In the modern sense, erectile dysfunction (ED) is the inability to achieve and / or maintain an adequate erection of the penis, which restricts or makes it impossible to have satisfactory sexual intercourse.
Epidemiology. ED is an extremely common disorder, occurring in 40% of men aged 40-50, 50% of men aged 50-60, and 70% of men over 60, regardless of country or ethnicity (Massachusetts study of older men, MMAS). Erectile dysfunction is especially common in highly developed countries. For example, in the US, ed affects from 10 to 30 million men, in Germany – from 3 to 4 million.
Etiology of ED. There are psychogenic, organic and mixed ED. Previously, the main cause of ED was considered to be various psychological problems, but now it is believed that ed in 80% of cases has an organic nature and occurs as a complication of various somatic diseases. The main causes of ED are presented in table 1.
Modern research that has clarified the true causes and mechanisms of erections has shown that ED in about 80% of cases is the result of various somatic diseases. At the same time, almost all epidemiological studies on ED revealed a link between ITS occurrence and arterial hypertension (AH), diabetes mellitus, coronary heart disease and atherosclerosis. Moreover, according to some authors, the detection of ED may indicate that the patient has one of these diseases in a hidden form. The frequency of ED in the presence of a history of the following diseases are shown in table. 2.
Due to atherosclerotic vascular lesions of the penis occurs not only mechanical disruption of blood flow, but also disrupted production of neurotransmitters, reduced elasticity of blood vessels.
Hypertension can cause ED regardless of whether a person suffers from atherosclerosis or not. If you do not treat hypertension for a long time, the walls of blood vessels, constantly exposed to high blood pressure, become dense and inelastic and the vessels are not able to supply the organs with the necessary amount of blood. In diabetes mellitus, ED develops three times more often and 10 to 15 years earlier than in a healthy population, it occurs, according to A. Guay et al. (1998) in 50-75% of diabetic men.
According to A. Guay (2002), the main causes of organic ED in DM are diabetic polyneuropathy, macro – and microangiopathy.
The development of ED is OFTEN associated with taking various medications (table 3).
Psychogenic ED. Men with depression have a 25% chance of developing ED in mild depression to almost 90% in severe forms. ED can be triggered by severe stress. More often, however, there is a psychogenic variant associated with a man’s disbelief in his own sexual usefulness (situational ED).
Diagnosis of ED
The examination begins with the collection of anamnesis. First of all, it is necessary to identify predisposing factors (including atherosclerosis with its various manifestations, hypertension, diabetes, dyslipidemia, kidney failure, mental and neurological diseases, Smoking, alcoholism, etc.), which often requires the involvement of a therapist. The collection of information facilitates the use of adapted questionnaires for patients with ED. The International index of Erectile Function (IIEF) is the most widely used index in clinical research).
Physical examination includes General examination (body weight, height, body mass index, BLOOD pressure, etc.), assessment of androgen status (development of external genitalia and secondary sexual characteristics), rectal examination. The pulse of the femoral and peripheral arteries is measured and their auscultation is performed.
Laboratory examination necessarily includes the determination of testosterone and blood glucose levels; according to the indications, the level of blood lipids, prolactin, and PSA is determined.
The next screening study may be the monitoring of nocturnal spontaneous erections using a computer-based monitoring system for the quality and quantity of erections (RigiScan).
In healthy men during the night, during the REM sleep phase, there are 4-6 episodes of erections, lasting 10-15 minutes. Men with ED have a decrease in the quality and number of spontaneous erections during nighttime sleep. The method allows differentiating organic and psychogenic ED and suggests the nature of erectile dysfunction (vasculogenic, neurogenic).
Of great importance is the study of pharmacological artificial erection. The rate of erection development, its degree on the six – point Unema scale (1987), duration, and the nature of changes in ortho-and clinostasis are estimated (table 4).
A positive response to the pharmacological load is considered if a full — fledged erection (Er5) develops within 5-10 minutes, lasting 30-60 minutes. Delayed development of an erection (20-25 min) may indicate arterial insufficiency of the penis. Rapid detumescence indicates venous leakage. The absence of tumescence or the development of incomplete tumescence after pharmacological loading may indicate sclerosis of the cavernous tissue or decompensated arterial or venous insufficiency. For Er4-Er5 results, no Doppler study is performed. With the results of Er0—Egz, dopplerography of the penile vessels is shown.
