Surveillance of Indonesian female sexual function after hysterectomy.

BACKGROUND: Sexual function is one component of quality of life that could be fulfilled by humans. Hysterectomy, which is an operative procedure in women, may cause disturbance in sexual function. AIM: This study aims to determine the surveillance of sexual function after hysterectomy. METHODS: This is a cross-sectional study involving 92 gynecological tumor patients who had undergone a hysterectomy by open laparotomy procedure for at least 3 months. Evaluation of sexual dysfunction using the female sexual function index (FSFI-6) questionnaire, which assesses sexual function in the form of sexual disorder, sexual dysfunction, desire disorders, stimulation, orgasm disorders, and pain. The study was conducted in September-November 2018 in Dr. Cipto Mangunkusumo Hospital, Jakarta. The patients were divided into total and radical hysterectomy groups and whether castration was performed. RESULTS: The total group had 71 total hysterectomy and 21 radical hysterectomy patients. Sexual dysfunction (radical hysterectomy 47.6%, n = 10/21; total hysterectomy 28.2%, n = 20/71; castration 33.8%, n = 24/71; and without castration 28.6%, n = 6/21); orgasmic disorders (total hysterectomy 28.2%, n = 20/71; radical hysterectomy 47.6%, n = 10/21; castration 33.8%, n = 24/71; without castration 28.6%, n = 6/21); and pain disorder (radical hysterectomy 28.6%, n = 6/21; compared with 9.9%, n = 7/71 total hysterectomy). CONCLUSION: No significant differences were found between sexual function after radical hysterectomy and total hysterectomy, as well as between the castration groups. Based on these findings, sexual function is an important reference for health professionals to be considered in conducting counseling before and after surgery.

Fibrotic Diseases of the Human Urinary and Genital Tract: Current Understanding and Potential Strategies for Treatment.

Fibrosis is a disease condition characterized by abnormalities of the extracellular matrix, such as accumulation of the transforming growth factor ß, infiltration by myofibroblasts, deposition of collagen, and a generalized dysregulation of collagen maturation. It can severely impair the function of organs by replacing normal tissue with a highly collagenized matrix, thereby reducing the elasticity and compliance of tissues. Fibrotic diseases of the genitourinary tract present relevant problems in healthcare, and their principles of pathophysiology remain unclarified; hence, the armamentarium for prevention and treatment is limited. These diseases include renal fibrosis, Peyronie's disease and ureteral and urethral strictures due to perturbations in the process of wound healing in response to injuries. Such deteriorations may contribute to obstructive uropathies or sexual dysfunction. This review provides a brief overview of the most frequent fibrotic diseases of the genitourinary system and of how the pathophysiology is related to symptoms, and also highlights potential therapeutic strategies to address the abnormal deposition of collagen. Although the understanding of factors associated with fibrotic conditions of the urinary and genital tract is still limited, some beneficial advances have been made. Further research will serve to provide a more comprehensive insight into factors responsible for the development of fibrotic tissue deposition.

Is cortisol an endogenous mediator of erectile dysfunction in the adult male?

Background: It has been speculated for decades whether there is a significance of the adrenal corticosteroid cortisol in the process of male sexual function, including the control of sexual arousal and penile erection. In order to investigate further the role of the adrenocorticotropic axis in the physiological process of penile erection, we aimed to determine the course of cortisol in the cavernous and systemic blood through different stages of sexual arousal in patients suffering from erectile dysfunction (ED) in comparison to a cohort of healthy males. Methods: Fifty-four healthy adult males and 45 patients with ED were presented sexually explicit visual material in order to elicit tumescence and (in the healthy males) rigid erection. Blood was collected from the cavernous space (corpus cavernosum penis, CC) and a cubital vein (CV) at different stages of the sexual arousal cycle as indicated by the penile stages flaccidity, tumescence, rigidity (attained only by the healthy males) and detumescence. Cortisol (µg/dL serum) was measured using a radioimmunometric assay (RIA). Results: In healthy males, cortisol decreased in both the cavernous and systemic blood with the beginning of sexual stimulation (CV: 15 to 13, CC: 16 to 13). At detumescence, in the systemic circulation, no alterations in cortisol levels were registered, whereas it decreased further in the CC (to 12). In the ED patients, no significant changes in cortisol were noticed in the systemic and cavernous blood. Conclusions: The findings indicate that cortisol might act as an antagonist of the normal sexual response cycle of the adult male. A dysregulation of the secretion and/or degradation of the hormone might well play a role in the manifestation of ED.

Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human seminal vesicles.

Background and Aims: The transient receptor potential cationic channel ankyrin 1 (TRPA1), a channel protein permeable to most divalent cations, has been suggested to play a role in mechano-afferent/efferent signaling (including the release of neurotransmitters) in the human urinary tract (bladder, prostate, and urethra). To date, only a few studies have addressed the expression of this receptor in male and female reproductive tissues. The present study aimed to evaluate human seminal vesicles (SVs)  for the expression and localization of TRPA1. Methods: SV tissue was obtained from 5 males who had undergone pelvic surgery due to malignancies of the prostate or urinary bladder. The expression of messenger ribonucleic acid (mRNA) specifically encoding for the TRPA1 protein was elucidated by means of reverse transcriptase polymerase chain reaction (RT-PCR). Using immunohistochemical methods, the distribution of TRPA1 was examined in relation to the endothelial and neuronal nitric oxide synthases (eNOS, nNOS) and the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). Results: RT-PCR revealed signals related to the expected molecular size of 656 bp. Immunohistochemistry demonstrated that TRPA1 is located in nerves running through the smooth muscle portion of the SV. Here, the protein is in part co-localized with nNOS and CGRP, whereas no co-localization with VIP was registered. Dot-like signals specific for TRPA1 were observed in the cytoplasm of epithelial cells lining the lumen of glandular spaces. The epithelial layer also presented staining for eNOS. The smooth musculature appeared free of immunosignals for TRPA1. Conclusion: The results convincingly show the expression of TRPA1 in nerve endings as well as in epithelial cells of the SV. Based on its location in epithelial cells, TRPA1 might be involved in the mechanism of the NO/cyclic guanosine monophosphate (GMP)-mediated signaling and also the control of secretory function (mediated by cyclic GMP) in the human SV.

Expression of Phosphodiesterase (PDE) Isoenzymes in the Human Male and Female Urethra.

PURPOSE: Although it has been supposed that the NO/cyclic GMP system produces inhibitory signals to reduce the resistance of the bladder outlet and urethra during the micturition phase, little is known on the mechanisms controlling the function of urethral smooth muscle. The aim of the present study was to examine in the male and female urethra the expression of phosphodiesterase (PDE) isoenzymes, known as key proteins of the cyclic GMP/AMP signaling. METHODS: Urethral tissue was obtained from 4 female cadavers and 7 male patients (who had undergone gender reassignment surgery). The expression of mRNA encoding for PDE1A, 1B, 1C, 2A, 4B, 4D, 5A, 10A and 11A was investigated by means of real-time polymerase chain reaction. Western blot (WB) analysis was conducted to detect PDE isoenzymes. RESULTS: RT-PCR revealed relevant amounts of mRNA encoding for PDE1A, 2A, 4B, 5A, 10A and 11A in male and female urethral tissue. The expression of PDE1A, 2A, 4B and 10A was 2-fold higher in the female than in the male urethra, whereas the expression of PDE11A mRNA was 7-fold higher in the male tissue. In the WB experiments, immunosignals specific for PDE1A, PDE4A and 4B and PDE11A were of higher degree in the female than the male tissue specimens, while an almost equivocal expression of PDE2A, PDE5A and PDE10A was registered. CONCLUSION: On the level of mRNA and function proteins, different patterns of expression of PDE isoenzymes were registered in human male and female urethra. Future studies may clarify whether inhibition of PDE isoenzymes is likely to facilitate the relaxation of the outflow region in both sexes.

Arginase enzymes in the human prostate: A molecular biological and immunohistochemical approach.

The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. This study investigated the expression of arginase type I and II in the human prostate. Nondiseased prostate tissue was obtained during pelvic surgeries (prostatectomy, cystoprostatectomy). Tissue sections were exposed to antibodies directed against Arg I and II, cGMP, the phosphodiesterase 5 and nNOS. The expression of mRNA transcripts encoding for Arg I and Arg II was investigated using molecular biology. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of mRNA encoding for Arg I and II, immunofluorescence specific for Arg I was seen in the stromal smooth musculature, and labelling for PDE5 and cyclic GMP was also observed. Nerve fibres containing nNOS were identified running across the smooth musculature. Immunostainings for Arg II did not yield signals. These findings are in support of the notion that, in the prostate, Arg is involved in the modulation of the activity of the NO system.

