Association between exposure to multiple metals and stress urinary incontinence in women: a mixture approach.

There is limited evidence linking exposure to heavy metals, especially mixed metals, to stress urinary incontinence (SUI). This study aimed to explore the relationship between multiple metals exposure and SUI in women. The data were derived from the National Health and Nutrition Examination Survey (NHANES), 2007-2020. In the study, a total of 13 metals were analyzed in blood and urine. In addition, 5155 adult women were included, of whom 2123 (41.2%) suffered from SUI. The logistic regression model and restricted cubic spline (RCS) were conducted to assess the association of single metal exposure with SUI risk. The Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) were used to estimate the combined effect of multiple metals exposure on SUI. First, we observed that blood Pb, Hg and urinary Pb, Cd were positively related to SUI risk, whereas urinary W was inversely related by multivariate logistic regression (all p-FDR < 0.05). Additionally, a significant non-linear relationship between blood Hg and SUI risk was observed by RCS analysis. In the co-exposure models, WQS model showed that exposure to metal mixtures in blood [OR (95%CI) = 1.18 (1.06, 1.31)] and urine [OR (95%CI) = 1.18 (1.03, 1.34)] was positively associated with SUI risk, which was consistent with the results of BKMR model. A potential interaction was identified between Hg and Cd in urine. Hg and Cd were the main contributors to the combined effects. In summary, our study indicates that exposure to heavy metal mixtures may increase SUI risk in women.

Bladder neck and urethral erosions after Macroplastique injections.

AIMS: To evaluate the presentation, risk factors, diagnostic workup, management, and outcomes of Macroplastique (MPQ) erosions. METHODS: We performed a retrospective chart review of women experiencing MPQ erosion at two tertiary care centers (United States and United Kingdom). Data collected included age, presenting symptoms, parity, comorbidities, hormone replacement therapy, sexual activity, and smoking status. Previous surgical history, time from MPQ injection, urine culture results, and cystoscopic and imaging findings were also reviewed. Development of stress urinary incontinence (SUI) after MPQ removal and subsequent SUI treatments were recorded. RESULTS: From 2012 to 2018, 18 patients were identified with a median follow-up time of 24 months (interquartile range [IQR] 8-33). All patients presented with recurrent urinary tract infections (rUTI) and had cystoscopic evidence of MPQ erosion. The most common location of erosion was the bladder neck area (72%). Median time to presentation since MPQ injection was 14 months (IQR 11-35). The majority of patients (72%) had a previous history of anti-incontinence surgery. The overall success rate of endoscopic management defined as resolution of presenting symptoms including rUTI was 80%. The majority of patients (80%) developed recurrent SUI following MPQ resection with 33% requiring a subsequent autologous fascial sling placement. CONCLUSION: MPQ erosions present predominantly with UTI, sometimes years after the original injection, and may necessitate endoscopic management with satisfactory results in most patients. Following excision of MPQ, these patients are highly likely to experience SUI recurrence and need to be appropriately counseled. Some may require additional subsequent autologous fascial sling placement for treatment of their SUI symptoms.

Urinary symptoms in women receiving carboplatin/paclitaxel for treatment of gynecologic cancers.

