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Antonio Aversa

Publications and source records attributed to Antonio Aversa.

12 recordsLinked to original sources
PubMed2006

Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences.

INTRODUCTION: Erectile dysfunction (ED) and decline of testosterone levels are frequently observed with age and also in illnesses with a common basis of endothelial damage. OBJECTIVES: To review molecular mechanisms underlying androgen action upon its receptor and phosphodiesterase type 5 (PDE5) expression and regulation by testosterone in cavernous tissue and their clinical implication in the treatment of ED refractory to PDE5 inhibitors (PDE5-Is). METHODS: From January 2003 to May 2006 [corrected] we performed an extensive, unsystematic MEDLINE literature search reviewing relevant data on basic and clinical studies regarding the efficacy of combination therapies. RESULTS: Most trials using testosterone alone for treatment of ED in hypogonadal men suffer from methodologic problems and report inconsistent results, but overall the trials suggest that testosterone is superior to placebo. Orally effective PDE5-Is, such as sildenafil, tadalafil, or vardenafil, may be ineffective depending on the demonstration of testosterone regulation of PDE5 expression in human corpus cavernous, and their efficacy may be enhanced by testosterone adjunction whenever necessary. CONCLUSIONS: Screening for hypogonadism in all men with ED is necessary to identify men with severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment. Identification of threshold values for testosterone supplementation to appropriately benefit from PDE5-Is failure may improve clinical management of unresponsive patients with minimization of unwanted effects.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

The penile vasculature in systemic sclerosis: A duplex ultrasound study.

INTRODUCTION: Systemic sclerosis is a connective tissue disease characterized by Raynaud's phenomenon, degenerative changes and vascular lesions in the presence of thickened, sclerotic skin lesions determined by cellular proliferation, and excess of extracellular matrix production. The role of ultrasound in the investigation of penile pathology is well established as vasculogenic impotence accounts for more than 30% out of overall causes. AIM: In this article, we report for the first time the extent of penile vascular damage in a series of 15 sclerodermic patients (mean age 47 +/- 12.5 SD) under current treatment for their disease irrespective of their sexual dysfunction complaints. METHODS: After disease classification (mean duration of disease 7.2 +/- 5.1 years), all patients were interviewed about the presence or absence of erectile dysfunction (ED) by using the Sexual Health Inventory for Men (SHIM) questionnaire, and then blood flow velocity in the cavernous artery following standardized pharmacostimulation was determined with Duplex ultrasonography along with the intima media thickness (IMT) of the common carotid artery, a valid index for atherosclerosis. RESULTS: Mean SHIM scores revealed the presence of moderate-to-severe ED (mean 13.3 +/- 6.3). Interestingly, in all patients diffuse hyperechoic "spots" inside the corpora cavernosa along with thickening of the tunica albuginea were found. Severely impaired mean peak systolic velocities (20.2 +/- 5.5 cm/second) in the presence of mild venous leakage as expressed by mean end diastolic velocities (4.6 +/- 2.9 cm/second) were found along with normal IMT (0.065 +/- 0.010 cm) and acceleration time (92.3 +/- 32.7 cm/second). CONCLUSION: Penile fibrosis almost invariably occurs in sclerodermic patients and this determines incomplete penile arterial and smooth muscle cell relaxation and ED despite the absence of indirect signs of early atherosclerosis, that is, abnormal IMT and acceleration time.

Adult↗
PubMed2006

Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study.

