfizer trumpets.

To make Viagra into a lifestyle drug, Pfizer needs to convince men that it is the first choice for therapy for any degree of ED, whatever the genesis of the problem.

However, drug therapy may not always be the most appropriate treatment option. The National Health and Social Life Survey data indicate that emotional and stress-related problems such as a deteriorating social and economic position generate elevated risk of experiencing sexual difficulties.

In these cases, Viagra may be less important than counseling or help in finding a new job.

These possibilities are never mentioned on the Viagra Web site. Here is a sample of the questions and answers on the “About ED” portion of the Web site: Question: “I don't have ED because the problem doesn't happen often.

Does this mean that VIAGRA is not for me?” Answer: “Even if erection problems happen only once in a while, VIAGRA can help. You should know that most men with ED only experience problems some of the time.

In one study, VIAGRA helped 87% of men

with

In case the message is missed, there is a couple on the Web page where the man looks to be in his mid-to-late 30s. Pfizer reinforces its message with direct-to-consumer magazine ads, such as one featuring a virile looking man around 40 saying, “A lot of guys have occasional erection problems. I chose not to accept mine and asked about Viagra.” Drug companies have identified lifestyle drugs as a “growth market.” The initial television ads in the US for Viagra used an aging Bob Dole (born 1923) as a spokesman, a 1996 Republican presidential candidate.

Since then, Pfizer has refocused its advertising campaign to match the lifestyle message on its Web site. There is now advertising of Viagra at NASCAR races, and Pfizer hired 39-year-old Rafael Palmeiro, a former Texas Ranger baseball player as a spokesman ( Figure 1 ) [ 7].

Pfizer teamed up with Sports Illustrated magazine to create the Sportsman of the Year Trivia Game ( http://www.viagra.com/sports/index.asp).

Between 1999 and 2001, Pfizer spent over US$303 million in direct-to-consumer advertising to get its message about Viagra to men [ 8–10].

Besides the large promotion budget, Pfizer has also paid a number of doctors to act as “consultants,” delivering public lectures and appearing in the mass media to expound on ED and Viagra [ 11] Pfizer denies that it is targeting younger men or that it is positioning Viagra as a lifestyle drug. Mariann Caprino, a spokeswoman for the company, is quoted in the New York Times as saying, “Have we gone out and given our advertising agency instructions to speak to this young population? But the message from the pictures on the Web site, in magazine ads, and from people like Rafael Palmiero is that everyone, whatever their age, at one time or another, can use a little enhancement; and any deviation from perfect erectile function means a diagnosis of ED and treatment with Viagra. Increasingly, the age profile of men using Viagra reflects the younger audience that Pfizer denies it is targeting.

Between 1998 and 2002 the group showing sildenafil 20 mg walgreens the largest increase in Viagra use was men between the ages of 18 and 45, and only one-third of these men had a possible etiologic reason for needing Viagra [ 12]. Economic and Social Implications of the Expanding Market for Lifestyle Drugs. Drug companies have identified lifestyle drugs as a “growth market.” The problems that they are designed to treat are easily self-diagnosed—we can all see if we are bald or fat—and as the baby boomers age, the population looking to these drugs will continue to grow.

Drug companies, driven by profit, go where the money is. Because of the potential size of the market for Viagra, paying for it in unlimited quantities will be very expensive. If we believe the prophets of technology, soon there will be drugs for memory enhancement and the possibility of genetic manipulation to make us taller or to keep a full head of hair. Do we accept our limitations with grace, or is it legitimate to seek technological solutions for them?

In one corner is the view of health as freedom from disease, where “the central purpose of health care is to maintain, restore, or compensate for the restricted opportunity and loss of function caused by disease and disability” [ 13].

In this model, a just medical system would not cover treatments and interventions that aim to enhance abilities not affected by disease and disability.

Opposing this is an expansionist definition, such as the one offered by the World Health Organization, where health is “a state of complete physical, mental and social well-being” ( http://www.who.int/about/definition/en/print.html). If we accept this view, then are we not obliged to provide for people who want to enhance themselves so that they can achieve mental and social well-being?

