Effects of testosterone on erectile function: implications for the therapy of erectile dysfunction

Sexual potency declines with age, as does the efficiency of erection. Many studies show that different patterns of erectile dysfunction (ED), varying from occasional inability to obtain a full erection, impairment throughout intercourse and total absence of erectile response, might not be triggered by psychological factors only. Recent research indicates that ED relies on organic causes, and has challenged the development of new therapies. One therapeutic approach in patients who have testosterone deficiency is based on androgen therapy. Thus, we reviewed data on testosterone-induced effects relative to erectile function, summarizing the results from studies reported in 1991-2006 on testosterone therapy in patients with ED and hypogonadism, with a special focus on men not responding to phosphodiesterase-5 (PDE-5) inhibitors. We searched several computerized databases parallel with printed bibliographic references. Many studies have established animal models, which confirm that testosterone is important in modulating the central and peripheral regulation of ED. Testosterone deprivation has a strong negative impact on the structure of penile tissues and erectile nerves, which can be prevented by androgen administration. Combined therapy regimens with PDE-5 inhibitors and testosterone might improve ED in patients with hypogonadism of different causes. Thus, androgen treatment in hypogonadic patients, including those unresponsive to PDE-5 inhibitors, often results in an improvement of ED. Testosterone therapy is safe and convenient, while rapidly correcting low testosterone levels.     

The ageing penis

Epidemiological reports have demonstrated the determinant role that age plays in the pathophysiological mechanism of an erection. The atherosclerosis of the penis and its ischaemia that occurs with ageing impacts directly on the intracavernous structures and the erectile physiologic function. The effects of testosterone on libido and sexual behaviour are well established but its function in the erectile mechanism remains unclear. In the animals, testosterone deficiency seems to provoke a decrease in smooth muscle content and nitric oxide (NO) production. In human, testosterone seems to affect the central system rather than the peripheral mechanism of an erection. The role of ischaemia and the decrease in testosterone in the mechanism of erectile dysfunction are reviewed.     

雄激素缺乏与勃起功能障碍

雄激素可通过增强性欲、性唤起等间接促进阴茎勃起,在维持阴茎正常的勃起组织结构方面起重要作用。睾酮缺乏可导致小梁平滑肌减少、细胞外基质增多、白膜下脂肪细胞沉积等。勃起时,阴茎组织的上述改变可引起静脉闭塞不全而发生静脉漏,从而出现勃起功能障碍;睾酮还可影响一氧化氮合酶(NOS)、RhoA/Rho激酶的表达及活性从而直接影响阴茎勃起。对单用磷酸二酯酶5(PDE5)抑制剂无反应的性腺功能减退的ED患者补充睾酮可收到良好的治疗效果。     

Hormonal etiology in erectile dysfunction

The proper function of erection mechanisms depend on correct interrelationship between psychological, vascular, neurological and hormonal factors. Endocrine diseases affect sexual function, and sexual dysfunction may be one of the symptoms of some hormonal anomalies. Diabetes mellitus is the endocrine disease most frequently causing erectile dysfunction due to the frequent vascular and neurological complications associated. It is important to determine blood glucose in the initial evaluation of a male with erectile dysfunction, as well as to try an adequate control of blood glucose levels to avoid worsening. Diabetic male erectile dysfunction is multifactorial, more severe and has worse response to oral treatment. Hyperprolactinemia causes disorders of the sexual sphere because it produces a descent of testosterone. In these cases, sexual symptoms are treated by correcting the levels of prolactin. Routine determination of prolactin is not clear and it seems it should be determined when testosterone levels are diminished. Thyroid hormone disorders (both hyper and hypotyroidism) are associated with erectile dysfunction, which will subside in half the patients with thyroid hormone normalization. The role of adrenal hormones in erectile function is not clear and their routine determination is not considered in the diagnostic evaluation of erectile dysfunction. The role of estradiol in the regulation of the erection mechanism is not well known either, although it is known that high levels may cause erectile dysfunction. Among endocrine-metabolic disorders we point out dyslipemias, with hypercholesterolemia as an important risk factor for erectile dysfunction and, though its correction may prevent vascular system deterioration, the role of statins in erectile dysfunction is not clear.     