INTRODUCTION: It has been reported that lack of sexual activity due to erectile dysfunction (ED) may be associated with testosterone (T) decline. AIM: To investigate whether the known changes in sex hormones associated with resumption of sexual activity are sustained in the long term. MAIN OUTCOME MEASURES: Primary endpoints were variations from baseline of steroid hormones: total T, free T (f T), and estradiol (E). Secondary endpoints were variations of erectile function domain scores at International Index of Erectile Function-5 (IIEF-5). METHODS: In an open-label fashion, 20 patients (mean age 54.8 +/- 8.4 years) received tadalafil 10-20 mg on demand for 12 months. Exclusion criteria were those reported for phosphodiesterase inhibitors, including hypogonadism and hyperprolactinemia. RESULTS: Tadalafil assumption was safe and well tolerated (overall adverse effects in 15% of patients) and none discontinued medication. A significant decrease in E levels occurred at the end of the study (from 19.9 +/- 9.6 to 16.6 +/- 8.1 ng/dL, P = 0.042 vs. baseline), with parallel increase in the T:E ratio (26.3 +/- 15.3 to 32.6 +/- 17.7, P = 0.05), whereas no changes in T and f T serum levels were observed, respectively (411.4 +/- 131.4 to 434.2 +/- 177.1 ng/dL and 47.7 +/- 15.3 to 49.9 +/- 19.1 pmol/L, not significant). Interestingly, nonparametric subgroup analysis for related samples revealed that E decrease was detectable only in lean (N = 14) but not in obese (N = 6, body mass index > 27.5 kg/m2) subjects (17.8 +/- 10.1 vs. 13.5 +/- 6.8, P < 0.05). A net increase in IIEF-5 scores was observed at the endpoint (13.7 +/- 5.9 vs. 25.7 +/- 2.9, P < 0.0001). CONCLUSIONS: Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil might have a role in the regulation of erectile function.

Adult↗
PubMed2006

Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction.

Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothelial function and, erection is a basically vascular event that necessitates an intact endothelium to occur. Hence, ED may be mostly considered as the clinical manifestation of a disease affecting penile circulation as a part of a generalized vascular disorder due to atherosclerosis. Orally active drugs, i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of on-demand drugs licensed for ED treatment and appear to offer advantages over past therapies in terms of ease of administration and cost, and they are now widely advocated as first-line therapy. The recent discovery that chronic not on-demand administration of these drugs may improve erectile and endothelial response in men previously unresponding to on-demand regimes, opens a new scenario in the treatment of men with ED and comorbidities. Finally, the recent approval of PDE5-i sildenafil for the treatment of pulmonary arterial hypertension represents the new challenge for these class of drugs. Aim of this article will be to provide an update on the pathophysiology of ED and how to use of different available PDE5-i in approaching sexual dysfunctional men, pointing out on their characteristic of efficacy and safety and different indications in special sub-populations.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.

OBJECTIVE: Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. METHODS: We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. RESULTS: At 4 weeks, FMD was significantly improved by TAD (from 4.2+/-3.2 to 9.3+/-3.7%, p<0.01 vs. baseline), but was not modified by PLB (from 4.1+/-2.8 to 4.0+/-3.4%, p=NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1+/-3.9% vs. 4.2+/-3.2%, p=0.01 vs. baseline; 9.1+/-3.9% vs. 9.3+/-3.7%, vs. 4 weeks, p=NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2+/-12.3 vs. 52.6+/-11.7 and 51.1+/-3.1, p<0.05) and a decrease in endothelin-1 levels (3.3+/-0.9 vs. 2.9.+/-0.7 and 2.9+/-0.9, p<0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2=0.81, p<0.0001). CONCLUSIONS: Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order to assess the possible clinical implications of chronic therapy with TAD.

Aged↗
PubMed2005

Cervical spondylotic myelopathy: 10 years of prospective outcome analysis of anterior decompression and fusion.

BACKGROUND: Fifty-one patients with cervical spondylotic myelopathy (CSM) treated by anterior cervical corpectomy with fusion (ACWF) at our institution were included in a study during a period of 10 years to evaluate neurological, anatomical, and functional outcomes including satisfaction levels. METHODS: We have completed a prospective evaluation of 39 patients with spondylotic myelopathy submitted to ACWF during the period of 1989-2000. The data were analyzed for age, duration of symptoms, severity of preoperative neurological deficit, and single-level or multilevel compressive status looking for possible association with prognostic surrogate data and clinical outcome that were evaluated with the Nurick score and a survey of level of satisfaction. RESULTS: Of the 51 patients, 39 fullfilled the intended follow-up being 28 men (71.8%) and 11 women (28.2%). The average age was 63.5 years. Duration of symptoms ranged from 1 to 240 months (mean, 38.1 months). The mean preoperative Nurick scale score was 2.97; the mean postoperative score was 2.1. The most frequently involved vertebral body was C5 (71.7%). The follow-up period was longer than 18 months for all patients. Postoperative nonneurological complications occurred in 8 patients (15.6%). The mortality rate was 1.9% (n = 1). Postoperative results showed improvement in 25 patients (64.1%), no change in 13 (33.3%), and worsening in 1 (2.6%). The correlation coefficient of preoperative and postoperative Nurick scores was 0.733 (R(2) = 0.53). Of the 39 patients, 31 answered the questionnaire for quality of life-19 (61.2%) were very satisfied, 6 were satisfied (19.35%), and 6 were not satisfied (19.35%). CONCLUSION: Most patients (80.6%) were very satisfied or satisfied with the outcome and would decide again for the surgery (87%) if the results were previously known. Anterior cervical corpectomy with fusion was a reliable and rewarding procedure for CSM, with functional improvement in most patients. Excellent long-term outcome results in cervical fusion can be achieved without the use of hardware instrumentation.

