Diagnosis and Treatment of Erectile Dysfunction for Reduction of Cardiovascular Risk

PURPOSE: We established erectile dysfunction as an often neglected but valuable marker of cardiovascular risk, particularly in younger men and men with diabetes. We also reviewed evidence that lifestyle change, combined with informed prescribing of pharmacotherapies used to mitigate cardiovascular risk, can improve overall vascular health and sexual functioning in men with erectile dysfunction.

MATERIALS AND METHODS: We performed a PubMed® search for articles and guidelines pertinent to relationships between erectile dysfunction and cardiovascular disease, cardiovascular and all cause mortality, and pharmacotherapies for dyslipidemia and hypertension. The clinical guidance presented incorporates the current literature and the expertise of the multispecialty investigator group.

RESULTS: Numerous cardiovascular risk assessment tools exist but risk stratification remains challenging, particularly in patients at low or intermediate short-term risk. Erectile dysfunction has a predictive value for cardiovascular events that is comparable to or better than that of traditional risk factors. Interventional studies support lifestyle changes as a means of improving overall vascular health as well as sexual functioning. Statins, diuretics, β-blockers and renin-angiotensin system modifiers may positively or negatively affect erectile function. Furthermore, the phosphodiesterase type 5 inhibitors used to treat erectile dysfunction may have systemic vascular benefits.

CONCLUSIONS: Erectile dysfunction treatment should be considered secondary to decreasing cardiovascular risk. However, informed prescribing may prevent worsening sexual function in men receiving pharmacotherapy for dyslipidemia and hypertension. As the first point of medical contact for men with erectile dysfunction symptoms, the primary care physician or urologist has a unique opportunity to identify those who require early intervention to prevent cardiovascular disease.

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology

BACKGROUND: Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking.

OBJECTIVE: Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model.

DESIGN, SETTING, AND PARTICIPANTS: Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test.

RESULTS AND LIMITATIONS: Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data.

CONCLUSIONS: This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology.

Urinary and Sexual Disorders After Laparoscopic TME for Rectal Cancer in Males

BACKGROUND: Urinary and sexual dysfunctions are frequent after surgery for rectal cancer. Total mesorectal excision (TME) improves local recurrence and survival rates, and does not hamper recognition and sparing of hypogastric and pelvic splanchnic nerves. It is not known how laparoscopic rectal resection could change functional complication rates.

MATERIALS AND METHODS: From a global series of 1,216 laparoscopic interventions for colorectal diseases, 35 cases of males less than 70 years old, undergoing rectal resection and TME for a T1-3M0 medium and low rectal cancer were selected. Urinary and sexual functions after the operations were retrospectively recorded by means of specific tools (International Prostate Symptom Score (IPSS) and IIEF questionnaires, respectively).

RESULTS: None of the patients necessitated permanent or intermittent catheterization. More than half the patients had no complaints about urinary functions; about one third had nocturia; 72% of the patients had an IPSS less that 10, and no case of IPSS worse that 31 was recorded. Sexual desire was reduced and spontaneous erectile function was impaired in almost half the cases, while induced erections were possible in about 90% of cases; about 70% of patients still had the possibility of penetration and a normal ejaculation and orgasm after the intervention.

DISCUSSION AND CONCLUSIONS: The present series confirms previous data and contribute to the creation of a benchmark specifically related to the laparoscopic approach to which surgeons should face when informing the patients before the operation. While severe urinary dysfunction is rare, sexual impairment remains a serious concern after rectal resection with TME.

The International Index of Erectile Function (IIEF):  a state-of-the-science review

The International Index of Erectile Function (IIEF): a state-of-the-science review

The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the clinical trial program for sildenafil, and has since been adopted as the ‘gold standard’ measure for efficacy assessment in clinical trials of ED. It has been linguistically validated in 32 languages and used as a primary endpoint in more than 50 clinical trials. This review summarizes early stages in the psychometric validation of the instrument, its subsequent adoption in randomized clinical trials with sildenafil and other ED therapies, and its use in classifying ED severity and prevalence. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. It has demonstrated consistent and robust treatment responsiveness in studies in USA, Europe and Asia, as well as in a wide range of etiological subgroups. Although only one direct comparator trial has been performed to date, the IIEF is also sensitive to therapeutic effects with treatment agents other than sildenafil. A severity classification for ED has recently been developed, in addition to a brief screening version of the instrument. This review includes the strengths as well as limitations of the IIEF, along with some potential areas for future research.

Male sexual dysfunction after rectal cancer surgery

PURPOSE: The aims of the study were to determine the extent of male sexual dysfunction after surgical treatment of rectal cancer and to examine the outcome of postoperative treatment with sildenafil.

METHODS: A prospective study was performed in patients who underwent attempted curative total mesorectal excision (TME) for low rectal cancers. Sexual function scores were determined by questionnaire preoperatively and at 3 and 12 months postoperatively. Outcomes were examined in patients who were sexually active preoperatively.

RESULTS: From 2000 to 2007, 207 patients underwent TME at our institution, of whom 49 (24%) were sexually active preoperatively. Erectile dysfunction and ejaculatory problems were present in 80% and 82%, respectively of the 49 patients at 3 months postoperatively, and in 76% and 67%, respectively at 12 months. Lateral lymph node dissection was a strong risk factor for postoperative sexual dysfunction. The impotency rate was 37% and 47% of patients were unable to ejaculate. Sildenafil was administered to 16 patients who requested the drug during follow-up, and sexual dysfunction was improved in 11 of these patients (69%).

CONCLUSION: Sexual dysfunction occurs frequently after rectal cancer treatment and is mainly caused by surgical damage in lateral lymph node dissection. Sildenafil may be effective for the treatment of sexual dysfunction.

Risk factors for sexual dysfunction after rectal cancer treatment

This study aimed to identify risk factors for long-term sexual dysfunction (SD) after rectal cancer treatment. Patients with resectable rectal cancer were randomised to total mesorectal excision with or without preoperative radiotherapy (PRT). Preoperatively and at 3, 6, 12, 18 and 24 months postoperatively, SD scores were filled out in questionnaires. Possible risk factors for postoperative deterioration of sexual functioning, including patients’ demographics, tumour-specific factors and treatment-related variables, were investigated with univariate and multivariable regression analyses. Increase in general SD, erectile dysfunction and ejaculatory problems were reported by 76.4, 79.8 and 72.2 percent of the male patients, respectively. Risk factors were nerve damage, blood loss, anastomotic leakage, PRT and the presence of a stoma. In female patients, increase in general SD, dyspareunia and vaginal dryness were reported by 61.5, 59.1 and 56.6 percent, respectively. This was associated with PRT and the presence of a stoma. SD occurs frequently after rectal cancer treatment and is caused by surgical (nerve) damage with an additional effect of PRT. Patients should be informed preoperatively, and education of surgeons in neuroanatomy may provide the key to the improvement of functional outcome.