Impact of diabetes on male sexual function in streptozotocin-induced diabetic rats: Protective role of soluble epoxide hydrolase inhibitor.

Diabetes-induced male sexual dysfunction is associated with endothelial dysfunction. Inhibition of soluble epoxide hydrolase (sEH) is known to improve endothelial function in diabetes. Therefore, we hypothesized that sEH inhibitor (sEHI), [trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid] / t-TUCB can restore the male sexual function in diabetic rat. After one week of administration of diabetogenic agent STZ (52 mg/kg i.p) injection, diabetic rats were treated with t-TUCB (0.1 and 0.3 mg/kg, p.o) or vehicle for 8 weeks. The sexual behaviour parameters of the animals were evaluated at the end of dosing period. The levels of testosterone and glucose in serum, and sperm were quantified. Effect of treatment on weight of reproductive organs and histopathology of penile tissue was evaluated. Diabetes had a negative effect on male sexual function, weight of sexual organs and production of sperm with a parallel decrease in the level of testosterone. The sEHI, t-TUCB, significantly preserved the sexual function and minimized an increase in the level of blood glucose in diabetic rats. It also prevented a decrease in the level of testosterone and sperm in diabetic rats, in comparison to diabetic control rats. Further, diabetes induced distortion of corpus cavernosum was attenuated by t-TUCB. Based on our findings, sEHI may delay the development of sexual dysfunction in diabetes.

Expressions of vaginal endothelial nitric oxide synthase and phosphodiesterase 5 in female sexual dysfunction: a pilot study.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the expression of endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE) 5 in vaginal tissue of premenopausal women experiencing stress urinary incontinence (SUI) with and without sexual dysfunction. METHODS: Women presenting for treatment of SUI were screened using the Female Sexual Function Index (FSFI) and 10 were selected who met the criteria for female sexual dysfunction (FSD) and 10 asymptomatic controls. Vaginal tissue specimens were obtained from those premenopausal women aged ≥40 years who had had sexual activity ≥2 times every month for the last 6 months and who were scheduled to undergo surgery for SUI. FSD criteria was FSFI scores <18 and arousal domain scores <3. The control group had FSFI scores ≥26 and individual domain scores ≥4. The expressions of eNOS and PDE 5 were compared in the two groups using immunofluorescence staining and western blotting. RESULTS: The mean total FSFI scores were 30.4 ± 2.6 and 15.3 ± 2.3 in the control and FSD groups respectively. In immunofluorescence staining, eNOS and PDE5 were localized in the vaginal epithelium. In western blotting, the expressions of eNOS and PDE5 were significantly lower in the FSD group than in the control group (p = 0.003 and p = 0.038 respectively). CONCLUSIONS: eNOS and PDE5 in the vagina may play important roles in the pathophysiology of FSD.

Comorbidity in patients with Dhat syndrome: a nationwide multicentric study.

INTRODUCTION: There are limited numbers of studies on Dhat syndrome. Major limitations of the existing literature are heterogeneous assessment methods used to describe the comorbidity and small sample size from isolated centers. AIM: To assess comorbidity with a common methodology in patients with Dhat syndrome from multiple centers across India. METHODS: Using a cross-sectional design, this multicentric study involved assessment of 780 male patients, aged more than 16 years, across 15 study centers. MAIN OUTCOME MEASURES: ICD-10 criteria (for evaluation of psychiatric morbidity and sexual dysfunction) RESULTS: About one-third (32.8%) of the cases had no comorbidity. One-fifth (20.5%) of the patients had comorbid depressive disorders and another one-fifth (20.5%) had comorbid neurotic, stress-related and somatoform disorders. Half (51.3%) of the study sample had comorbid sexual dysfunction. When various combinations of comorbidities were evaluated, it was seen that more than one-fourth (28.7%) of the patients had only comorbid sexual dysfunction and one-sixth (15.9%) had only comorbid depressive/anxiety disorders. A little more than one-fifth (22.6%) had comorbidity of both sexual dysfunction and depressive/anxiety disorders. CONCLUSION: Comorbid sexual dysfunction is seen in half of the cases of Dhat syndrome, and it is more common than comorbid depressive and anxiety disorders.

