Definition and classification of premature ejaculation

The term “premature ejaculation” throughout the twentieth century and still refers to the subject of discussion in modern andrology and sexopathology.

The International Society for Sexual Medicine (ISSM) defines this copulatory disorder: “Premature ejaculation is a male sexual dysfunction that is characterized by:

  • always or almost always by ejaculation before penetration of the penis or during the first minute from the beginning of sexual intercourse during the first sexual experience (primary form) or a significant decrease in the time of intravaginal delay of ejaculation to 3 minutes or less (acquired form);
  • the lack of the ability to delay ejaculation during sexual intercourse always or almost always;
  • the presence of a negative impact on the interpersonal relationships of partners in the form of anxiety, frustration and avoidance of coitus.

It is noteworthy that this definition applies only to vaginal sexual contact in heterosexual partners.

According to ICD-10, premature ejaculation (code F52. 2) is the inability to control ejaculation to the extent that is sufficient for both partners to receive satisfaction from sexual intercourse. This definition is more based on a subjective assessment of the quality of coitus within a couple.

Additionally, the following forms of early ejaculation are distinguished – variable and subjective. Persons with a variable form only sometimes note problems with ejaculation, but this fact should be perceived as a natural feature of a man’s sexuality. In the subjective form, as a rule, complaints about early ejaculation are noted, while the value of VISAS remains within the normal range. It should be understood that the development of this form is based on the psychological and cultural characteristics of the individual.

Premature ejaculation: Epidemiology

Information about the prevalence of premature ejaculation (PE) in the population is the cause of a lot of controversy in the urological community. The lack of a single definition, classification, and optimal criteria for sampling patients with PE led to significant variability in statistical data.

E. Serefoglu et al. the prevalence of 4 forms of PE was studied in 1296 male patients (average age 41.9±12.7 years). The frequency of occurrence of PE was 20%. Separately, for the primary, secondary, variable and subjective forms, this indicator was 2.3, 3.9, 8.5 and 5.1%, respectively.

In the study of J. Gao et al. 3016 men took part and this indicator was higher than in a similar study by E. Serefoglu et al., and amounted to 12.3; 18.7; 44.9; 24.8%. It was noted that men with a secondary form of PE most often belonged to the older age group, had a large body mass index, somatic diseases, and also suffered from nicotine addiction. The frequency of occurrence of PE in them exceeded 25.8%.

The prevalence of primary and secondary forms of early PE in the general population is 5%. This indicator is consistent with previously published epidemiological data, which states that about 5% of men have a VIZ of less than 2 minutes.

Treatment of premature ejaculation

Psychotherapy/behavioral therapy
The main tasks of psychotherapy for men with PE are: 1) development of skills that allow for further ejaculatory control; 2) elimination of interpersonal problems of partners. Treatment can be carried out both individually and in a group.

The most well-known and used methods of behavioral therapy include “compression technique” and “stop-start technique”.

In the first case, the partner performs a sufficiently strong compression of the glandular part of the penis at the moment immediately preceding ejaculation (the woman puts her thumb on the bridle of the penis, and the index and middle fingers-on the coronal furrow and under it, on the opposite side of the penis). For 4 seconds. the partner squeezes the penis hard, and then abruptly releases it.

With the “start-stop” technique, the prolongation in time of the moment of ejaculation is achieved by stopping frictions at the first urge to ejaculate. After a pause, it is possible to continue coitus until the next sensations of the upcoming ejaculation appear.

To date, there are 3 publications that allow you to objectively evaluate the results of this type of treatment. In the work on the topic psychotherapy/behavioral therapy of PES. Althof et al. we came to the conclusion that the effects of behavioral therapy in patients with accelerated ejaculation are inconclusive and contradictory. A similar conclusion was reached in their work by S. Fruhauf et al.

premature ejaculation

For people with a variable form of PE, just a consultation with a urologist is enough. The doctor needs to explain to the patient that his case does not relate to pathology. After an unsuccessful attempt to convince a patient with a subjective form of PE to the contrary, it should be recommended to seek help from a psychotherapist.

Unfortunately, there is little data in the modern literature that can be used to judge the above methods of treatment, and the available publications do not meet the requirements for the design of studies (a small sample of patients, differences in the definitions of PE).

