1998 was the year of birth of the world market of drugs for the treatment of erectile dysfunction. In that year, Pfizer introduced to the market Viagra (sildenafil INN), the first of the group of phosphodiesterase type 5 inhibitors. Five years later, two other drugs from this group were commercially available: Cialis (INN tadalafil, Eli Lilly/ICOS) and Levitra (INN vardenafil, Bayer/GlaxoSmithKline). According to IMS Health, already by 2005 the total sales of prescription drugs for the treatment of erectile dysfunction in 7 major pharmaceutical markets in the world (USA, France, Germany, Italy, Spain, UK and Japan) amounted to 1.95 billion dollars, while the growth from the previous year did not exceed 3.5%.
Two centuries ago, little was known about erectile dysfunction - few men then lived to the age when it became a serious problem. According to OECD researchers, in the 1800s, the average life expectancy for men was 31 years. As medical science has progressed, human life has lengthened considerably, but at the same time there has also been a significant increase in the number of sexual disorders that characterize older and older people. Moreover, the changing lifestyle that was accompanied by stress, lack of sleep and irrational nutrition led to the "rejuvenation" of the disease, which increasingly began to affect young people. In many countries, the problem has become a global one, requiring a solution from scientists and practitioners.
Erectile Dysfunction (ED) is defined as "the inability to achieve and/or maintain an erection sufficient to satisfy sexual activity" (Impotence. NIH Consensus Development Panel on Impotence, 1993) when the disorder has been present for at least three months. The term itself was proposed by the U.S. National Institutes of Health to replace the old "impotence," which carried negative connotations and caused disbelief in the prospect of treatment.
According to modern concepts, ED is considered as a marker of other diseases and, therefore, is a major public health problem. WHO experts agree with this statement, stressing that, for this reason, ED deserves attention and high-quality diagnosis with subsequent professional treatment
Today, ED is a widespread condition that reduces the quality of life of millions of men and families. According to various estimates, 30 million men in the United States and 90 to 150 million men worldwide suffer from ED of varying severity.
According to the World Health Organization (WHO), erectile dysfunction occurs in one in ten men over the age of 21. At the age of 40-50 years, ED is already detected in 40% of men, at the age of 50-60 years - in 48-57% of examined men. Every third man over the age of 60 is unable to have intercourse at all.
The observed increase in the incidence of ED, along with the high prevalence of cardiovascular disease, social and psychological discomfort, constitutes a "mutually reinforcing triad", recognized as the main health problem of men in the XXI century. According to specialist forecasts, the number of men with ED may reach 320 mln by 2025, and this trend is likely to be widespread in all countries. Such growth is explained by the increase in the average age of the world population. Although the aging process itself does not lead to ED, related pathologies may contribute to its development.
It should be noted that these figures are approximate, because it is difficult to obtain reliable data on the real prevalence of ED. Despite the magnitude of the problem, not enough attention has been paid to it so far. Often the diagnosis is revealed accidentally, when a patient comes to a urologist with other complaints. The situation is complicated by men's reluctance to talk about such a delicate topic.
Surveys of patients who do not go to a doctor show that the most frequent reason for refusing to see a urologist is a feeling of embarrassment (74%). A significant group (12%) of patients considers erectile dysfunction a "natural age phenomenon," 9% of patients do not consider this disease to be the responsibility of urologists, and 5% of patients are indifferent to sexual function
Therefore, it is possible that ED has significantly broader coverage in the male population. In particular, this is confirmed in a recent study led by Professor Dmitri Pushkar (2013) on the prevalence of ED among men. The results of an anonymous questionnaire survey of 1,225 men between the ages of 20 and 75 showed that 89.9% of respondents experienced erectile dysfunction to some degree. Moreover, 49.7% of men were between the ages of 20 and 45, 32% between the ages of 45 and 59, and 18.3% between the ages of 60 and 75. However, despite the high incidence of this disorder, most of the respondents (71.3%) had mild ED, 6.6% had moderate ED, and severe ED was detected in 12% of the respondents.
The diagnosis of ED includes a number of activities. Firstly, the fact of ED is established. For this purpose, usually different questionnaires are used (International Index of Erectile Function - IIEF, Male Sexual Formula - MSF), examination and palpation of external genitalia, as well as rigidometry are performed. The next step is to find out the causes of ED, which is performed using the following methods: color ultrasonic Doppler sonography, examination of hormonal status, psychological examination, laboratory tests, neurophysiological examination, cavernosography, penile ultrasound, electromyography of pelvic floor muscles. Thorough anamnesis collection is the key to correct diagnosis and further choice of adequate therapeutic tactics
Treatment of patients with ED can be carried out using: oral medications (phosphodiesterase inhibitors (PDE type 5), hormonal therapy, drugs based on herbal substances, etc.); intracavernous injections; vacuum-constrictive devices; prosthetic penis; psychosexual influence, etc.
Because of the polyetiology of ED, there is no universal treatment for this disorder. Lifestyle changes, including smoking cessation, body weight correction, elimination of physical inactivity, and elimination of other risk factors, are of paramount importance. However, lifestyle measures are often not enough. Such patients require the prescription of appropriate treatment methods
Today, type 5 FDE inhibitors, in particular sildenafil, are considered as first-line therapy for ED. The history of development of FDE inhibitors began in the 60s of the last century with studies on the effect of caffeine. It was found that caffeine, being an adenylate cyclase stimulator and affecting cyclic adenosine monophosphate (cAMP) accumulation, can inhibit FDE activity in the liver. Since then, many FDE inhibitors have been synthesized and, subsequently, the existence of several types of this enzyme has been proven, about
with multidirectional effects . Sildenafil was the first FDE type 5 inhibitor to be developed and approved for use. It was originally thought that inhibitors of this enzyme isoform could have a positive effect in coronary heart disease by causing vasodilation of vascular smooth muscle. However, sildenafil proved ineffective in the treatment of heart disease, and the suddenly identified side effect later became the main indication for its use. The action of the drug is physiological. It provides increase of cGMP concentration in smooth muscle cells of penile cavernous body that leads to increase of nitric oxide (NO) level in these cells and, as a result, to their relaxation. Status of the officially registered sildenafil received in 1998 and since then has literally turned the ideas about the approaches to treatment of ED. Today this representative of the group of inhibitors
FDE type 5 is the drug of choice for the treatment of most men with ED. In all the years of sildenafil use in clinical practice, more than 40 million men have received it as conservative therapy for ED