Adult↗
PubMed2005

Effects of testosterone on sexual function in men: results of a meta-analysis.

OBJECTIVES: The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta-analysis of placebo-controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed in MEDLINE, the Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, a total of 17 randomized placebo-controlled trials were found to be eligible. For each domain of sexual function we calculated the standardized mean difference relative to T and reported the results of pooled estimates of T treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross-over. The median study length was 3 months (range 1-36 months). Our meta-analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut-off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta-regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta-analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low-normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long-term safety data are not available. The present meta-analysis highlights the need, and pitfalls, for large-scale, long-term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle-aged and elderly men with reduced T levels and ED.

Adult↗
PubMed2004

Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa.

By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA and protein abundance was several fold higher in human male than in female reproductive tracts. The highest mRNA level (>1 x 10(7) molecules/microg total RNA) was detected in human corpora cavernosa (CC), where PDE5 protein was immunolocalized in both muscular and endothelial compartment. The possible role of androgens in regulating PDE5 expression was studied using a previously established rabbit model of hypogonadotropic hypogonadism. In this model, hypogonadism reduced, and testosterone (T) supplementation restored, CC PDE5 gene and protein expression. In addition, T supplementation completely rescued and even enhanced cyclic GMP conversion to metabolites, without changing IC(50) for sildenafil (IC(50) = 2.16 +/- 0.62 nm). In control CC strips, sildenafil dose-dependently increased relaxation induced by electrical field stimulation, with EC(50) = 3.42 +/- 1.7 nm. Hypogonadism reduced, and T increased, sildenafil effect on electrical field stimulation, again without changing their relative EC(50) values. CC sensitivity to the NO-donor NCX4040 was greater in hypogonadal rabbit strips than in control or T-treated counterparts. Moreover, sildenafil enhanced NCX4040 effect in eugonadal rabbit strips but not in hypogonadal ones. This suggests that androgens up-regulate PDE5 in rabbit penis. We also measured PDE5 gene expression and metabolic activity in human CC from male-to-female transsexual individuals, chronically treated with estrogens and cyproterone acetate. Comparing the observed values vs. eugonadal controls, PDE5 mRNA, protein, and functional activity were significantly reduced. In conclusion, we demonstrated, for the first time, that androgens positively regulate PDE5, thus providing a possible explanation about the highest abundance of this enzyme in male genital tract.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Hormonal supplementation and erectile dysfunction.

The role of testosterone on sexual desire is well established. However, the effects of low testosterone levels in the pathophysiology of erectile mechanism in humans remains unclear. Recent evidence indicate that approximately 10-20% of men with erectile dysfunction (ED) have hormonal abnormalities, raising up to 35% over the age of sixty. It is now clear that sexual desire and erectile function in humans are both responsive to androgens, probably at different threshold values. In fact, different degrees of testosterone deficiency may determine a sequence of molecular penile events leading to reduced capacity of penile smooth muscle and endothelial cells of relaxation, without greatly affecting sexual desire. Also, androgens may directly control the expression and activity of phosphodiesterase type-5 in human corpus cavernosum. In some selected men with total testosterone below 10-13nmol/l and/or free testosterone below 200-250pmol/l, androgen supplementation may improve therapeutic efficacy of phosphodiesterase type-5 inhibitors. For ageing men with partial androgen deficiency (PADAM) who fail first-line oral treatments in whom androgens are not contraindicated, a combination of testosterone and phosphodiesterase type-5 inhibitors may be considered to improve erectile function and improve the quality of life.