Pharmacotherapy

Modern pharmacotherapy has wide opportunities for the correction of PE. It includes the use of such groups of drugs as local anesthetics, SSRIs, phosphodiesterase inhibitors of type 5 (for example, Viagra or dopoxetine) and a-blockers.

Local anesthetics

Since an increase in the sensitivity of the glandular part of the penis plays a key role in the development of the primary form of PE, the use of local anesthetics is proposed to reduce sensory perception.

External use of gel, cream, spray based on lidocaine, prilocaine and benzocaine is the most long-standing method of drug treatment. When using them, it is worth remembering that they can cause local side effects in the form of a decrease in penile sensitivity, ED and allergic reactions on the skin.

Sildenafil – The mechanism of action

The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow. Sildenafil does not have a direct relaxing effect on the isolated human cavernous body, but it enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the breakdown of cGMP.

Sildenafil is selective against PDE-5 in vitro, its activity against PDE-5 exceeds the activity against other known PDE isoenzymes: PDE-6 — by 10 times; PDE-1-by more than 80 times; PDE-2, PDE-4, PDE-7–PDE-11 — by more than 700 times. Sildenafil is 4000 times more selective against PDE-5 compared to PDE-3, which is of crucial importance, since PDE-3 is one of the key enzymes for the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Sildenafil restores impaired erectile function under conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Sildenafil: clinical data

Cardiological studies. The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and diastolic pressure-5.3 mm Hg. A more pronounced, but also transient effect on blood pressure was observed in patients taking nitrates.

In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic pressure at rest decreased by 7 and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not disrupt blood flow in stenosed coronary arteries, and also led to an increase (by about 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries. In a double-blind placebo-controlled study, 144 patients with erectile dysfunction and stable angina, taking antianginal drugs (except nitrates), performed physical exercises until the severity of angina symptoms increased. The duration of the exercise was significantly longer (19.9 seconds; 0.9-38.9 seconds) in patients taking sildenafil in a single dose of 100 mg, compared with patients receiving placebo.

In a randomized, double-blind, placebo-controlled study, the effect of changing the dose of sildenafil (up to 100 mg) was studied in men (n=568) with erectile dysfunction and arterial hypertension taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in those taking more than three antihypertensive drugs.

Studies of visual disorders. In some patients, 1 hour after taking sildenafil at a dose of 100 mg, a slight and transient impairment of the ability to distinguish shades of color (blue/green) was detected using the Farnsworth-Mansell 100 test. After 2 hours after taking the drug, these changes were absent. It is believed that the violation of color vision is caused by the inhibition of PDE-6, which is involved in the process of color transmission in the retina of the eye. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

In a placebo-controlled cross-sectional study of patients with proven early-age macular degeneration (n=9), sildenafil in a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision assessed by special visual tests (visual acuity, Amsler grid, color perception, color passage modeling, Humphrey perimeter and photostress).

Effectiveness. The efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The effectiveness of the drug was evaluated globally using an erection diary, the international index of erectile function (a validated questionnaire on the state of sexual function) and a partner survey.

The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies conducted and confirmed in long-term studies lasting 1 year. In fixed-dose studies, the ratio of patients who reported that the therapy improved their erection was 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose) and 82% (viagra – sildenafil 100 mg dose) compared to 25% in the placebo group. The analysis of the international index of erectile function showed that in addition to improving the erection, treatment with sildenafil also increased the quality of orgasm, allowed achieving satisfaction from sexual intercourse and general satisfaction.

According to the generalized data, among the patients who reported an improvement in erection during treatment with drugs, there were 59% of diabetic patients, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries (versus 16, 15 and 12% in the placebo group, respectively).

sildenafil

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction. After oral administration, sildenafil is rapidly absorbed. The absolute bioavailability on average is about 40% (from 25 to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses the activity of human PDE-5 by 50%. After a single dose of sildenafil at a dose of 100 mg, the average Cmax of free sildenafil in the blood plasma of men is about 18 ng/ml (38 nM). Cmax when taking sildenafil orally on an empty stomach is achieved on average within 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not significantly change (AUC decreases by 11%).