Course of transforming growth factor ß1 in the systemic and cavernous blood of healthy males through different penile conditions.

Studies on erectile dysfunction (ED) have revealed a relationship between smooth muscle atrophy and the accumulation of collagen in the corpus cavernosum (CC). Transforming growth factor ß1 (TGF ß1) is a cytokine which has been proposed to be involved in the fibrotic process in the CC. We aimed to evaluate the course of TGF ß1 in the systemic and cavernous blood of 17 healthy males through different phases of the sexual arousal response (exemplified by the penile conditions flaccidity, tumescence, rigidity and detumescence). An enzyme-linked immunoassay was used to measure the concentration of TGF ß1 (ng/ml) in both the systemic and cavernous blood at the stages of flaccidity, tumescence and detumescence. TGF levels were significantly higher in the cavernous compartment than in the systemic blood. A linear decrease was evident in the cavernous blood when the flaccid penis became tumescent (24.3 ± 14.5 to 13.9 ± 6.5) and rigid (to 8.7 ± 3.1). At detumescence, TGF increased to 18.3 ± 10.4. In contrast, the levels in the systemic circulation remained unchanged. The results are in support of the hypothesis that the concentration of TGF ß1 in the CC is regulated by adequate blood flow and oxygenation.

The Effectiveness of a Three Day Course Antibiotic Post-urodynamic Study in Preventing Lower Urinary Tract Infection.

AIM: to evaluate the effect of a 3-day course antibiotic post-urodynamic study (UDS) to prevent urinary tract infection (UTI). METHODS: this was a randomized double blind clinical trial on the proportion of UTI in patients who received levofloxacin 500 mg once a day for 3 days after UDS compared to nontreated patients. The outcome of this study was the incidence of lower UTI in levofloxacin group and placebo group. Lower UTI was defined as patient with one or more clinical symptoms of lower UTI and one or more urinalysis parameter of UTI. Chi-square was used to evaluate the association between the lower UTI and treatment group. RESULTS: a total of 126 patients were enrolled in this study from two outpatient urology clinics in Jakarta: Cipto Mangunkusumo Hospital and Asri Hospital. Overall, 26 patients (20.6%) had UTI post UDS (8 out of 63 patients from levofloxacin arm (12.7%) and 18 out of 63 patients from placebo arm (28.6%); p=0.028). The most common isolate found was E. coli (n=18 patients; 69.2%). The most common indications to perform UDS were Lower Urinary Tract Symptoms (LUTS) with failure of therapy (n=43 patients; 25%), LUTS after invasive treatment (n=29 patients; 16.9%), and overactive bladder with failure of therapy (n=22 patients; 12.7%). CONCLUSION: the use of antibiotic post-UDS can prevent incidence of lower UTI.

Effectiveness of Short Term Percutaneous Tibial Nerve Stimulation for Non-neurogenic Overactive Bladder Syndrome in Adults: A Meta-analysis.

AIM: to evaluate the effectiveness of short-term PTNS for non-neurogenic OAB in adults systematically by comparing with sham procedure and other treatments. METHODS: we performed a systematic review of cohort study. Data sources were MEDLINE, EMBASE, CINAHL, National Library for Health, Cochrane, and google scholar from 2005 through 2015. Meta-analysis was performed using the random effects model. Heterogeneity of effects was assessed by calculating I2 statistic. Statistical analysis was performed using Review Manager 5.3 for RCT meta-analysis. RESULTS: we analized 11 randomised controlled trial (RCT) and five prospective non-comparative studies with variable success rate. Based on percentage of responders, the results were 37.3% - 81.8% in PTNS group, 0% - 20.9% in sham group, 54.8% in anti-muscarinic group, and 89.7% in multimodal group. The decrease of voiding symptoms episodes per day was found in PTNS (0.7-4.5), sham (0.3-1.5), and anti-muscarinic (0.6-2.9) groups. In meta-analysis of four RCTs, the results favour PTNS over sham procedure with overall risk ratio of 7.32 (95% CI of 1.69-32.16), p=0.09, I2=54%. CONCLUSION: there is an evidence of effectiveness of short term PTNS in treatment of non-neurogenic OAB. PTNS is proven significantly better than sham procedure.

Prevalence of urinary incontinence, risk factors and its impact: multivariate analysis from Indonesian nationwide survey.

