Erectile dysfunction (ED)

Having sex extends life, who makes love lives a hundred years. If you have sexual problems, do not be ashamed. Talk to your doctor because serious problems are hidden behind the problem of erectile sexual impotence.

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Il disturbo erettivo: fisiologia dell'erezione e fisiopatologia

Il disturbo erettivo: il trattamento

Quali cure sono efficaci nell'impotenza maschile?

Erectile dysfunction (ED) is a high prevalence disorder that is widespread in the USA, affecting 322 million men by 2025. ED is a widespread condition affecting 13% of the male population. This means that around 3 million Italians have an erectile deficit.

Erectile dysfunction (ED) is associated with many pathologies such as:

- Diabetes mellitus
- Hypertension
- Dislipidemia
- Cardiovascular diseases

The vascular pathologies responsible for erectile dysfunction can be both arterial and venous. In the first case there is a reduced blood supply in the second the blood does not remain in the corpora cavernosa.
At the systemic level, cardiovascular diseases represent one of the main conditions predisposing to erectile dysfunction. It is known that a person with a cardiovascular disease of any kind has a greater risk of developing an erection problem than a healthy person.

Arterial hypertension is a widespread disease responsable of erectile dysfunction in 20% of cases. In males affected by diabetes, DE is present in a percentage ranging from 35% to 75%.

Bochimic mechanisms of erection

The smooth muscle relaxation of the corpora cavernosa necessary for erection is due to a non-adrenergic, non-cholinergic mechanism mediated by nitric oxide (NO), a labile neurotransmitter. Nitric oxide is synthesized from arginine and released from neurons, endothelial cells and possibly smooth muscle cells of the cavernous body of the penis, in response to sexual stimulation. After diffusion to the smooth muscle cells of the corpus cavernosum, NO stimulates the cytosolic enzyme guanylate cyclase to produce a second messenger, the cyclic guanosine monophosphate (cGMP). Cyclic nucleotides, such as cGMP, are hydrolyzed by the cyclic nucleotide isoenzymes phosphodiesterase (PDE), located in various tissues. In the cavernous body of man, the specific PDE-cGMP - type 5 (PDE5) is the predominant isoenzyme. Various studies have shown that the mechanism of the NO / cGMP plays the main role in the relaxation of the smooth muscle of the corpus cavernosum and in the erection of the penis.

Definition

Erectile dysfunction (ED) is defined as the inability to achieve and / or maintain an erection sufficient to conduct satisfactory sexual intercourse. The term erectile dysfunction is better than the term impotence because it more precisely defines the nature of this sexual dysfunction. Erectile dysfunction is frequently classified as: organic, psychogenic, mixed.

Physiology of erection

Erection is a haemodynamic event involving both the central nervous system and local factors. It is regulated by the release of the cavernous arteries and the smooth musculature of the corpus cavernosum. In the state of flaccidity, sympathetic innervation produces a tonic contraction of the smooth muscles of the arteries, reducing the flow of blood. Central psychogenic stimuli and / or sensory stimuli from the penis increase parasympathetic activity and reduce sympathetic activity; hence a smooth muscle relaxation of the penis and an increase in blood flow through the cavernous arteries and helicopters. Smooth muscle relaxation increases the distensibility of cavernous spaces, leading to erection.
The increase in blood volume and the compression of the trabecular smooth muscle released against the relatively rigid tunica albuginea tunic reduces the venous flow at the outlet (veno-occlusive mechanism).

Causes of erectile dysfunction

The mechanism of erection can be altered by multiple factors.
The causes that can determine the onset of erectile dysfunction are divided into psychogenic, endocrine, neurogenic, vascular (arterial and venous), pharmacological, surgical, radiotherapeutic and predisposing conditions

The main causes of impotence are divided into:
Psychogenic
Anxiety - Couple problems - Depression - Stress
Endrocrine
Testosterone Reduction - Increased Prolactin
Neurogene
Multiple sclerosis - Parkinson's disease - Alzheimer's disease - Spinal lesions
Vascular
Atherosclerosis - Dyslipidemia - Diabetes - Hypertension
pharmacological
Sedatives - Antihypertensives - Antidepressants - Hormones
Habits of life
Smoking - Alcohol - Drugs

The ED provides therapy with drugs such as viagra, cialis, levitra, inhibitors of 5- (PFE-5), including vardenafil which is now an effective therapeutic option, well tolerated and well accepted by the patient. The PDE-5 enzyme degrades the guanosine monophosphate cGMP, in the cavernous body of the penis, and interferes with the pathway mediated by the cGMP, responsible for the physiological changes required for erection. As a result, inhibition of this enzyme causes an improvement in the erection. Vardenafil is a potent and selective PDE-5 inhibitor with widely demonstrated efficacy and tolerability in randomized, double-blind, placebo controlled trials in patients with ED, including those with co-morbidities. The RELY-1 study conducted between June 2003 and January 2004 in 42 centers in Europe, Asia and North and South America assessed whether the enrolled patients could perform 4 sexual intercourse on a regular basis over 4 days. Subjects who were> 50% unsuccessful were included in the assessment phase during which they should have sexual intercourse by taking the pill one hour before intercourse, ie 10 mg of vardenafil; it was necessary to evaluate by SEP-2 and SEP-3 questionnaire whether the relationship had been possible and the erection maintained over time and, therefore, if the drug had had unpleasant effects. The patients enrolled were all heterosexual with DE diagnosed for at least 6 months and they must have had a failure in at least 50% of sexual intercourse.