Distribution. The Vss of sildenafilum is on average 105 liters. The association of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of viagra (an average of 188 ng) was detected in semen 90 minutes after taking the drug.

Metabolism. Sildenafil is metabolized mainly in the liver under the action of the isoenzyme CYP3A4 (main pathway) and the isoenzyme CYP2C9 (minor pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE-5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of tablets. The N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 hours.

Withdrawal. The total clearance of sildenafil is 41 l / h, and the final T1/2 is 3-5 h. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and to a lesser extent by the kidneys (about 13% of the oral dose).

Special patient groups: Old age. In healthy elderly patients (older than 65 years), the clearance of sildenafil is reduced, and the concentration of free sildenafil in blood plasma is about 40% higher than in young patients (18-45 years). Age does not have a clinically significant effect on the frequency of side effects.

Impaired renal function. With mild (creatinine Cl 50-80 ml/min) and moderate (creatinine Cl 30-49 ml/min) degree of renal insufficiency, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal insufficiency (creatinine Cl < 30 ml/min), the clearance of sildenafilum decreases, which leads to an approximately twofold increase in the values of AUC (100%) and Cmax (88%) compared with those of normal renal function in patients of the same age group.

Liver function disorders. In patients with cirrhosis of the liver (classes A and B according to the Child-Pugh classification), the clearance of medication decreases, which leads to an increase in the values of AUC (84%) and Cmax (47%) compared to those with normal liver function in patients of the same age group. The pharmacokinetics of viagra in patients with severe hepatic impairment (Child-Pugh Class C) has not been studied.

Diagnosis of erectile dysfunction today

Diagnosis of erectile dysfunction (ED). ED is a widespread condition that is not life – threatening, but affects the physical and mental health of men. ED has a significant impact on the quality of life of both the man himself and his partner and family members.

According to the World Health Organization (WHO), erectile dysfunction is observed in every tenth man over the age of 21. At the age of 40-50 years, ED is detected in 40% of men, in 50-60 years in 57%. Every third man over the age of 60 is not able to perform sexual intercourse at all.

To date, it is known that an erection is a complex psychoneurovascular reaction that occurs as a result of the close interaction of the endocrine, nervous, and cardiovascular systems. When these systems become discoordinated and men lose the ability to achieve or maintain sufficient erections to satisfy their sexual needs, a condition called ED develops.

ED is a multifactorial, polyethological disease. The occurrence of an adequate erection of the penis can be significantly influenced by three key factors: systemic diseases, poor nutrition and medication. It should be noted that with age, the frequency of somatic burden increases, which negatively affects erectile function, in particular, arterial hypertension, coronary heart disease and diabetes mellitus develop. In this regard, a comprehensive personalized approach to the diagnosis of ED is needed to determine the true cause of the development of ED and determine further treatment tactics.

Today, in addition to lifestyle modification (maintaining sufficient physical activity, quitting smoking) and limiting risk factors (normalizing lipid levels, blood pressure, and blood sugar), there are three lines of ED therapy. The first line includes the use of phosphodiesterase inhibitors of the fifth type, the second – vacuum devices for erection, shock wave therapy, intracavernous injections. Finally, the third-line method is the implantation of penile prostheses (phalloprosthesis). To determine the pathogenetic treatment of ED, its nature should be established. A personalized treatment and diagnostic approach with the use of additional research methods will allow you to get the expected better treatment results in the long term.

Diagnosis of erectile dysfunction

One of the paradigms of modern ED diagnostics currently implies a single algorithm for examining all patients. However, this position leads to ineffective treatment.

It is known that ED is not a disease, but a symptom. For example, to date, there is sufficient evidence that ED can be a potential marker of cardiovascular diseases, since it occurs due to endothelial dysfunction, damage to the coronary arteries and peripheral vessels. Thus, endothelial dysfunction can lead to a violation of the mechanisms of normal blood flow in the pelvis, as well as in the coronary circulation system. At the same time, the pathogenetic causes of endothelial dysfunction may be different.

In this regard, today more than ever, the question of optimizing the existing modern methods of diagnosing ED, aimed at assessing the state of the endothelium, as well as the androgen and psychosexual status of a man, is relevant. The main task of the survey is to form a complete objective picture of the state of health of a man and actively correct the detected deviations. In this case, the treatment of ED will be highly effective, as pathogenetically justified and safe as possible.