Doppler ultrasound (uzdg) penile vascular system is indispensable in the diagnosis of vasculogenic erectile dysfunction. In the energy Doppler mode, microcirculation can be better evaluated, and B-mode is necessary for detecting structural changes in cavernous fibrosis and Peyronie’s disease, but the results of the study using the duplex method are much more complete than when using the B and d modes separately. ultrasound of the penile vessels is more informative if it is performed at rest and with a pharmacologically induced erection.
Treatment of erectile dysfunction
First of all, after assessing the somatic status, the therapist treats the main disease — arterial hypertension, diabetes, etc. Also, drugs that worsen sexual function are canceled.
Treatment of ED includes non-invasive (drug therapy, use of vacuum constrictor devices) and invasive methods (intracavernous injections of vasoactive substances, surgical treatment.
Medications intended for ED CORRECTION are divided into two groups: Central and peripheral action. Central-acting drugs include the dopaminergic receptor agonist apomorphine, testosterone, and the selective A2-adrenergic blocker yohimbine. Peripheral drugs include prostaglandin EJ, phentolamine, and phosphodiesterase type 5 inhibitors.
Until recently, yohimbine was the main method of drug therapy, but its effectiveness does not exceed 10%. Currently, the drug is used mainly for psychogenic ED.
The effect of apomorphine is due to the stimulation of Central dopaminergic receptors (mainly D2 and, to a lesser extent, D1) in the paraventricular nuclei of the hypothalamus and the brain stem.
The most recommended treatment for both psychogenic and organic ED is the use of phosphodiesterase type 5 (PDE5) inhibitors. During sexual stimulation, cyclic guanosine monophosphate (cGMP) accumulates in vascular smooth muscle cells due to activation of the nervous system and the release of nitric oxide (NO). As described earlier, it is cGMP that triggers a cascade of biochemical reactions that lead to the emergence and maintenance of an erection. Normally, its concentration decreases when sexual stimulation ceases due to the destruction of PDE5. In ED, there is a deficiency of cGMP due to various pathogenetic factors, and its destruction by PDE5 leads to insufficient or no erection. PDE5 inhibitors do not have a direct relaxing effect on the cavernous bodies, but they enhance the relaxing effect of nitric oxide by inhibiting PDE5 and increasing the concentration of cGMP during sexual arousal.
A contraindication to the use of PDE5 inhibitors is simultaneous administration of nitrates. With caution, drugs of this group are used in the presence of anatomical deformities of the penis, diseases that contribute to the occurrence of priapism (for example, sickle cell anemia, leukemia) or accompanied by increased bleeding.
The introduction of the first drug from the group of PDE5 inhibitors sildenafil citrate marked a new era in the treatment of ED.
Recently, another drug from this group has become available for clinical practice in Russia — tadalafil, which differs from sildenafil in its chemical structure, selectivity, pharmacokinetic profile and, accordingly, in its clinical effect: the clinical effect of tadalafil develops in a third of patients after 16 minutes and in the vast majority of patients (79%) persists for 36 hours after taking the drug. The long-term effect of the drug allows the couple to choose the time of intimacy more freely. Simultaneous intake of fatty foods and alcohol does not affect the concentration of tadalafil in the blood serum.
Vardenafil hydrochloride — a new powerful selective PDE5 inhibitor
Vardenafil is available in dosages of 2.5; 5; 10 and 20 mg. The drug in the recommended dose of 10 mg should be taken 15-25 minutes before sexual intercourse. If necessary, the dose is increased to 20 mg. In patients taking other medications (for example, alphaadrenoblockers), or in conditions accompanied by reduced metabolism of vardenafil (for example, in elderly patients), the dose should be 5 mg. Do not take the drug more than once a day.
You should also avoid taking the drug in combination with nitrates or alpha-adrenergic blockers (drugs for the treatment of benign prostatic hyperplasia and/or lowering blood pressure), since combined use with these drugs can lead to a sharp decrease in blood pressure and collapse. The drug is not used in patients with an extended Q—T interval due to the possibility of heart rhythm disorders.