The Role of Andorgens in the Erectile Response: A 1999 Perspective

Evidence from several laboratories strongly supports a critical role for androgens in the maintenance of the mammalian erectile response. In animal studies, androgens appear to act at the end-organ level (i.e., corporal tissue and vasculature), as well as in the portions of the nervous system which mediate erection. Particularly in the rat model, androgens act centrally to support copulatory behavior and peripherally to maintain the production of nitric oxide and support the veno-occlusive mechanisms. Other studies suggest that alternative, non-NO-dependent, pathways may also be androgen sensitive. However, despite this expanding knowledge base about how androgens act in the erectile response in laboratory animals, the recent studies have not greatly clarified the role of androgens in human penile erection. There does not seem to be a strong cause and effect relation between blood androgen concentrations and erectile function; even in severely hypogonadal men, the erectile response is not always lost, and testosterone treatment of hypogonadal men with erectile dysfunction does not necessarily restore lost erectile function. In addition, different types of erection (nocturnal, in response to visual sexual stimulation, in response to sexual partner) may require different degrees of androgenic support.     

The relationship between hypogonadism and erectile dysfunction

It is well known that testosterone enhances sexual interest leading to an increased frequency of sexual acts and an increase in the frequency of sleep-related erections. However, it has little effect on fantasy- or visually induced erections. Exact contribution to erection from testosterone in men remains unclear. Animal studies have well demonstrated that testosterone plays critical physiological (activity of nitric oxide synthases and phosphodiesterases), biochemical (through an endothelial-independent pathway and adrenergic tonicity) and structural (change of fibroelasticity and hollow cell accumulation) roles in erectile function. The supplementation of testosterone to castrated animals can restore erectile function. Clinically, reports of patients with erectile dysfunction (ED) combined with hypogonadism who receive testosterone therapy have inconsistent results. However, testosterone may ameliorate the expression of the phosphodiesterase-5 (PDE5) inhibitor, and the use of testosterone in conjunction with the PDE5 inhibitor revealed convincing results. Because of potential risks in clinical use, testosterone therapy should be individualized, carefully considered and closely monitored, especially, in patients with possible occult prostate cancer, and large benign prostatic hyperplasia. Lower urinary tract symptoms might be worsened by this treatment, since the prostate is an androgen-dependent tissue.     

Dramatic improvement of penile venous leakage upon testosterone administration. A case report and review of literature

The main effect of testosterone was long-time assumed to be on sexual interest and, indirectly, on erectile function. Newer insights demonstrate that testosterone deficiency impairs the anatomical, ultrastructural, biological and physiological/functional substrate of penile erection, which can be, at least in part, restored by normalization of plasma testosterone levels. This is a report on a 56-year-old man suffering from diabetes mellitus type II and metabolic syndrome, who had complaints of a severe erectile dysfunction because of venous leakage, confirmed by pharmaco-cavernosography. He was also testosterone deficient (1.8 ng ml(-1)). Upon testosterone administration his erectile function improved dramatically. Repeated cavernosography no longer showed venous leakage.     

Die endokrine Basis von sexuellen Funktionsstörungen im Alter

There are no direct associations between testosterone levels and sexual function in the aging male. A study of 169 patients focusing on the relations of hormone levels and sexual dysfunction did not reveal associations between testosterone levels and the risk of altered sexual functions. In volunteers, in whom a hypogonadism was generated by the application of GnRH, no alteration in sexual reactions occurred. It is possible that other testosterone fractions are more meaningful than the total testosterone. However, all the known fractions correlate closely. The significance of a normal testosterone level for a normal erection has been rarely considered up to now. In an animal experiment, the intracavernous pressure, the density of α-receptors, and the PDES activity depended on normal testosterone levels. It is not known whether different testosterone levels influence the effectiveness of treatment procedures for erectile dysfunction in humans. The following questions with practical consequences have to be answered: Is the extensive determination of the bioactive testosterone necessary? Does the efficacy of treatment for erectile dysfunction depend on testosterone levels?     

The association between elevated serum oestradiol levels and clinically significant erectile dysfunction in men presenting for andrological evaluation

The goal of this study was to investigate the association between serum oestradiol levels and clinically significant erectile dysfunction in a cohort of men presenting for andrological evaluation. Retrospective review was conducted of patients that presented to a urologist with practice in andrology over an 18‐month period. Patients completed the Male Sexual Health Questionnaire and had serum total testosterone and oestradiol measurements prior to 10:30 a.m. via immunoassay. t Tests, chi‐square tests and multivariate logistic regression were used to compare clinical characteristics between those with adequate erectile function (erection scale score > 2) vs. clinically significant erectile dysfunction (erection scale score ≤ 2). Among 256 patients, average age was 49 years (SD 15), average serum oestradiol was 22.3 pg/ml (SD 10.6), and average serum total testosterone was 465.9 pg/ml (SD 206.3). On multivariate logistic regression, serum oestradiol was associated with clinically significant erectile dysfunction (OR 1.52 per SD increase, 95% CI 1.11–2.09, p = 0.009) when controlling for serum total testosterone, age, body mass index and smoking status. These results warrant future studies on the utility of measuring serum oestradiol in patients with erectile dysfunction and the use of aromatase inhibitors in patients with erectile dysfunction and elevated serum oestradiol.     

Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold

Androgens play an important role in erectile function. However, the dose-response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%-12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.     

Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter-dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.     

Hypogonadism and erectile dysfunction: the role for testosterone therapy

The role of low testosterone levels in erectile dysfunction (ED) remains unclear. Both organic and psychogenic factors contribute to ED, with vasculogenic causes being the most common etiology. Approximately 10-20% of patients with ED are diagnosed with hormonal abnormalities. At the physiologic level, two second messenger systems are involved in mediating erections, one involving cyclic adenosine monophosphate (cAMP) and the other involving cyclic guanosine monophosphate (cGMP). PDE5 inhibitors such as sildenafil promote the cGMP pathway, while alprostadil affects the cAMP pathway. Evidence is strong that, in animal systems, testosterone has direct effects on erectile tissue. However, although testosterone clearly has an impact on libido in humans, its effect on penile function is less clear. Evaluation of ED includes medical, sexual, and psychosocial history assessments, as well as laboratory tests to check for diabetes and hormonal abnormalities. Initial interventions should involve correction of potentially reversible causes of ED, such as hypogonadism. First-line therapy for other patients is typically oral PDE5 inhibitors, such as sildenafil, tadalafil, or vardenafil. For patients who fail treatment with PDE5 inhibitors, local therapies such as intracavernous alprostadil are highly successful. Recent data also support the success of combination therapy with sildenafil and testosterone. This opens the possibility of other combinations of testosterone and other treatments of ED. The ability to exploit multiple pathways in the physiologic processes leading to erection may help improve therapy for ED.     

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats

What’s known on the subject? and What does the study add? Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter, and our previous study found that the mRNA expression of VIP was independent of androgens. The present study further investigated the vivo effect of VIP on erection. We found that not only the expression of VIP was independent of androgens, but also the effect of VIP on erection was independent of androgens. In fact, we found that VIP played a more significant role on erection in castrated rats than in normal rats.

OBJECTIVE

• ? To investigate the regulatory role of androgen in VIP‐mediated erectile effect. Androgen is essential for physiological erection. Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter. While previous studies demonstrated that VIP expression in the penis was androgen‐independent, it remains controversial whether androgen has any effect on VIP‐mediated erection.

MATERIALS AND METHODS

• ? Male SD rats were divided into a control group, a castration group, and a castration‐with‐testosterone‐replacement group. Four weeks later, each group was subdivided into low and high‐dose VIP subgroups and subjected to intracavernous injection of 0.5 and 2 µg VIP, respectively.
• ? Erectile function was tested by recording intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) before and after VIP injection.
• ? The expressions of the VIP‐receptor (VPAC2), G‐protein stimulatory and inhibitory alpha subunits (Gs‐α, Gi‐α), and PDE3A in rat corpus cavernosum (CC) was qualified by real‐time PCR and Western blot analysis.

RESULTS

• ? Castration reduced erectile function while testosterone restored it. VIP improved erectile function in a dose‐dependent manner.
• ? High‐dose VIP significantly enhanced erectile function in castrated rats and there was no difference of ICP/MAP among three groups after injection of high‐dose VIP.
• ? Low‐dose VIP also resulted in a higher improvement of erectile function in castrated rats, although the ICP/MAP was lower in these rats than in the other two groups. VPAC2 and Gs‐α were up‐regulated while Gi‐α and PDE3A were down‐regulated in CC of castrated rats.

CONCLUSION

• ? VIP improves erectile function much more significantly in hypogonadal condition, mainly due to the higher expression of VPAC2, Gs‐α, and lower expression of Gi‐α and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect of VIP.

     

Effect of increased prolactin and psychosocial stress on erectile function

Sexual dysfunctions in men are complex disorders that consist of organic and psychogenic components. The most common sexual dysfunction is erectile dysfunction. It is the inability to achieve or maintain an erection for satisfactory sexual performance. This disorder can be caused by high blood pressure, heart disease, vascular problems, psychological and hormonal factors such as problems with testosterone and prolactin levels. In this study, we tested the relationship between erectile dysfunction, hyperprolactinemia and psychosocial stress. Clinical examinations of 60 patients with erectile dysfunction, which also included psychosocial stress, focussed on patient history, comprehensive sexological examination, biochemical analyses of serum prolactin, total testosterone and thyroid-stimulating hormone with psychometric evaluation of erectile function and a checklist of trauma symptoms (TSC-40). The results show significant Spearman correlations of psychometric evaluation of erectile function with prolactin (R = .50) and results of the trauma checklist score (R = .55) and significant Spearman correlations between TSC-40 and prolactin (R = .52). This result indicates a significant relationship between erectile dysfunction, hyperprolactinemia and stress symptoms in men.     