Currently, the examination of men suffering from ED includes a number of laboratory and instrumental diagnostic measures. In addition to assessing the history of the disease, sexual disorders, conducting questionnaires (according to the International Index of Erectile Function, the Questionnaire of Age-related symptoms of Androgen Deficiency in men, the Hospital Scale of Anxiety and Depression), laboratory tests (determining the level of glucose, total testosterone, lipid profile, etc.), special research methods deserve special attention. These include assessment of nocturnal penile tumescence and rigidity, pharmacodopplerography of penile vessels, assessment of systemic endothelial function, electrophysiological examination of the penis, and cavernosography.

Assessment of nocturnal penile tumescence and penile rigidity

The greatest difficulties in the study of erectile disorders are caused by the differential diagnosis of psychogenic and organic disorders of erectile function. The preservation of spontaneous erections in the absence of adequate ones is considered an indirect sign of psychogenic disorders. A differential diagnosis between psychogenic and organic forms of ED can be made, including the assessment of nocturnal penile tumescence.

Nocturnal penile tumescence was first described by H. M. Halverson in 1940, who observed infants, and then by P. Ohlmeyer in 1944, who observed healthy men of all ages. In healthy men, during the night in the REM sleep phase, there are three to five episodes of spontaneous erections lasting on average about 10-15 minutes (from 20% of the sleep time during puberty to two to seven minutes in older age).

Monitoring of the development of nocturnal penile tumescence is carried out using the RigiScan computerized system, developed in 1985.The system allows you to qualitatively and quantitatively evaluate nocturnal erections. To date, the study of nocturnal penile tumescence remains an important tool in the diagnosis of ED, since it makes it possible to analyze the effectiveness of adequate therapy aimed at restoring sexual disorders.

Thus, it was shown that the assessment of penile tumescence helps to predict the effect of taking phosphodiesterase inhibitors of the fifth type (viagra, cialis, levitra or their analogues). S. M. Elhanbly demonstrated a positive correlation between rigidity in the head and base of the penis and the effectiveness of sildenafil.

In men who have undergone radical nerve-sparing prostatectomy, the assessment of nocturnal penile tumescence is important for an adequate choice of pharmacotherapy for the purpose of early recovery of sexual function. According to A. Bannowsky, with a well-performed operation, episodes of spontaneous erection are observed as early as the first night after the removal of the urethral catheter. In the absence of nocturnal penile tumescence, it is assumed that the neuronal integrity of the cavernous nerve has been damaged, and then, according to the authors, it is necessary to additionally use intracavernous injections to restore erectile function.

Assessment of nocturnal penile tumescence is also important for young males with spina bifida pathology, since the level of spinal cord damage plays a key role in the rehabilitation of sexual function.

diagnosis of erectile dysfunction

However, in patients with diabetes, the value of this test is reduced, since many of them have concomitant somatic diseases and take medications that affect the reliability of the results.

False-positive results can be observed in neurogenic ED. False negative-in old age of the patient, with his agitation, depressive states, sleep disorders and hypogonadism, as well as taking alcoholic beverages, antiandrogens, antidepressants, barbiturates, benzodiazepines, diuretics, sympatholytics, anticholinergic anticonvulsants, sedatives and narcotic drugs, nicotine.

However, the mechanism of development of spontaneous erections differs from adequate ones, and patients who have excellent nocturnal erections may have signs of ED. In this regard, the normal values according to the results of the study of nocturnal penile tumescence do not exclude organic ED. Therefore, the question of the diagnostic value of this method of investigation remains debatable to this day, and the assessment of nocturnal penile tumescence is mainly used in scientific and clinical studies.

Conclusion

The presented review of works published over the past decade confirms the fact that the main task of diagnosis of erectile dysfunction is to establish its true cause. It is obvious that it is advisable to use research methods with proven effectiveness, since this will ensure an effective approach to treatment. Currently, methods for diagnosis of erectile dysfunction need to be optimized. It is necessary to develop a personalized diagnostic algorithm aimed at assessing the state of the cardiovascular system, endothelium, androgen status, etc. to improve the effectiveness and safety of treatment for men suffering from various forms of ED.