OBJECTIVES: Urinary incontinence is estimated to affect up to 34% of women with gynecologic cancers. Chemotherapeutic effects on urinary symptoms have been scarcely studied. The aim of our study was to examine the impact of carboplatin/paclitaxel chemotherapy on urinary symptoms. METHODS: This was a prospective cohort study of all women undergoing adjuvant chemotherapy with carboplatin/paclitaxel after their primary debulking surgery for ovarian, fallopian tube, peritoneal, or endometrial cancers performed at a tertiary medical center by board certified gynecologic oncologists. We used validated questionnaires (incontinence impact questionnaire (IIQ-7), medical, epidemiologic, and social aspects of aging (MESA), urogenital distress inventory (UDI-6), the Sandvik severity index, and functional assessment of cancer therapy/GynecologicOncology Group-neurotoxicity (FACT/GOG-Ntx)) to assess the effects of carboplatin/paclitaxel therapy on the incidence and severity of urinary incontinence at three time points during the participants' chemotherapy regimen: start of chemotherapy (pretreatment), during the fifth chemotherapy cycle (mid-cycle), and during the 6-12 week post-chemotherapy visit (post-treatment). RESULTS: We identified 62 women with ovarian, fallopian, peritoneal, and endometrial cancer who received carboplatin/paclitaxel therapy between May 2009 and December 2012 who met all of the inclusion criteria. Analysis of median IIQ-7 scores, across all time points, showed a statistically significant difference (0.0 (0.0 to 4.8), 0.0 (0.0 to 7.1), 0.0 (0.0 to 0.0), p=0.002, respectively). Examining pairwise differences between two treatment points, IIQ-7 pretreatment versus mid-treatment and pretreatment versus post-treatment, did not achieve significance (0.0 (0.0 to 2.4), p=0.13 and 0.0 (0.0 to 0.0), p>0.999, respectively), but the decrease in IIQ-7 mid-treatment versus post-treatment was statistically significant (0.0 (-2.4 to 0.0), p=0.003). Generalized estimating equation model analysis also showed significant changes in both median MESA for urge urinary incontinence (MESA-UUI) and median MESA for stress urinary incontinence (MESA-SUI) across all time points (p=0.003 and p=0.009, respectively). MESA-UUI and MESA-SUI pretreatment versus mid-treatment analysis achieved significance (2.0 (0.0 to 4.0), p=0.003 and 0.0 (0.0 to 2.0), p=0.01, respectively), demonstrating an increase in the incidence of stress urinary incontinence and urge urinary incontinence. There was a statistically significant association between the changes in FACT and UDI-6 scores from pretreatment versus mid-treatment, with a correlation coefficient of 0.37 (95% CI 0.08 to 0.61, p=0.005). CONCLUSION: The study achieved its primary aim in demonstrating an impact of carboplatin/paclitaxel therapy on urinary incontinence severity and suggests if may be a factor leading to new onset or worsening urinary incontinence. As quality of life can be significantly impacted by these chemotherapeutic changes, further investigation is warranted to determine if the effects on urinary incontinence and neuropathy are transient or permanent.

Increased risk for stress urinary incontinence in women with postmenopausal hormone therapy.

INTRODUCTION AND HYPOTHESIS: The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI. METHODS: The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis. RESULTS: The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxyprogesterone acetate. Age over 55 years at the initiation of systemic HT was accompanied by a higher SUI risk increase than that under 55 years of age. The use of tibolone, an estradiol + levonorgestrel-releasing intrauterine device, or vaginal estradiol also increased the risk. CONCLUSIONS: The use of HT regimens may predispose to the de novo development or worsening of pre-existing SUI. Thus, caution is needed when these regimens are prescribed to women with mild stress-related urine leakage or with established SUI risk factors.

[Urinary incontinence induced by the antidepressants - case report]. / Mocová inkontinence indukovaná antidepresivy - kazuistické sdelení

AIM: Case study of the patient with urinary incontinence induced by the antidepressant mirtazapin and the review of the related literature. DESIGN: Case Report. SETTING: Department of Urology, University Hospital Ostrava-Poruba. CASE REPORT: A case of 55-years old patiens, who was reffered to the surgical treatment of the urinary incontinence. We found a major discrepancies during the evaluation that led us to suspect that this is not a common uncomplicated case of stress urinary incontinence. Based on the detailed history we identified the antidepressant mirtazapine as a likely causal factor. After discontinuing mirtazapin patient has achieved full control of the continence. CONCLUSION: Given that antidepressants affects adrenergic and dopaminergic regulatory mechanisms in the central nervous system, they may affect the lower urinary tract function. This work presents a case report where the disclosure of the less common cause of incontinence saved the patientoriginally proposed surgical treatment and allowed the effective restoration of the continence. We emphasize the need to consider the potential interaction of antidepressants with lower urinary tract function in daily practice.

A non-invasive method to evaluate the efficacy of human myoblast in botulinum-A toxin induced stress urinary incontinence model in rats.