Some medications may affect the metabolism of vardenafil, so patients should consult a doctor if they are prescribed a new drug. For example, for patients taking erythromycin, the maximum allowable dose of vardenafil is 5 mg, and for patients taking ritonavir — 2.5 mg once for 72 hours.
The drug is also contraindicated in persons who have suffered a myocardial infarction within the last 6 months, with a constitutionally low blood pressure (systolic BLOOD pressure of 90 mm Hg or lower), uncontrolled increase in blood pressure, unstable angina, severe liver failure, end-stage renal failure requiring dialysis, and retinopathy of pigmentation.
According to research conducted in the Department of urology at the University of Cologne medical center, vardenafil* is more than 10 times more effective than sildenafil and 13 times more effective than tadalafil in blocking the action of the enzyme PDE5. At the same time, vardenafil begins to act record – breaking quickly-within 15 minutes after taking it. The duration of the drug is 4-5 hours (according to the latest data — 8-12 hours). Studies have shown that vardenafil helps in more than 50% of cases when sildenafil is ineffective.
77% of patients after the first intake of vardenafil* (10 mg) report the occurrence of an erection sufficient for successful sexual intercourse. In clinical trials, vardenafil was also found to be effective in 72% of diabetic patients and 70% of patients who underwent prostate surgery.
Since Virag (1982) first proposed intracavernous papaverine injections (ICI) for the treatment of impotence, phentolamine, prostaglandin E1, and several others have been used for this purpose. Currently, prostaglandin E1 is the most popular. Drug doses vary from 5 to 60 micrograms (the average dose is 20 micrograms). The main side effect is pain during the injection. The effectiveness of the PGE-1 intracavernous injection method is 70-80%. This method expands the possibilities of restoring sexual function, allowing you to avoid surgical methods. Also, the method of intracavernous self-injection is indicated for patients who constantly take nitrates.
To avoid the need for self-injection, the PgE1 MUSE (Medicated Urethral System for Erection) transurethral delivery system was developed. Despite the greater ease of use, the system has its drawbacks – pain in the penis, testicles or inguinal region, in about a third of patients, a decrease in blood pressure up to fainting, the irritating effect of the drug on the urethra mucosa, the need to introduce large doses of the drug (125-1000 mcg), which makes therapy very expensive. In addition, 10% of partners after sexual intercourse had a burning sensation in the vagina and the phenomenon of vaginitis. The effectiveness of intraurethral therapy is lower than intra-cavernous and is about 66%. Currently, the percentage of use of this method is no more than 5%.
The mechanism of action of vacuum devices (VP) is simple: with the help of a special device, a vacuum of atmospheric air is created around the penis, which increases the flow of blood to the cavernous bodies and an erection occurs. To maintain an adequate erection, a compression ring is placed on the root of the erect penis, which reduces the outflow of blood from the cavernous bodies. The penis remains erect, which makes it possible to perform sexual intercourse for up to 30 minutes. Clinical effectiveness is complemented by low cost and safety of the procedure. The success of vacuum therapy is achieved in 53-85% of patients, and the frequency of complications (subcutaneous hemorrhage, pain syndrome, etc.) does not exceed 5%.
Surgical treatment methods for ED include surgical treatment of venous insufficiency (efficiency 50-60%), arterial insufficiency (efficacy 20-80%); implantation of penile prosthesis (efficacy 90%). If the patient wishes to use invasive techniques, he has to choose the most appropriate method for the treatment of ED. The doctor’s task is to control and guide the patient’s choice of pathogenetically sound treatment methods.
Thus, timely correction of the therapeutic disease, modern methods of ED treatment – drug therapy, vacuum devices, surgical treatment — in most cases allow to achieve sexual rehabilitation of patients.
Drug therapy with PDE 5 inhibitors is a simple, effective and fairly safe way to treat ED, which is available not only to urologists and andrologists, but also if there is a certain training for General practitioners. The advantages of vardenafil include high efficiency in patients suffering from erectile dysfunction on the background of diabetes mellitus, as well as good tolerability of the drug (no serious side effects in patients with arterial hypertension and tension angina), the possibility of combining with antihypertensive and antianginal agents (with the exception of nitrates).
autor: D.Y. Pushkar – Department of urology, Moscow state medical University