Modern erectile dysfunction treatments

ED and diabetes

In the past 10 years, the problem of erectile dysfunction has attracted increasing attention. Erectile dysfunction (ED) is the inability to achieve and (or) maintain an erection necessary for sexual intercourse in more than half of the cases.

ED diabetes along with other complications (diabetic macroangiopathy and neuropathy, retinopathy, etc.) Frequently leads to a significant deterioration in the quality of life of patients, initiates and maintains the depression.

Most men may have similar problems at a certain period of their life, possibly due to overvoltage, stress, and sometimes excessive drinking, so you should not rush to make a diagnosis.

There are three forms of ED: psychogenic, organic and mixed. They differ in treatment approaches and prognosis. Psychogenic ED is associated with a weak desire for sexual intercourse or with its reluctance, depression, anxiety, and therefore is sometimes referred to as “waiting for failure syndrome.” Organic ED is caused by vascular, neurogenic, hormonal disorders, drug exposure, injuries of the penis, etc. The mixed (organ-psychogenic) form is caused by a combination of organic and psychogenic factors. According to R.A. Manusharova, in 80% of cases of ED, its cause is organic and only 20% is psychogenic.

Erectile dysfunction occurs in 50-60% of men with diabetes; The risk of ED in this disease is 3 times higher than in a healthy population. In diabetes there is a significant “rejuvenation” of ED. The frequency of development of ED is directly dependent not only on the age of the patient, but also on the “experience” of diabetes. In approximately 50% of diabetic patients, ED occurs in the first 10 years of the disease, may precede other complications of diabetes, or be their first manifestation.

In diabetes mellitus, a violation of the penile microcirculation occurs, the nerve endings of the penis are affected. Smooth muscle cells that make up erectile tissue are damaged. Vascular diseases, atherosclerosis, and arterial hypertension, which are frequent companions of diabetes mellitus, aggravate   impaired microcirculation and decreased arterial inflow to the penis.

When studying the role of capillary blood circulation using laser doppler flowmetry and other methods, it has been shown that microcirculatory changes can be the cause of vascular impotence even in the presence of normal arterial or venous microcirculation. One of the causes of vasospasm of the penis is smoking.

The probability of occurrence of ED with age, of course, increases, but it is not an inevitable process that accompanies aging. Rather, ED may be due to an altered lifestyle or deterioration in health, which is observed with aging.

Patients with diabetes mellitus type 2, which occurs in most cases in old age, have an age-related decrease in testosterone. It contributes   additional contribution to the development and maintenance of ED, which is not only manifested by a decrease in sexual desire, but also leads to a decrease in the synthesis of NO, the production of which is an androgen – dependent process.

Suggest the psychogenic nature of ED   be patient with the “experience” of diabetes less than 1 year, in which there are no complications, such as diabetic neuropathy, and macrovascular, which can lead to erectile dysfunction. Psychogenic ED is characterized by a sudden onset, intermittent onset, persistence of night and morning erections, the presence of a constant stress factor in the anamnesis; may occur as a result of a change in sexual partner. The organic nature of erectile dysfunction should be assumed in patients with the presence of diabetes mellitus complications. Most men who have an organic cause of ED, an erection disorder is progressive, occurs with all partners, and there is a decrease or complete absence of night and morning erections.

In the structure of organic ED in diabetic patients, its endocrine, neurogenic and vasculogenous forms are distinguished.

The endocrine form of ED may be due to a combination of diabetes mellitus with androgen deficiency. The diagnosis is confirmed by a decrease in testosterone levels, and with its normal content and androgen deficiency, it is necessary to determine the level of the globulin that binds sex steroids to calculate the level of free testosterone in the blood plasma. The cause of ED may also be a pituitary tumor with prolactin overproduction. The neurogenic form of ED should be suspected in the presence of other manifestations of neuropathy. In its early stages, the only complaint may be a feeling of cold in the area of ​​the glans penis. Since the pelvic organs receive autonomous innervation from some sources, a pathology such as bladder and / or intestinal dysfunction may indirectly indicate the neurogenic nature of ED. The vasculogenic form of ED is characterized by the presence of other macrovascular complications, such as ischemic heart disease, arterial hypertension, and the ischemic form of the diabetic foot.