Does post-caesarean dyspareunia reflect sexual malfunction, pelvic floor and perineal dysfunction?

The aim was to define post-caesarean dyspareunia as a sexual and pelvic-perineal symptom. Post-caesarean (80 elective, 104 emergency) and 100 vaginally delivered primiparae had domiciliary interviews at 10 months postpartum. A total of 50 (28% and 27%) post-caesarean and 46 (46%) vaginally delivered, reported dyspareunia. Severely impaired general sexual health occurred in 82 (24% elective, 25% emergency, 35% vaginally delivered) as category 3 (dyspareunia with sexual symptoms) and 27 (10% elective, 7% emergency, 12% vaginally delivered) as category 4 (reduced frequency < 6). The risk of dyspareunia (RR 1.14, CI 0.73, 1.77) or impaired general sexual health (RR 0.93, CI 0.32, 2.74) was similar among those with or without perineal trauma. Both caesarean and perineal scars were associated with sexual malfunction. Primiparae with new incontinence had a lower risk of dyspareunia than impaired general sexual health. Awareness of the associations of post-caesarean dyspareunia and impaired general sexual health with incontinence would facilitate appropriate obstetric decision-making. Further research is indicated.

Treatment options for sexual dysfunction in patients with chronic kidney disease: a systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model. RESULTS: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI -2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy. CONCLUSIONS: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.

Sildenafil citrate for female sexual arousal disorder: a future possibility?

Female sexual arousal disorder (FSAD) is a common disorder encountered in clinical practice, with self-reported arousal difficulties reported in up to 26% of American women. Various oral therapies for FSAD have been studied, including sildenafil citrate, a phosphodiesterase inhibitor that is currently used to treat male erectile dysfunction. In vitro studies of sildenafil citrate have demonstrated smooth-muscle relaxation in clitoral tissue, and phosphodiesterase type-5 has been shown to be present in vaginal, clitoral and labial smooth muscle; these findings have led to theories that sildenafil citrate might be successful for treating FSAD. This Review discusses the data from clinical trials that have assessed sildenafil citrate for the treatment of FSAD; the trials show that sildenafil citrate is moderately effective. Sildenafil citrate may also be effective in women with FSAD secondary to multiple sclerosis, diabetes or antidepressant use; however, more trials in these patient populations are required to confirm these findings.

Validated questionnaires for assessing sexual dysfunction and BPH/LUTS: solidifying the common pathophysiologic link.

Erectile dysfunction (ED) and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) share many epidemiologic and clinical similarities. First-line therapy for both conditions include oral medications (alpha blockers, phosphodiesterase inhibitors). The impetus to develop and use questionnaires to characterize these two conditions is based on the trend away from invasive diagnostic testing to the use of patient-reported outcomes or validated self-administered questionnaires. The International Prostate Symptom Score, the International Index of Erectile Function, the Male Sexual Health Questionnaire (MSHQ) and the MSHQ short form are similar patient-reported assessment questionnaires used for research or clinical evaluation of BPH/LUTS, ED and ejaculatory dysfunction. These patient-based self-administered questionnaires are likely to assume an ever increasing important role in the future, as oral BPH therapies are considered for the treatment of ED and oral ED therapies are considered for the treatment of BPH/LUTS.

The role of phosphodiesterase type 5 inhibitors in the management of premature ejaculation: a critical analysis of basic science and clinical data.