PURPOSE: To develop a simple non-invasive method to assess the efficacy of a cell based therapy for treating stress urinary incontinence (SUI). MATERIALS AND METHODS: In this study, skeletal myoblasts were used as candidate therapy to reverse SUI. The SUI model was created in rats using periurethral injection of botulinum-A toxin injection. Two weeks later, the rats were administered saline and the level of continence in each botulinum-A toxin treated and control animals was assessed by the extent of voiding using metabolic cages. To determine the efficacy of myoblasts to reverse SUI, botulinum-A toxin treated incontinent rats were injected with either cultured human skeletal myoblasts or with buffered saline (sham control). Two weeks post implantation, the extent of continence was evaluated as mentioned above. RESULTS: The difference in void volume between botulinum-A toxin -treated and control rats were significant. Histological analysis of the urethra showed remarkable atrophy of the muscular layer. A significant reversal (P = .025) in the volume of voiding was observed in cell-implanted rats as compared to sham injected rats. Histological analysis of the urethra implanted with myoblasts showed recovery of the atrophied muscular layer in comparison to sham control. Immunofluorescence analysis of the cell injected tissues confirmed the presence of human myoblasts in the regenerated area. CONCLUSION: This simplified method of in vivo testing can serve as a tool to test the efficacy of new therapies for treating SUI.

The effect of angiotensin inhibition on urinary incontinence: data from the National Health and Nutrition Examination Survey (2001-2008).

INTRODUCTION: Local renin-angiotensin systems exist within the genitourinary tract, specifically in the bladder and urethra. Experimental data suggest that angiotensin receptor blockade with either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) decreases both detrusor overactivity and urethral sphincter tone leading to decreased urge incontinence (UUI) and increased stress urinary incontinence (SUI). This has not been examined in a human population. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) was accessed for the years 2001-2008. Multivariate logistic regression was used for modeling. RESULTS: We studied 8,754 females and 8,886 males who met inclusion criteria. Use of ACE inhibitors or ARBs was not associated with a change in SUI in either men or women. In men, use of an ACE inhibitor or ARB was associated with a statistically significant 25-30% decrease in UUI (monthly or any urge incontinence). A similar, albeit non-significant trend was also seen for daily and weekly UUI. Other antihypertensive medications (diuretics, beta-blockers, calcium-channel blockers) were not associated with a decrease in UUI. In subanalysis, duration of ACE inhibitor or ARB use did not alter the strength of the effect on UUI nor did an elevated prostate specific antigen (PSA) level (used as a surrogate for bladder outlet obstruction due to benign prostatic hypertrophy). ACE inhibitor and ARB use did not affect UUI rates in women, though did show a trend for improvement in nulliparous women without SUI. CONCLUSION: Angiotensin receptor blockade may be a viable treatment approach for the treatment of UUI, especially in men.

Oestrogen therapy for urinary incontinence in post-menopausal women.

BACKGROUND: It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women. This is an update of a Cochrane review first published in 2003 and subsequently updated in 2009. OBJECTIVES: To assess the effects of local and systemic oestrogens used for the treatment of urinary incontinence. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register of trials (searched 21 June 2012) which includes searches of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and handsearching of journals and conference proceedings, and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included oestrogens in at least one arm in women with symptomatic or urodynamic diagnoses of stress, urgency or mixed urinary incontinence or other urinary symptoms post-menopause. DATA COLLECTION AND ANALYSIS: Trials were evaluated for risk of bias and appropriateness for inclusion by the review authors. Data were extracted by at least two authors and cross checked. Subgroup analyses were performed by grouping participants under local or systemic administration. Where appropriate, meta-analysis was undertaken. MAIN RESULTS: Thirty-four trials were identified which included approximately 19,676 incontinent women of whom 9599 received oestrogen therapy (1464 involved in trials of local vaginal oestrogen administration). Sample sizes of the studies ranged from 16 to 16,117 women. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of outcomes.The combined result of six trials of systemic administration (of oral systemic oestrogens) resulted in worse incontinence than on placebo (risk ratio (RR) 1.32, 95% CI 1.17 to 1.48). This result was heavily weighted by a subgroup of women from the Hendrix trial, which had large numbers of participants and a longer follow up of one year. All of the women had had a hysterectomy and the treatment used was conjugated equine oestrogen. The result for women with an intact uterus where oestrogen and progestogen were combined also showed a statistically significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18).There was some evidence that oestrogens used locally (for example vaginal creams or pessaries) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall, there were around one to two fewer voids in 24 hours amongst women treated with local oestrogen, and there was less frequency and urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea.Women who were continent and received systemic oestrogen replacement, with or without progestogens, for reasons other than urinary incontinence were more likely to report the development of new urinary incontinence in one large study.One small trial showed that women were more likely to have an improvement in incontinence after pelvic floor muscle training (PFMT) than with local oestrogen therapy (RR 2.30, 95% CI 1.50 to 3.52).The data were too few to address questions about oestrogens compared with or in combination with other treatments, different types of oestrogen or different modes of delivery. AUTHORS' CONCLUSIONS: Urinary incontinence may be improved with the use of local oestrogen treatment. However, there was little evidence from the trials on the period after oestrogen treatment had finished and no information about the long-term effects of this therapy was given. Conversely, systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence comparing routes of administration. The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods, especially in those women with an intact uterus.

Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence.

PURPOSE: Although caffeine consumption is common and generally believed to affect bladder function, little is known about caffeine intake and incident urinary incontinence. MATERIALS AND METHODS: We performed a prospective cohort study in 65,176 women 37 to 79 years old without incontinence in the Nurses' Health Study and the Nurses' Health Study II. Incident incontinence was identified from questionnaires during 4 years of followup. Caffeine intake was measured using food frequency questionnaires administered before incontinence development. The multivariate adjusted relative risk of the relation between caffeine intake and incontinence risk as well as attributable risk were calculated. RESULTS: Caffeine was not associated with incontinence monthly or more. However, there was a modest, significantly increased risk of incontinence at least weekly in women with the highest (greater than 450 mg) vs the lowest (less than 150 mg) daily intake (RR 1.19, 95% CI 1.06-1.34) and a significant trend of increasing risk with increasing intake (p for trend = 0.01). This risk appeared focused on incident urgency incontinence (greater than 450 vs less than 150 mg daily, RR 1.34, 95% CI 1.00-1.80, p for trend = 0.05) but not on stress or mixed incontinence (p for trend = 0.75 and 0.19, respectively). The attributable risk of urgency incontinence associated with high caffeine intake was 25%. CONCLUSIONS: Findings suggest that high but not lower caffeine intake is associated with a modest increase in the incidence of frequent urgency incontinence. A fourth of the cases with the highest caffeine consumption would be eliminated if high caffeine intake were eliminated. Confirmation of these findings in other studies is needed before recommendations can be made.

Oestrogen therapy for urinary incontinence in post-menopausal women.

BACKGROUND: It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women. OBJECTIVES: To assess the effects of local and systemic oestrogens used for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register of trials (2 April 2009) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included oestrogens in at least one arm, in women with symptomatic or urodynamic diagnoses of stress, urgency or mixed urinary incontinence or other urinary symptoms post-menopause. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the review authors. Data were extracted by at least two authors and cross checked. Subgroup analyses were performed grouping participants under local or systemic administration. Where appropriate, meta-analysis was undertaken. MAIN RESULTS: Thirty- three trials were identified which included 19,313 (1,262 involved in trials of local administration) incontinent women of whom 9417 received oestrogen therapy. Sample sizes ranged from 16 to 16,117. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of outcomes.Systemic administration (of oral oestrogens) resulted in worse incontinence than on placebo (RR 1.32, 95% CI 1.17 to 1.48). This result is heavily weighted by a subgroup of women from the Hendrix trial, which had large numbers of participants and a longer follow up of one year; all the women had had a hysterectomy and the treatment used was conjugated equine oestrogen. The result for women with an intact uterus where oestrogen and progestogen combined were used also showed a statistically significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18).There was some evidence that oestrogens used locally (for example vaginal creams or tablets) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall, there were around one to two fewer voids in 24 hours and nocturnal voids amongst women treated with local oestrogen, and there was less frequency and urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea.Women who were continent and received systemic oestrogen replacement, with or without progestogens, for reasons other than urinary incontinence were more likely to report the development of new urinary incontinence in one large study.The data were too few to address questions about oestrogens compared with or in combination with other treatments, different types of oestrogen or different modes of delivery. AUTHORS' CONCLUSIONS: Local oestrogen treatment for incontinence may improve or cure it, but there was little evidence from the trials on the period after oestrogen treatment had finished and none about long-term effects. However, systemic hormone replacement therapy, using conjugated equine oestrogen, may make incontinence worse. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence on route of administration. The risk of endometrial and breast cancer after long-term use suggests that oestrogen treatment should be for limited periods, especially in those women with an intact uterus.

Vaginal paravaginal repair with porcine dermal reinforcement: correction of advanced anterior vaginal prolapse.