Attention should also be paid to the drug-induced ED associated with the use of medications for the treatment of associated diseases or complications by diabetics. Many drugs adversely affect various parts of sexual intercourse. As a rule, this is due to the blocking of nerve endings providing an erection.

Signs of drug-induced ED are a relatively rapid onset, a temporary connection with taking the drug, a decrease in the severity of the disorder, or its complete disappearance after discontinuation of the drug.

Most often a negative effect on sexual function have antihypertensive agents (diuretics thiazide series, beta – blockers, clonidine) antiulcer (ranitidine, cimetidine) and allergy medications (corticosteroids, theophylline bronchodilators), agents acting on the central nervous system (psychotropics, antidepressants, tranquilizers) and etc.

To understand the main pathological processes that occur when ED, and methods of their correction, we consider the most important links of the physiological mechanisms supporting a normal erection in men:

–        Sexual stimulation causes the release of nitric oxide in the tissues of the penis, which leads to the formation of cyclic guanosine monophosphate (cGMP).

–        The smooth muscles of the penis relax, blood fills the dilated vessels, and an erection occurs.

–        With erectile dysfunction, the picture changes, and the following pathological processes are observed:

–        Cyclic GMP is cleaved by phosphodiesterase-5 (PDE-5).

–        The smooth muscles of the penis contract, its blood vessels constrict, there is an outflow of blood from the cavernous bodies of the penis, and it remains unstressed.

The first stage in the treatment of ED in patients with diabetes mellitus is the maximum compensation of diabetes. ED in men with diabetes mellitus correlates, in addition to age, with the level of glycated hemoglobin (HbA1c), the presence of peripheral and autonomic neuropathy, retinopathy, duration of diabetes. There is a clear correlation of ED with the severity of complications of diabetes. Thus, good control of diabetes mellitus is fundamental to maintaining and maintaining a normal erection.

In the treatment of erectile dysfunction, lifestyle changes are important: physical activity, proper nutrition, stopping smoking and excessive alcohol consumption, weight loss, normalization of the lipid spectrum and blood pressure.

Psychological factors play an important role in all forms of ED. They can both lead to a violation of erection, and layered on the organic cause, which aggravates the course and complicates treatment. Psychotherapy and / or behavioral therapy as an independent treatment can be effective in some patients in the absence of organic causes of ED or as a component of complex treatment. However, very often the listed activities are not enough, and then it is necessary to resort to medication.

The second stage is the drug therapy of ED, the most preferred for patients with diabetes.

Considering that autonomous diabetic polyneuropathy is important in the pathogenesis of ED in patients with diabetes mellitus, alpha- lipoic acid preparations are used as pathogenetic therapy for diabetic polyneuropathy . According to numerous experimental and clinical studies (ALADIN, DECAN, SYDNEY), alpha- lipoic acid preparations are highly effective for the treatment of diabetic polyneuropathy , but randomized studies have not yet been carried out regarding the aspects of the use of alpha- lipoic acid and ED.

In severe diabetic polyneuropathy   and the lack of efficacy of ED treatment, the combination of alpha- lipoic acid preparations with other drugs is advisable.

The main oral medications for the treatment of ED can be divided into three groups: PDE-5 inhibitors; oral α2-adrenoreceptor blockers; toning, fortifying and homeopathic remedies. The effectiveness of α2- adrenoreceptor antagonists, according to a number of randomized studies, slightly exceeds the placebo effect and, according to some estimates, is no more than 30. There are no serious clinical studies of tonic, fortifying and homeopathic medicines.

Thus, among the oral medications used to treat ED, PDE-5 inhibitors, which are erection modulators, are widely used today. They do not directly cause it, but they enhance the relaxing effect of NO through cGMP, blocking PDE-5, resulting in an increase in blood flow in the cavernous bodies of the penis, the emergence and maintenance of physiological erection. A characteristic feature of PDE-5 inhibitors is that they all act only in response to natural sexual stimulation.

