Viagra, Levitra or Cialis – Which works best? 

2.3PREVALENCE OF ERECTILE DYSFUNCTION

The Massachusetts Male Aging Study (Feldman et al.1994) found an ED prevalence of 52 % in 40 – 70-year-old men. Another US study (Laumann et al.1999), the “National Health and Social Life Survey”,noted that 31% of men in the 18 - 60 year age grouphad already experienced ED. In the German“Cologne Male Survey” (Braun et al. 2000), a significant age-correlated increase of 10% in the incidence of ED was found in men between the ages of 40 and 49, 16% in men between 50 and 59, 34% in menbetween 60 and 69, and over 50% in men between 70and 80 years of age. The overall prevalence (age range 30-80 years) was 19.2%. Studies in England and France have yielded similar results (Spector and Boyle 1986, Giuliano et al. 1996). These results mean that almost one in five men experiences erectiles dysfunction.Contrary to the earlier view that the cause of ED is predominantly psychogenic, it is now known to be due mainly to organic dysfunctions, at least in the 50-

plus age group (Kaiser 1999).

2.4CAUSES OF ERECTILE DYSFUNCTION

In most cases, erectile dysfunction is due to several causes. Cardiovascular risk factors are the most important. According to the Cologne study (Braun et al. 2000), 20% of ED patients suffer from diabetes mellitus, 30% from arterial hypertension, 30% are smokers and 38% regularly consume alcohol.

Similar results were also found by Pritzker (Pritzker 1999). According to his studies, 20% of ED

patients show undiagnosed diabetes mellitus, 48% hypertension and 70% raised cholesterol levels.

Similarly, Roumeguère et al. (2001) found diabetes mellitus in 20% of ED patients, hypertension in 26%, and hyperlipidaemia in 76%.

2.5. THERAPEUTIC OPTIONS FOR ERECTILE DYSFUNCTION

The first objective of every doctor is to cure the medical condition. Therefore, the primary goal in ED treatment is to determine the aetiology of the disease and treat it when possible, and not to treat the symptom alone. (Wespes et al. 2002). Nevertheless, it has been shown that treatment of organic risk factors alone often does not significantly improve the patient´s erectile function (Montorsi et al. 2002).

Oral drug treatments, the use of an erection-supporting vacuum pump and/or psychological sex therapy are symptom-orientated treatments available for erectile dysfunction (Montorsi et al. 2002). If none of these brings the desired success, treatment with intracavernosal or intraurethral injections of vasoactive substances can be attempted as second-line treatments (Montorsi et al. 2002). However, most patients find this a very unpleasant experience. Penis implants as mechanical aids play hardly any part in treatment since the introduction of sildenafil. There are various approaches in drug treatment, which differ significantly in terms of their clinical efficacy. For local use with intraurethral or intracavernosal injection (corpus cavernosum auto-injection therapy), the synthetic prostaglandin analogue (PGE1) alprostatil, for example, can be used. This treatment produces an erection by increasing the cAMP level in the corpus cavernosum (Andersson 2001).

In terms of oral therapeutic options, a fundamental distinction is made between a central and a peripheral action site.The centrally acting substances available are the dopamine receptor agonist apomorphine and the selective alpha2 adrenoceptor blocker yohimbine.

436 EUROPEAN JOURNAL OF MEDICAL RESEARCH October 29, 2002

Yohimbine acts both centrally as a noradrenergic agonist and peripherally as an alpha2 adrenoceptor

blocker (Hatzichristou 2001). It has not yet been possible to demonstrate significant efficacy above the

placebo level in a robust study. Accordingly, yohimbine has been classified as inadequately effective for the treatment of organic ED in the guidelines of the American Urology Association (Montague et al. 1996).

Apomorphine produces its effect by stimulating central dopamine receptors (predominantly D2) in

the paraventricular nucleus of the hypothalamus, which activates pro-erectile pathway systems (including NO and oxytocin) and in this way produces an erection (Hatzichristou 2001). In a double-blind, placebo- controlled study by Dula et al. (2001), an erection firm enough for intercourse was obtained in 46.9 % of ED patients on apomorphine treatment, compared with a baseline figure of 21.9 %. In comparison with the placebo rate of 32.3 %, there is an absolute improvement of 14.6 %, which is not a satisfactory result. This is also evident in the low market share for apomorphine preparations, which in the case of Europe is less than 5 % (IMS data as at April 2002). The most effective form of oral treatment are phosphodiesterase inhibitors, which will therefore be discussed in greater detail.

3. PHOSPHODIESTERASES AND THEIR INHIBITORS

To date, 11 PDE groups (PDE 1-11) are known, and these can be further differentiated into 21 sub-groups and about 53 splice variants. Since these PDE forms are involved in the most diverse bodily functions in the form of in some cases very similar molecules, this raises the question of whether the PDE-5 inhibitors that are relevant to ED treatment also inhibit other phosphodiesterases.

3.1. MECHANISM OF ACTION OF PDE-5 INHIBITORS

Phosphodiesterase inhibitors used for ED treatment are selective, competitive inhibitors of phosphodiesterase type 5 (PDE-5), an enzyme that breaks down cyclic guanosine monophosphate (cGMP) in various tissues, the second messenger of NO (Boolell et al. 1996). The selective and competitive PDE-5 inhibitor is sildenafil. PDE-5 inhibitors potentiate the musclerelaxant effect of NO and are pharmacologically active only where cGMP synthesis is activated (e.g. through NO) (Ballard et al. 1998, Jeremy et al. 1997).

Following sexual stimulation, NO is released in the corpus cavernosum from nerves, vascular endothelium and smooth muscle cells, as a result of which the vessels in the penis and corpus cavernosum dilate, producing an erection (Burnett 1997). By inhibiting cGMP breakdown, PDE-5 inhibitors enhance the vasodilatory effect of NO and restore the ability to achieve an erection in patients with erectile dysfunction.