OBJECTIVES: To assess the usefulness of the phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of premature ejaculation (PE) and to describe possible mechanisms to explain their effect. METHODS: A MedLine search was performed for peer-reviewed articles on the role of PDE5-Is in managing PE. No meta-analysis method was used. RESULTS: Five manuscripts that examined the efficacy of PDE5-Is in the treatment of PE were retrieved. Three studies used sildenafil as monotherapy and two used it in combination with a serotonin selective reuptake inhibitor (SSRI). Three studies demonstrated a beneficial effect of sildenafil in the treatment of PE, as measured by intravaginal ejaculatory latency time (IELT) and by different questionnaires assessing the patients' subjective feelings of ejaculatory control, sexual satisfaction, and anxiety. One study showed the superiority of sildenafil compared to other modalities. Two studies showed that combination therapy of paroxetine and sildenafil was better than paroxetine alone. One study did not demonstrate a beneficial effect of sildenafil in prolonging IELT, but showed that sildenafil improved patients' perception of ejaculatory control. Another study showed that topical anesthetics were better than sildenafil in the treatment of PE but did not use IELT or a validated questionnaire to measure the efficacy of treatment. Several possible mechanisms could explain effectiveness of the PDE5-Is for treatment of PE: centrally, through the effect on the nitric oxide/cyclic guanosine monophosphate pathway; peripherally by causing relaxation of smooth muscle in the vas deferens, seminal vesicles, prostate, and urethra and inhibition of adrenergic transmission; or locally by inducing peripheral analgesia. Another possibility might be prolongation of the duration of erection. CONCLUSIONS: Encouraging evidence supports the role of PDE5-Is for treating PE. Possible therapeutic mechanisms of action of PDE5-Is are multiple and complex and include central and peripheral effects. A large population, multicenter, randomized, double-blind, placebo-controlled study is needed to elucidate the efficacy of PDE5-Is in the treatment of PE.

Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review.

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.

RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic insights.

Penile erection is a complicated event involving the regulation of corpus cavernosal smooth muscle tone. Recently, the small monomeric G-protein RhoA and its downstream effector Rho-kinase have been proposed to be important players for mediating vasoconstriction in the penis. RhoA/Rho-kinase increases MLC (myosin light chain) phosphorylation through inhibition of MLCP (MLC phosphatase) thereby increasing Ca2+ sensitivity. This review will outline the RhoA/Rho-kinase signalling pathway, including the upstream regulators, guanine nucleotide exchange factors, GDP dissociation inhibitors and GTPase-activating proteins. We also summarize the current knowledge about the physiological roles of RhoA/Rho-kinase in both male and female erectile tissues and its aberrations contributing to erectile dysfunction in several disease states. Understanding the RhoA/Rho-kinase signalling pathway in the regulation of erection is important for the development of therapeutic interventions for erectile dysfunction.

Does increased aromatase activity in adipose fibroblasts cause low sexual desire in patients with HIV lipodystrophy?

There is evidence from our own unit and other workers that many patients who have lipodystrophy on HAART given for HIV disease also have raised oestrogen levels and complain of low sexual desire. This hypothesis paper discusses a possible pathological mechanism for these changes--an increase in the number of fibroblasts and macrophages present in lipoatrophic areas that could convert testosterone to oestrogen by intracellular aromatisation. This process is known to be enhanced by increased levels of tumour necrosis factor, interleukin 6 (IL-6), and hydroxycorticosteroids present in many patients with HIV lipodystrophy. Treatment options are discussed, including aromatase inhibitors and testosterone.

[Luteotropic hormone (LTH) level in men with alcoholism]. / Nivo na luteotropniia khormon (LTKh) pri muzhe, bolni ot alkokholna bolest.

The authors examined 46 male patients with alcoholic disease and 10 healthy ones, aged from 20 to 50. The LTH dosing is performed by radioimmunologic method with double antibodies. A significant LTH decrease was found in the alcoholic male patients, as compared with the healthy control ones, convincingly speaking of the LTH affection in chronic alcoholism. The absence of discrepancy in LTH level in patients with and without sexual disorders gave grounds to the authors to persume that that hormone has not a definite participation in the sexual disturbances origination in alcoholism.