Relationship between penile erection and the ratio of estradiol to testosterone: A retrospective study

Previous studies have found that the ratio of estradiol to testosterone (E2/T ratio) has a negative effect on sexual function, but the relationship between the E2/T ratio and erection of the penis is not clarified. We conducted a retrospective study of 183 patients with erectile dysfunction and 52 healthy men to investigate the relationship between penis base erection and tip erection. All participants underwent nocturnal penile tumescence tests and medical history checks and had relevant biochemical and endocrine indicators measured. The ratio of estradiol to testosterone was calculated. The relationship between E2/T ratio and erectile time of penile tip and penile base was determined by univariate analysis, multivariate analysis and stratification analysis. After adjusting for mixed factors, the results showed that the E2/T ratio had a more significant negative effect on the base of the penis compared with the tip of the penis (Hazard ratio: −4.34 95% CI: −6.52, −2.16 p = .0001). Moreover, when the effective erection time was ≥10 min, the negative effect of E2/T on penile root erection was more obvious (HR ratio: −4.46 95% CI: −6.50, −2.43 p < .0001). In summary, our study demonstrated a negative relationship between E2/T ratio and penile erection, particularly at the root of the penis.     

硫化氢与阴茎勃起功能关系研究进展

硫化氢(H2S)是继NO和CO之后第3种被发现的具有内源性活性的气体信号分子,在哺乳动物体内H2S主要由两种蛋白酶———胱硫醚-β-合酶(CBS)和胱硫醚-γ-裂合酶(CSE)合成产生。H2S在体内具有重要的生理调节功能,它可作用于ATP敏感性钾离子通道(K+-ATP)舒张血管平滑肌,与睾酮及NO协同作用舒张阴茎海绵体平滑肌,促进阴茎勃起等。目前,治疗勃起功能障碍(ED)主要应用选择性的5-型磷酸二酯酶(PDE5)抑制剂,而临床发现PDE5抑制剂对部分ED患者治疗无效,因此,进一步研究H2S在阴茎勃起过程中的调节机制及作用,可能为ED提供了新的治疗途径。     

Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil

BACKGROUND: We retrospectively evaluated the erectile function after nerve-sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function. METHODS: We evaluated 48 Japanese patients who underwent nerve-sparing RRP at the Sapporo Medical University School of Medicine, Sapporo, Japan, between January 1996 and December 2001. Erectile function following nerve-sparing RRP was assessed by a simple mailed questionnaire that was constructed for the study. RESULTS: Of the 48 patients, 36 had normal erectile function preoperatively, but for 12, function was not sufficient to penetrate. The overall estimated recovery rates of any degree of erection were 50.6% at 36 months and 94.3% at 60 months. However, that of erection sufficient to penetrate was only 17.7% at 36 months and was only seen in bilateral nerve-sparing patients. Sildenafil was effective in 9 of 13 ED patients (69.2%) in both nerve-sparing groups. When patients were divided according to preoperative erectile function, no difference was found in the efficacy rate between patients with normal function and those with ED. CONCLUSIONS: Even bilateral nerve-sparing RRP can not always guarantee a sufficient erection. However, sildenafil is effective for ED following nerve-sparing RRP regardless of the nerve-sparing procedure or preoperative erectile function. Thus, preoperative function alone, although depending on its severity, may not necessarily be a reason for exclusion from receiving nerve-sparing RRP if patients want to have the operation.     

Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone

To investigate the therapeutic effect of androgen on hypogonadal patients unresponsive to sildenafil alone. In total, 32 hypogonadal patients with erectile dysfunction (ED), initially had an inadequate response to sildenafil (100 mg). Oral testosterone undecanoate (Restandol, 80 mg, bid or tid) alone was supplied for 2 months, and if patients could not achieve a satisfactory erection, combined use of testosterone and sildenafil was continued thereafter. Total testosterone (TT), free testosterone (FT), and the parameters of the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), and uroflow rate (UFR) were assessed. Eleven patients (34.3%) achieved satisfactory erectile function after testosterone replacement only. Another 12 (37.5%) patients experienced satisfactory intercourse after combined therapy. Serum TT and FT levels significantly increased after the use of testosterone alone (415+/-163 vs 220+/-101 ng/dl, P<0.01; 10.4+/-4.6 vs 5.1+/-1.9 ng/dl; P<0.01, respectively) and the combined use of testosterone and sildenafil (498+/-178 vs 220+/-101 ng/dl, P<0.01; 11.7+/-4.6 vs 5.1+/-1.9 ng/dl, P<0.001, respectively); as did the IIEF score (14.8+/-6.8 vs 12.6+/-7.5, P<0.01, 17.5+/-5.2 vs 12.6+/-7.5, P<0.001, respectively). However, no statistical differences were demonstrated for IPSS or UFR. In conclusions, one-third of hypogonadal patients with ED who failed to respond to sildenafil, responded to testosterone alone, another third responded to sildenafil again after normalization of testosterone. So, in hypogonadal patients with ED, androgen supplementation is first-line therapy. If patients are unresponsive to androgen alone or sildenafil alone, combined use may improve erectile function and enhance the therapeutic effect of PDE-5 inhibitors.     

Testosterone and erectile dysfunction

The role of testosterone on sexual desire, interest and motivation is well established, but its effects on erectile function remain controversial. Animal data show that experimental or medical castration results in loss of the intracavernosal pressure, smooth muscle/connective tissue balance, and penile tissue concentration of nitric oxide synthase-containing nerves, which alter the fibroelastic properties of penile tissue compliance, leading to veno-occlusive dysfunction and therefore erectile dysfunction. Castration also induces apoptosis of penile erectile tissue, and new DNA synthesis is induced by treatment with testosterone. In an animal model of venogenic erectile dysfunction, intracavernous vascular endothelial growth factor (VEGF), in addition to testosterone, restores the smooth muscle/connective tissue balance, endothelial cell hypertrophy and hyperplasia and normalizes the diameter of the dorsal nerve fibres, thereby preventing veno-occlusive dysfunction. There is some evidence that treatment with testosterone may be beneficial to men with erectile dysfunction who have low baseline testosterone levels. Androgens may also control the expression and activity of phosphodiesterase type-5 (PDE-5) in the penile corpus cavernosum. Oral drug therapy with PDE-5 inhibitors fails in some patients with erectile dysfunction. However, when testosterone is used together with a PDE-5 inhibitor, sexual function is restored in these patients, creating the potential for pharmacological combination therapy with testosterone for the treatment of erectile dysfunction.     

Evaluation of transurethral application of alprostadil for erectile dysfunction in Indonesians

Aim: To evaluate the efficacy and safety of transurethral application of alprostadil (MUSE.) for the treatment of erectile dysfunction in Indonesians. Methods: Twenty erectile dysfunction patients aged between 32 - 74 years old were recruited in this study. The inclusion criteria were as follows: 1 ) adult males 18 years or older with a subjective complaint or erectile dysfunction, 2) to provide written informed consent, 3) to agree not to use other forms of treatment for erectile dysfunction, 4) fulfill the screening laboratory values. Part 1, eligible patients were titrated in the clinic starting with a dose of 250 μg and proceed in a stepwise manner to 500μg and 1000μg on separate clinic visits until they identified a dose that produced a satisfactory response. The interval between each in-clinic titration was 2-3 days. Each in-clinic titration dose was evaluated at 15 min intervals over a one hour period for erection assessment, blood pressure and pulse. Part 2, patients used MUSE at home for three months at the dose identified during the inclinic titration. Monthly interim visits were required for patient follow-up and drug distribution. At the end of the study, patients had another laboratory (except testosterone, only assayed in screening procedure) and physical examination. Results: The etiology of erectile dysfunction was psychological in 5 patients and organic in 15 patients. The 65% of the patients achieved the erection scale of 4 or 5 either in the clinic or at home, 10% achieved the scale of 4 at home, but not in the clinic, and 25 % only achieved the scale of 2 or 3 with the highest dose of 1000μg either in the clinic or at home. No significant differences were found in biochemical examination before and after the study. The 60 % of the patients who achieved erection scale 4 or 5 continued to use MUSE until the end of the study, while 40 % of them complained of pain at the time of MUSE application, during erection and/or during intercourse. They withdrew from the study. Conclusion: Transurethral application of alprostadil (MUSE) is effective and safe to produce erection sufficient for intercourse in erectile dysfunction of various etiologies. Pain during application, erection and intercourse is a common side effect and a cause of withdrawal.