This debate is further complicated because there is not an equal balance in how we look at the options of accepting limitations and seeking enhancement. In a market-driven world, the money is in promoting enhancements, not in accepting limitations.

The ad featuring the man who chooses not to accept even occasional erection problems is one example of how commercial pressures bias the debate [ 14]. Because of the possibility that large numbers of men would request Viagra from their doctors, getting insurance companies to pay for Viagra presented Pfizer with special problems.

Early on, Kaiser Permanente refused to cover Viagra for its 9 million members because of sildenafil tablet online shopping costs expected to be in the range of US$100 million per year [ 11].

According to one interpretation, reactions from insurers such as Kaiser Permanente were the reason that Pfizer put in place a US$35 million campaign to change insurers' decisions [ 11].

Another goal of Pfizer's campaign was to make ED an acceptable topic for public discourse, in order to remove the stigma attached to it and increase the possibility that third parties would provide coverage. Viagra presents a microcosm of the debate surrounding drugs that enhance lifestyle choices.

The drug is effective and safe for people with medical problems warranting treatment, but it also can be used by a much wider population.

The company that manufactures the drug, recognizing that the potential market is huge, has aggressively targeted that much larger community.

Pfizer's well-financed campaign was aimed at raising awareness of the problem of ED, while at the same time narrowing the treatment possibilities to just a single option: medication.

Having succeeded in turning Viagra into a consumer product, Pfizer then turned its attention to payers in order to reap the benefits of the expanded market.

Ultimately, there must be a debate about how limited resources for health care should be spent and who should make those decisions. Are men who seek to enhance their normal sexual function “worthy” enough to have their treatment paid for?

If we pay for drugs and other procedures that enhance lifestyles, then other treatments either may not get funded at all or may become inadequately funded. As the number of enhancement treatments grows, the scenario surrounding Viagra will become all too familiar with other drugs.

Now is the time to start preparing for how we will deal with the inevitable explosion of drugs and other interventions that can make us “better than well” [ 16].

Erectile dysfunction (ED) is one of the most common conditions affecting middle-aged and older men.

Nearly every primary care physician, internist and geriatrician will be called upon to manage this condition or to make referrals to urologists, endocrinologists and cardiologists who will assist in the treatment of ED.

This article will briefly discuss the diagnosis and management of ED.

In addition, emerging concepts in ED management will be discussed, such as the use of testosterone to treat ED, the role of the endothelium in men with ED and treating the partner of the man with ED.

Finally, future potential therapies for ED will be discussed. erectile dysfunction endothelial dysfunction testosterone testosterone deficiency androgen deficiency testosterone replacement cardiovascular disease stem cells gene therapy.

erectile dysfunction endothelial dysfunction testosterone testosterone deficiency androgen deficiency testosterone replacement cardiovascular disease stem cells gene therapy. Nearly every primary care physician, internist and geriatrician now understand that many older men retain an interest in sexual activity as they age.

Some primary care physicians think that sexual potency in older men is the norm, and that if it is lacking, it is ‘all in the head.’ This viewpoint has not been supported by current literature. The Massachusetts Male Aging Study (MMAS) found that 52% of men between 40 and 70 years old reported having some form of erectile dysfunction (ED).1 The reality is that ED is a natural part of ageing and that the prevalence increases with age. In the MMAS, they found that roughly 50% of men at 50 years old, 60% of men at 60 years old and 70% of men at 70 years old had ED.

Thus, nearly all men who live long enough should develop ED.

The myths that surround the problems of impotence or ED confound the attempts of patients to receive treatment and the attempts of physicians to help them.1. 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. The percentage of men who engage in some form of sexual activity decreases from 73% for men aged 57–64 years to 26% for men aged 75–85 years.3 For some men, this constitutes a problem, but for others it does not.

The aetiology for this decline in sexual activity is multifactorial and is in part due to the fact that most of the female partners undergo menopause at 52 years of age with a significant decline in their libido and desire to engage in sexual activity. A study by Lindau and colleagues3 that examined sexuality in older Americans showed that 50% of the men in a probability sample of more than 3000 US adults reported at least one bothersome sexual problem and 33% had at least two such problems.3 This article will review the normal changes that occur with ageing, factors that influence these changes, individual variations and perspectives, and the available treatment options for ED and androgen deficiency.