AIM: to describe the profile of urinary infection (UI) and to analyze its risk factors and impacts. METHODS: subjects were enrolled consecutively from pediatric, urology, obstetrics and gynecology, and geriatric outpatient clinics at six teaching hospitals in various regions of Indonesia. Those with urinary tract infection and diabetes mellitus were excluded. The UI questionnaire was adapted from the 3 Incontinence Questions (3IQ). Written informed consent was obtained prior to the interview. RESULTS: about 2765 completed questionnaires were obtained. The overall UI prevalence was 13.0%, which consisted of prevalence of stress UI (4.0%), urgency UI/wet OAB (4.1%), dry OAB (1.6%), mixed UI (1.6%), overflow UI (0.4%), enuresis (0.4%), other UI (0.7%). The prevalence of UI was significantly higher (p<0.001) in geriatric population (22.2%) compared to the adult (12.0%), and pediatric population (6.8%). There was no prevalence difference (p>0.05) between male and female subjects. Enuresis and urgency UI/wet OAB were the most common UI in pediatric population. The prevalence was 2.3% and 2.1% respectively. Urgency UI and stress UI were the two most common type in adult and geriatric population. Both have an equal prevalence of 4.6%. The multivariate analysis showed that the prevalence of UI increased with LUTS (PR 4.22, 95%CI 2.98-5.97), chronic cough (PR 2.08, 95% CI 1.32-3.28), and fecal incontinence (PR 1.85, 95% CI 1.03-3.32). We found that UI impaired family life (25.3%), sexual relationship (13.6%), and job/school performance (23.7%). Frequent toilet use and reducing fluid intake were the two most common behavior changes. CONCLUSION: the prevalence of UI in Indonesia is nearly similar to other Asian countries. It increases with age and is not affected by gender. LUTS, chronic cough, and fecal incontinence may have significant effects on the prevalence. UI seems to impact daily life and behavior.

Effects of endopeptidase inhibition on the contraction-relaxation response of isolated human vaginal tissue.

INTRODUCTION.: Vasoactive peptides, such as bradykinin, C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP), and endothelin 1 (ET-1), are assumed to be involved in the control of female genital vascular and nonvascular smooth muscle. Tissue levels of said peptides are controlled by the activity of endopeptidase enzymes. Theoretically, in female genital tissues, inhibiting the degradation of bradykinin, CNP, and VIP, or the conversion of Big ET-1 into ET-1 should result in an enhancement in smooth muscle relaxation and, thus, an improvement in sexual response. AIM.: Elucidate the effects of the endopeptidase inhibitor KC 12615 on the contraction/relaxation response of isolated human vaginal smooth muscle to Big ET-1, bradykinin, CNP, or VIP. METHODS.: Tissue bath experiments were carried out to ascertain the responses of human vaginal tissue challenged by ET-1 (0.1 µM) to increasing concentrations of bradykinin, CNP, and VIP (0.01 µM, 0.1 µM, and 1 µM, respectively). The effects were also evaluated following preexposure to KC 12615 (10 µM, for 20 minutes). MAIN OUTCOME MEASURES.: Measure the effects of KC 12615 on the relaxation of isolated human vaginal smooth muscle brought about by bradykinin, CNP, or VIP and the contraction mediated by Big ET-1. RESULTS.: The tension induced by ET-1 was reversed by bradykinin, CNP, or VIP (-25 ± 6.6%, -13.3 ± 2.2%, and -17.6 ± 10%, respectively). Big ET-1 induced contraction of the vaginal tissue. Preexposure of the tissue to KC 12615 increased the relaxation exerted by bradykinin, CNP, or VIP (to -39.2 ± 5.8%, -40.7 ± 7.3%, and -44.6 ± 19%, respectively). The contraction induced by Big ET-1 was attenuated in the presence of KC 12615 (to approximately 25% of the initial response). CONCLUSION.: Inhibition of endopeptidase activity can antagonize the contraction of human vaginal tissue induced by Big ET-1 and increase the relaxation induced by vasoactive endogenous peptides.

Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study.

INTRODUCTION: Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. AIMS: To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. METHODS: The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 µM) on the tension induced by 0.1 µM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 µM, 0.1 µM, 1 µM) and the production of cAMP and cGMP determined by means of radioimmunoassays. MAIN OUTCOME MEASURES: Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RESULTS: RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively. CONCLUSION: Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.