Coup in the treatment of ED   made the discovery of sildenafil citrate, which received world fame under the name “Viagra”. The drug is unique in that when taken orally has not so much a system as a local effect. Sildenafil citrate (Viagra) affects mainly the blood circulation of the pelvic organs, is easy to use, it is characterized by high efficacy rates and mild side effects.

After oral administration, the drug begins to act after 30-60 minutes and within 4 hours remains effective in achieving an erection. Once again I want to remind you that the drug acts in response to sexual stimulation.

The recommended dose is 50 mg. It is taken, if necessary, approximately 1 hour before the planned sexual activity no more than once a day. Depending on the efficacy and tolerability, the dose may be increased to 100 mg or reduced to 25 mg. To reduce the traumatic effects of anxious waiting for sexual failure syndrome, it is better to start therapy with sildenafil citrate with a dose of 100 mg with its subsequent decrease to 50 or 25 mg.

It should be remembered that sexual activity itself is fraught with some risk of cardiovascular complications, therefore, before prescribing drugs belonging to the class of PDE-5 inhibitors in men, it is necessary to assess the state of the cardiovascular system and possible physical activity.

Do not treat ED in patients who are contraindicated in sexual activity: in the first 3 months after a heart attack or stroke; with unstable angina or angina occurring during intercourse; severe heart failure that has developed in the last 6 months; uncontrolled heart rhythm disorder; arterial hypotension below 90/50 mm Hg . or uncontrolled arterial hypertension.

A relative contraindication to sexual activity, and consequently, to the appointment of drugs aimed at restoring erection, is the presence of diabetic proliferative retinopathy in a patient with hemorrhages in the fundus, since physical exertion itself can lead to a deterioration of the fundus.

Absolute contraindication to the administration of sildenafil citrate is the intake of nitrates or donators of nitric oxide in any form – orally, in an aerosol or as an injection, since the mechanism of action of sildenafil citrate involves the metabolic pathway of nitric oxide – cGMP , and it was noticed that the drug can enhance the hypotensive action of nitrates.

The effectiveness of sildenafil citrate (Viagra) has been studied in more than 20 clinical trials that were conducted in many countries of the world and covered more than 4,000 men aged 19 to 87 years. In studies conducted in the United States, the pronounced effect of sildenafil in patients with ED and diabetes was confirmed.

In July 2002, a study of sildenafil in men with type 2 diabetes was completed in the UK and other European countries, and its marked efficacy compared with placebo was also established. Researchers note that sildenafil improved erection, even with inadequate glycemic control and the presence of several chronic complications of diabetes.

Nevertheless, sildenafil citrate (Viagra), there are a number of side effects. First of all, it is a headache, nasal congestion, flushing of the face, a change in vision, but, as a rule, they are mild and pass quickly.

In recent years, such drugs from the group of PDE-5 inhibitors, such as tadalafil (Cialis) and vardenafil hydrochloride (levitra). However, it should be noted that their use does not cure erectile dysfunction: when discontinuing therapy, the improvement in erectile function, achieved while taking the drug, does not persist

In patients with reduced testosterone levels in complex treatment of ED, substitution therapy with androgenic drugs is necessary. It is necessary to start a combination therapy with hormonal drugs, since a low testosterone content decreases the effectiveness of PDE-5 inhibitors. Efficacy oftherapies with testosterone preparations with ED, caused by hypogonadism, demonstrated in many studies.

This marked a significant improvement in all components of sexual intercourse. Before the appointment of androgenic drugs, it is necessary to exclude prostate carcinoma. One of the reasons for a temporary or persistent hypogonadal condition is also a violation of the transport of testosterone and its delivery to target organs due to a high level of steroid- binding globulin. In this case, the correction of free testosterone is carried out with Andriol and Sustanon-250, which help to reduce the synthesis of steroid- binding globulin.

Such methods of treatment as the use of vasoactive drugs for intracavernous therapy (alprostadil – Caverject, Edex, papaverine, phentolamine) are not recommended for patients with diabetes mellitus, as in patients with microangiopathy, the frequency of microscopic lesions with the further development of penile fibrosis is high.

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