Impotence treatments were discussed in the oldest Chinese text, The Yellow Emperor’s Classic of Internal Medicine, which describes traditional Chinese medicine during the time of the Yellow Emperor’s rule which ended around 2600 BC.

One of the treatments for impotence discussed is a potion with 22 ingredients.4. Nearly 1000 years later, the Egyptian Papyrus Ebers, a medical Egyptian document dated 1600 BC, describes a cure for impotence in which baby crocodile hearts were mixed with wood oil and applied topically to the penis.4.

In 1973, Dr Brantley Scott from Baylor College of Medicine reported on the implantable inflatable prosthesis that urologists still use today.5.

The major breakthrough occurred in 1998 when sildenafil became the first oral drug to be approved to treat ED.4 This was followed by the use of tadalafil and vardenafil as similar phosphodiesterase-5 inhibitor oral medications for treating ED in 2003.4.

Overview of physiological changes and other risk factors.

As with most other organ system in the human body, changes and loss of function is normal consequence of the ageing process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle.

Accompanying the decrease in testosterone is a decrease in erections which also has a component in decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life threatening, they can impact a man’s relationship with his partner, and also ED may be a harbinger of other undiagnosed conditions such as coronary artery disease (CAD), hypercholesterolaemia or diabetes mellitus.6. ED is defined as the inability to achieve a full erection or the inability to maintain an erection adequate for sexual intimacy.

Other types of sexual dysfunction such as premature ejaculation and low libido may occur; however, the most common and disruptive problem in men is ED.

Although most men will experience periodic episodes of ED, these episodes tend to become more frequent with advancing age.

Medical conditions, such as hypertension, diabetes mellitus, and cardiovascular disease (CVD), and psychological conditions, such as depression and anxiety, also contribute to sexual dysfunction in middle-aged or elderly men.

CVD and hypertension cause a narrowing and hardening of the arteries, leading to reduced blood flow to the corporal bodies, which is essential for achieving an erection. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis.

Men with diabetes are four times more likely to experience ED, and on average, experience ED 15 years earlier than men without diabetes.7 Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED.8. 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. Men being treated for prostate cancer with treatments such as radical prostatectomy, radiation therapy or the use of Lutenizing hormone-releasing hormone (LHRH) agonists and antagonists can expect that ED may accompany these treatments.12.

Smoking, excessive use of alcohol and illicit drugs are also associated with ED.13 A study in 2005 suggests that ED is not only more likely among men who smoked compared with those who never did, but that in younger men with ED, cigarette smoking is very likely the cause of their impotence.14 15.

Also, it is important to remember that there are psychogenic issues such as performance-related issues, traumatic past experiences, relationship problems, anxiety, depression and stress that can certainly cause or be considered a comorbid condition contributing to ED.

Bullet point: Ageing and comorbidities as well as polypharmacy factor greatly influence the development of ED. The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present.

The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16. 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.

It is important to understand that ED is frequently, if not usually, directly related to endothelial dysfunction, and that the release of NO by the vasculature of the penile arteries is directly related to the function of intact, healthy endothelium.

In

the

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. Download figure Open in new tab Download powerpoint. Link between oxidative stress, endothelial dysfunction and ED.

CVD, cardiovascular disease; ED, erectile dysfunction. 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.

Since endothelial dysfunction, CVD and ED are closely associated in epidemiological studies, the question for clinicians is whether to recommend the man presenting with ED undergo a cardiovascular (CV) evaluation.

Clearly, based on numerous studies, ED can be considered at least a ‘marker’ for possible further vascular disease or CVD.15 In their report, Vlachopoulos and coworkers make the point that the man presenting with ED, the clinician, is offered an opportunity to attempt to improve the health of the man by addressing lifestyle modification, and consider further vascular evaluation owing to the clear relationship between endothelial dysfunction, ED and CVD.19.