Treatment Of Erectile Dysfunction In Androgen Deficiency
If a man has a sexual dysfunction due to androgenic deficit, as well as erectile dysfunction (ED), treatment should begin with normalization of testosterone levels. Normalization of androgens by prescription of hormonal drugs (for example, testosterone undekanoate), allows to significantly improve the effectiveness of phosphodietherase inhibitors of type 5 (PDE-5) and the results of ED therapy.
Effect of testosterone on erectile function
Some scientific papers also demonstrate the effect of testosterone on erectile function: after testosterone level recovery, a significantly better response to Sildenafil 100 mg was observed compared to men who took Sildenafil and placebo.
If monotherapy aimed at the elimination of adrogen deficiency is ineffective in relation to the normalization of sexual function, it is reasonable to combine hormonal therapy with vasoactive drugs. It is recommended to start using vasoactive drugs not earlier than 1-1.5 months after restoration of normal testosterone level.
This sequence of treatment is due to the role of testosterone as the main catalyst for sexual arousal – the first and main stage in the emergence of erections. In addition, according to recent data, androgens are involved in the process of maintaining the production of nitrogen oxide (NO2), which is necessary for the emergence of an erection.
Thus, a prerequisite for the effectiveness of PDE-5 inhibitors is a normal male hormonal background, i.e. no androgen deficiency.
Modern concepts of medicine indicate that testosterone is capable of directly affecting the structure of cavernous bodies and nerves. This is confirmed by an experiment on animals, when castration led to a change in the structure of cavernous nerves.
A number of studies have confirmed that the reduction of androgens leads to increased deposition of fat cells in cavernous bodies. This prevents the mechanism of triggering an erection due to venous insufficiency, reduced blood flow and elasticity of the cavernous tissues.
Despite the few observations, it can already be argued that ED treatment in patients with hypogonadism with testosterone drugs leads to the normalization of the structure of the cavernous bodies, improve blood flow and eliminate venous insufficiency, and as a result, the restoration of erection or increase the efficiency of inhibitors PDE-5. Monotherapy with PDE-5 inhibitors is ineffective in such cases.
Substitution therapy with testosterone restores the structure of cavernous bodies, improves blood flow and eliminates venous insufficiency.
Low testosterone level plays an important role in the formation of ED:
- reduces the relaxation of smooth-muscular cells of the cavernous tissue;
- reduced NO2 production;
- increased apoptosis of smooth muscle cells;
- increase in the number of adipocytes;
- reduction of sexual desire.
Since the therapy with vasoactive drugs is symptomatic in nature, i.e., it aims to eliminate symptoms of the disease and does not eliminate the factors causing erectile dysfunction, they are classified as the second type of drugs in the treatment of erectile dysfunction in men with androgenic deficit. Although recently there are new data on the therapeutic effect of Viagra – the most popular representative of the class of inhibitors PDE-5, when administered daily at night on a course regime for at least 1 month.
Of the vasoactive drugs affecting the emergence of erection, preference is given to phosphodiesterase inhibitors of type 5 (Viagra, Cialis, Levitra) as drugs with a sufficiently high efficacy (70-80% depending on the underlying and associated diseases), not declining with prolonged use. Preservation of efficacy and safety of vasoactive drugs in case of long-term use is extremely important, because the symptomatic nature of therapy in case of organic forms of ED suggests their continuous (lifelong) use.
Viagra and generic Cialis are currently drugs that have shown their effectiveness in combination therapy with androgens. To understand the mechanism of action of PDE-5 inhibitors, as well as the role of testosterone in the development of their effect and possible ineffectiveness in reducing testosterone content, it is necessary to know the mechanism of erection.
Mechanism of erection origin
Erection is a vascular reaction that occurs in response to sexual stimulation. A significant role in the complex mechanism of erection is assigned to nitrogen oxide, which is excreted from nerve and endothelial cells in response to sexual stimulation. Nitrogen oxide further diffuses through the membrane of smooth muscle cells and increases the activity of guanylate cyclase, resulting in stimulation of IGMF production in penis tissue. IGMF is an intracellular messenger that affects the reduction of calcium cytosol that stimulates contractile processes. The final result of the action of nitrogen oxide is the relaxation of smooth muscles and an increase in arterial flow.
The destruction of IGMF takes place under the action of a cavernous tissue specific enzyme – type 5 phosphodiesterase. PDE-5 inhibitors show their effect by strengthening the effect of nitrogen oxide released in response to sexual stimulation.
Thus, PDE-5 inhibitors are not stimulants, but erection modulators, as they only strengthen physiological processes aimed at the emergence and maintenance of erection in response to sexual stimulation. In the absence of sexual excitement, observed with a decrease in sex hormones, the prescription of PDE-5 inhibitors is not appropriate, because there will be no “launch” of the mechanism of erection, resulting in the release of NO, increasing the content of cGMF, the concentration of which is maintained by inhibitors of PDE-5, ie, there will be no point of application for the drug action.
Recently, there has been an improvement in prognosis in the treatment of erectile dysfunction in most patients. This is primarily due to the introduction of modern drugs aimed not at the elimination of symptoms (symptomatic treatment), but at the treatment of causes that caused the disease (pathogenetic treatment). In the case of ED, pathogenetic treatment is aimed at eliminating endothelial dysfunction, which is the basis for any form of organic disorders of erectile function.
Such preparations, first of all, include PDE-5 inhibitors and preparations containing analogues of male testosterone hormone, which allow to normalize androgens level and provide good therapeutic base for treatment with PDE-5 inhibitors.
Long course regimen of taking PDE-5 inhibitors is a new practice in the treatment of ED, because previously these drugs were recommended for use during the close proximity of sexual contact. Therapeutic effect in this scheme of treatment is carried out by improving endothelial function, and in some cases leads to complete normalization of sexual function, and subsequent refusal to use the drugs.