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Erectile dysfunction (ED) means the inability to attain or maintain a penile erection sufficient for intercourse, that is observed for three or even more months. In multicenter studies, it’s been determined that the incidence of ED, especially in elderly men, is associated with many risk factors, often related: age, diabetes mellitus, atherosclerosis, hypertension, obesity, smoking, alcohol abuse, lifestyle sedentary, depression and relatively low incidence education. In line with the outcomes of the long-term Massachusetts Male Aging Study (MMAS), diabetes mellitus is a major risk factor for ED: 35-75% of men with diabetes are diagnosed with ED. ED may also be an early sign of atherosclerosis and cardiovascular system disease.

Microangiopathies lead to dysregulation of the nitric oxide (NO) system. Formed in nerve endings and endothelial cells during sexual arousal, NO activates the guanylate cyclase system, leading to an increase in the concentration of cyclic guanosine monophosphate (cGMP). cGMP activates a particular protein kinase, consuming that your calcium concentration in the cell decreases and the smooth muscle cells of the arteries relax, which leads to an increase in blood flow to the cavernous bodies and the occurrence of a ‘erection.

In the cavernous tissue, beneath the action of a particular phosphodiesterase type 5 (PDE-5), cGMP is converted into the inactive 5′-guanosine monophosphate. With insufficient production of NO by ischemic or damaged endothelium, the concentration of cGMP in vascular smooth muscle cells decreases, as a result of which there is absolutely no increase in blood circulation to the corpora cavernosa and effective erection does not occur. However, the tissue concentration of cGMP is regulated by both the rate of synthesis and the rate of its destruction by PDE-5. Inhibition of cGMP degradation by phosphodiesterase type 5 inhibitors leads to an increase in its concentration in smooth muscle cells, which promotes erection.

Treatment of erection dysfunction
Most doctors start ED treatment with PDE5. Three PDE type 5 inhibitors have already been approved for medical used in Russia: sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), the pharmacokinetics of which differ significantly. The half-life for sildenafil and vardenafil is 4 hours, for tadalafil – 17.5 hours. The equilibrium concentration of tadalafil is reached on the 5th day with daily intake and exceeds the initial 1.6 times, so the drug doesn’t have the opportunity to accumulate, which allows one to use it constantly.

Recently, a variety of studies have been completed showing that the constant usage of tadalafil not only plays a part in the maintenance of erectile function, but could also be used to treat lower urinary tract symptoms (LUTS). Generally in most men over 50 with ED, the most common disease is benign prostatic hyperplasia (BPH), combined with LUTS (frequent urination, dependence on abdominal tenderness when urinating, inability to delay voiding, nocturia , incomplete bladder emptying and low urine flow).

KE Andersson, in an assessment article, discusses the chance of using tadalafil for the treating LUTS occurring in BPH and discusses at length the pathophysiological mechanisms of the development of LUTS. The relationship between your development of LUTS in BPH and ED has been identified in other studies. The outcomes of six completed studies on the use of tadalafil for the treatment of ED and LUTS indicate: tadalafil when taken continuously at doses of 2.5; five; 10 and 20 mg usually do not affect urodynamic parameters: maximum flow rate, detrusor pressure during miction; in addition, the increase in the level of prostate antigen when taking tadalafil is related to taking placebo and is approximately 0.2 mg / ml / year. However, the question of

An interesting multicenter, double-blind, randomized, placebo-controlled study of taking tadalafil 5mg once each day, which took into consideration the standard of the partner’s sex life. The principal assessment criterion for this study was the change between baseline and endpoint erectile function scores, including International Index of Erectile Function (ICEF), Quality of Sex Life (SQoL), and Intercourse Profile. ( cialis 40mg ), Sexual Life Quality Questionnaire (SLQQ) ). The partners were split into groups: patients in one group received placebo (n = 78), the other received tadalafil 5 mg once each day (n = 264) for 12 weeks. The responses of the men and their partners were collected throughout the study. In comparison to placebo, the tadalafil group showed significant improvement in erection efficiency (p < 0.001), including changes in IIEF, two- and three-question ratio profiles. In addition, when taking tadalafil 5 mg once each day, the quality of sexual life of men and their partners SQoL was significantly higher than in the placebo group (p < 0.001). Tadalafil unwanted effects discussion Regarding the the increase in the amount of studies devoted to the constant use of tadalafil in the clinic, there is a discussion about the side effects and complications associated with taking the drug. In his review article, D. Pushkar et al. provides examples of multicenter, randomized, placebo-controlled studies of safe daily tadalafil therapy in men with ED. In a single such study, 184 patients took tadalafil in doses of 5 and 10 mg per day, which only three men stopped taking the drug – in a single case because of headaches and dizziness, and in two cases due to cause of abdominal pain. Many men with ED have concomitant pathology of the heart; the safety of therapy in these patients is particularly relevant. A multicenter study conducted in 36 clinics evaluated the dynamics of cardiovascular diseases when taking tadalafil at a dose of 2 to 50 mg each day or up to 3 times a week. The analysis included 12,487 men (mean age 55 years) with ED treated with tadalafil followed up by 5771 patient-years and 2047 men (mean age 56 years) in the placebo group followed up by 460 patient-years. The analysis excluded patients with premature ejaculation, penile anatomical deformities and prostheses, secondary ED (eg, hypogonadism), unstable angina, myocardial infarction (before 90 days), with systolic blood circulation pressure > 170 or <90 mm Hg. Art. and diastolic blood pressure> 100 or <50 mm Hg. Art. Nitrates have been found in exceptional cases. The duration of the study ranged from 6 to 27.2 months. At the start of the analysis, the structure of concomitant diseases was the following: arterial hypertension – 31%, diabetes – 21%, hyperlipidemia – 17%, coronary heart disease – 5%. Cases of adverse development of cardiovascular events (CVTEAE) were retrospectively analysed: myocardial infarction, sudden cardiovascular and cerebrovascular death. Additionally, patients were divided into risk groups, including obesity, smoking, and over 65 years of age. CVTEAEs per 100 patient-years were calculated by dividing the amount of patients with this particular disease by patient-year (PY) exposure and multiplying by 100. The incidence of myocardial infarction (MI) per 100 patient-years was calculated by dividing the number of patients with MI by the PY exposure and multiplying by 100. Patient exposure-years were determined for each patient and calculated from the date of randomization to the date of completion. The exact 95% confidence intervals for CVTEAE were calculated based on the Poisson distribution. Across all studies, CVTEAEs in tadalafil-treated patients were 0.40/100 patient-years (5771 patient-years of exposure) and 0.43/100 patient-years in the placebo-controlled groups (460 patient-years of exposure ). The data show that the incidence of serious cardiovascular events during the first stages of tadalafil therapy (i.e., 0 to a few months) is comparable to the incidence of CVTEAE during 27.2 months of therapy. In patients taking tadalafil, the incidence of serious cardiovascular events (CVTEAE) ranged from 0.17/100 to 0.54/100 patient-years in placebo-controlled and open-label studies. Incidence rates of CVTEAE were comparable in men with erection dysfunction taking tadalafil to those in patients receiving placebo. Medical research results In conclusion, it ought to be said that the drug tadalafil, that is successfully used for the treating ED on demand, may be used continuously once a day for several months and also years. Evaluations of continuous usage of tadalafil are high, particularly when taking into consideration the interests of both partners and the side effects are comparable to those of placebo. The inclusion of tadalafil in the treatment of LUTS in BPH looks promising, however, further studies are essential to investigate the interaction of the drug with ?-1-adrenergic blockers and 5?-reductase blockers, confirmed by working experience.