Results.
Of the 600 subjects who were given the 10 mg dose of vardenafil in the evaluation phase, 32% were hypertensive, 16% diabetic and 19% dyslipidemic; moreover 4% had hypertension and diabetes. The average age was 54 and the erigendi impotence averaged 3.3 years.

Effectiveness.
Of the 600 patients treated with 10 mg vardenafil dose, 87% had a complete erection with penetration and 443, ie 73% had successfully completed sexual intercourse. At the end of the study, ie after 12 weeks, compared to those who took placebo (a pill without medicine) those treated with vardenafil were successful in 77% against 42% of the other group. So great success in treatment and high efficacy, but 5% of patients felt hot flashes, headache and dyspepsia.
Pharmacological causes
Some classes of medications such as antihypertensives, psycho-drugs and hormonal therapies cause erectile dysfunction.
Surgical Causes
Radical prostatectomy (removal of the prostate and seminal vesicles) due to tumor and radical cystectomy (bladder removal) for bladder carcinoma are the main causes of post-surgical erectile dysfunction. Pelvic radiotherapy is also an important risk factor. In the literature there are data of erectile dysfunction secondary to radiotherapy ranging from 30 to 85% of treated patients.
Habits of Life
Smoking is one of the causes of DE. In comparison to non-smokers, smokers have a higher risk of developing an ED. The association of smoking with other risk factors such as diabetes also increases the likelihood of developing an ED. Other predisposing conditions are sedentary life, obesity, chronic alcoholism and drug use.

Oral therapy of erectile dysfunction

Pompei-Italy - Mercury-Priapus exhibits his enormous penis as the guarantor of fecundity and as a possible punishment

Phosphodiesterase type 5 inhibitors (PDE5), mark the beginning of a new era in the pharmacological therapy of erectile dysfunction. In physiological conditions, one of the main positive mediators of the erection phenomenon is Nitric Oxide (NO); the latter is released from the nerve endings and then spread into the smooth muscle of the corpora cavernosa, where it activates the enzyme guanylate cyclase which synthesizes cGMP, an intracellular mediator that allows the relaxation of the smooth muscle of the cavernous bodies, leading to the appearance of penile tumescence. finally to the erection. The mechanism of action is characterized by the inhibition of the enzyme PDE5 which involves the increase of the intracellular levels of the neurotransmitter NO, playing the role of peripheral facilitator of the erectile mechanism.

Sildenafil, administered orally at 25, 50 and 100 mg dosages, is rapidly absorbed, reaching a maximum plasma concentration within one hour of fasting oral intake. Sildenafil is metabolized by cytochrome P450 3A4 so that drugs that inhibit this isoenzyme (cimetidine, ketoconazole, erythromycin) may cause an increase in plasma drug levels. The administration of inhibitors is absolutely contraindicated in patients taking nitroderivatives. The main side effects reported by the majority of patients are generally mild-moderate transient and in particular are represented by transient headache (15.8%), flushing to the face (10.5%) and dyspepsia (6.5 %).

Tadalafil belongs to the class of PDE5 inhibitors but offers a very special pharmacokinetic action, given the totally different chemical structure compared to sildenafil and vardenafil. The drug is rapidly absorbed after oral administration and has a plasma half-life of 17.5 hours, a characteristic that differentiates it considerably from all other molecules belonging to the same pharmaceutical category. It can be administered independently of food or alcohol intake. The fastest action of tadalafil is obtained 20 minutes after intake and the response period is extended up to 36 hours. Similarly to sildenafil, tadalafil also enhances the hypotensive effects of nitroderivatives, which are contraindicated for use in patients who take such medications simultaneously. The most common reported side effects were dyspepsia, headache and low back pain, but with increasing doses (20 mg) the tolerability was substantially unchanged

The vardenafil represents another drug for the oral therapy of erectile dysfunction also belongs to the class of PDE5 inhibitors. The concentration of vardenafil able to inhibit 50% of the activity (IC50) of the isolated PDE5, was equal to 0.7 nmol / L compared to 6.6 nmol / L for sildenafil, a difference of about 10 times which explains the superior pharmacological potency of vardenafil. The drug is rapidly absorbed and peak plasma concentrations were reached less than an hour after taking a 10 mg dose. The maximum plasma concentration increases linearly and the elimination half-life is around 4.8 hours. Adverse events verified after vardenafil use are those commonly associated with PDE5 inhibitors: headache, flushing, dyspepsia and rhinitis, all of which are dose-dependent and of mild to moderate intensity.

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