Androgens↗
PubMed2003

Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction.

OBJECTIVES: We have recently shown that, in men with erectile dysfunction (ED), free testosterone (FT) directly correlates with penile arterial inflow. This led us to further investigate the effect(s) of androgen administration on cavernous arteries in patients failing sildenafil treatment. DESIGN: Prospective randomized placebo-controlled pilot study. PATIENTS: Twenty patients with arteriogenic ED as evaluated by dynamic colour duplex ultrasound (D-CDU) studies, normal sexual desire but testosterone (T) and FT in the lower quartile of normal range (low-normal), not responding to sildenafil treatment (100 mg) on six consecutive attempts. MEASUREMENTS: All patients had D-CDU, hormonal [LH, prostate-specific antigen (PSA), total and free testosterone, sex hormone-binding protein (SHBG), oestradiol], biochemical [haematocrit, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides], and sexual evaluations [International Index of Erectile Function (IIEF)] before and after 1 month of therapy with transdermal testosterone (5 mg/day, n = 10) or placebo along with sildenafil treatment on demand. Measurement of flow parameters by D-CDU on cavernous arteries was the primary endpoint of the study. Improvement of erectile function was assessed using the IIEF questionnaire and the Global Assessment Question (GAQ). RESULTS: One month treatment with transdermal testosterone led to a significant increase in T and FT levels (23.7 +/- 3.3 SD vs. 12.8 +/- 2.1 nmol/l and 473 +/- 40.2 vs. 260 +/- 18.1 pmol/l, P < 0.01, respectively). In addition testosterone administration induced a significant increase in arterial inflow to cavernous arteries measured by D-CDU (32 +/- 3.6 vs. 25.2 +/- 4 cm/s, P < 0.05), with no adverse effects. Also, a significant improvement in erectile function domain score at IIEF was found in the androgen but not in the placebo-treated patients (21.8 +/- 2.1 vs. 14.4 +/- 1.4, P < 0.05) which was associated with significant changes in the GAQ score (80%vs. 10%, P < 0.01). CONCLUSIONS: In patients with arteriogenic ED and low-normal androgen levels, short-term testosterone administration increases T and FT levels and improves the erectile response to sildenafil likely by increasing arterial inflow to the penis during sexual stimulation.

Aged↗
PubMed2002

Penile pharmacotesting in diagnosing male erectile dysfunction: evidence for lack of accuracy and specificity.

Penile pharmacotesting (PPT) with alprostadil (PGE1) represents the most common diagnostic approach to male erectile dysfunction (ED). A positive response - i.e. normal erectile rigidity of sustained duration - is presumed to exclude venous or arterial pathology with enough accuracy. To test this assumption we compared PPT vs. flowmetric results obtained by colour-duplex Doppler ultrasound (CDDU) in patients (pts) undergoing diagnostic evaluation for ED under conditions of maximal cavernous relaxation. A total of 195 non-consecutive impotent pts were diagnosed after dynamic CDDU as non-vasculogenic (NOR), or having arteriogenic (AR), veno-occlusive (VO) or mixed (MX) ED. Maximal erection obtained after PPT was scored as: type-1 (full tumescence - no sustained rigidity, angle on the abdominal plane >90 degrees), type-2 (sustained partial erection, valid for intromission, angle=90 degrees) and type-3 (sustained full erection, angle <90 degrees). Comparing PPT with flowmetric results, we found that a type-3 response had 20% false negative diagnosis of NOR (17% of AR- and 3% of VO- and MX-ED, respectively), while a type-2 response had 63% false negative diagnosis (20% of AR, 37% of VO- and 6% MX-ED, respectively). Type-1 response was associated with the presence of VO dysfunction in 99% of cases. These data suggest that a positive response to PPT (type-2 and type-3) assessed by the visual rating of erection is associated with both arterial (up to 20%) and/or VO (up to 43%) ED, as detected by CDDU. We conclude that PPT alone is a misleading diagnostic test to exclude vascular ED and that dynamic CDDU should be offered to pts investigated for male ED.

Adult↗