OBJECTIVE: The objective of the study was to determine the efficacy of the vaginal paravaginal repair using porcine dermal graft reinforcement for the correction of advanced anterior vaginal prolapse. STUDY DESIGN: One hundred eleven women underwent reinforced vaginal paravaginal repair between September 2001 and January 2004 and met our inclusion criteria. Postoperatively patients were evaluated at 6 weeks, 6 months, and yearly thereafter. Objective cure was defined as point Ba -1 or less. RESULTS: Eighty-nine of the 111 (80%) patients were available for follow-up. Mean age of patients was 59.5 +/- 11.6 years (range 26 to 82), mean body mass index was 29 +/- 5.5 (range 20 to 44), and median parity was 3 (range 0 to 15). Mean follow-up was 24 +/- 10.1 months (range 6 to 44) with minimum follow-up required for cure of 12 months. Overall cure rate was 78% (68 of 89). Data were analyzed using the Wilcoxon rank test. CONCLUSION: The reinforced vaginal paravaginal repair procedure is safe and effective for correction of advanced anterior vaginal prolapse.

Stress urinary incontinence due to prescription medications: alpha-blockers and angiotensin converting enzyme inhibitors.

BACKGROUND: Several antihypertensive medications affect lower urinary tract function and may cause urinary incontinence. CASE: A 59-year-old woman on doxazosin mesylate for control of her hypertension presented with stress urinary incontinence. Because this drug is known to cause loss of urethral tone leading to stress incontinence in some patients, she was switched to enalapril maleate, an angiotensin converting enzyme inhibitor. Her incontinence improved on the new medication, but she developed a persistent dry cough that continued to cause episodic stress incontinence. Because a persistent cough is a known side effect of angiotensin converting enzyme inhibitors, her medication was changed to a calcium channel blocker, amlodipine besylate. Her cough resolved, and her stress incontinence was no longer a clinical problem. CONCLUSION: Gynecologists should be aware of the unexpected side effects of medications on the lower urinary tract.

Randomized double-blind study comparing the efficacy of terazosin versus placebo in women with prostatism-like symptoms.

PURPOSE: We attempt to determine whether terazosin is effective therapy for the treatment of prostatism-like symptoms in women. MATERIALS AND METHODS: A total of 29 women 47 to 79 years old with prostatism-like symptoms entered a randomized double-blind study comparing terazosin (14) versus placebo (15). The salient inclusion and exclusion criteria consisted of an American Urological Association (AUA) symptom score of 8 or more, post-void residual volume less than 300 ml. and absence of stress urinary incontinence. RESULTS: The baseline and final visit AUA symptom scores were 12.7 and 10.7 respectively, in the placebo group, and 16.4 and 13.6, respectively, in the terazosin group. The differences between the change in AUA symptom score in the placebo and terazosin groups were not clinically or statistically significant. CONCLUSIONS: Our study demonstrates that terazosin is not effective for the treatment of prostatism-like symptoms in aging women.

Urinary incontinence caused by prazosin.

Urinary incontinence is a common problem in elderly women. However, urinary incontinence secondary to the commonly used antihypertensive, prazosin, is a rare phenomenon. The possible mechanism of this drug in causing incontinence is described in this case report. The possibility of an exaggerated response to the drug by women suffering from borderline stress incontinence is highlighted.

Prazosin: a neglected cause of genuine stress incontinence.

Prazosin, a common antihypertensive drug, lowers peripheral vascular resistance by selectively blocking alpha-1 adrenergic receptors on arteriolar smooth muscle. Alpha-1 adrenoceptor inhibition also has a relaxant effect on smooth muscle present in the urethra. Between 1985-1990, 58 of 1335 women (4.3%) seen in our urodynamic clinic with urinary incontinence and other urinary symptoms were taking prazosin. The incidence of genuine stress incontinence was significantly higher in women taking prazosin (86.2%) than in the non-prazosin group (65.7%) (P less than .01). Twenty-five of the 45 women contacted had their urinary incontinence improved or cured by prazosin withdrawal. All of these 25 women with prazosin-related urinary incontinence had stress incontinence. The incidence of previous bladder neck surgery in this group was over 50%, with 11 previous vaginal repairs, one Burch colposuspension, and one Aldridge sling procedure. Seven women who were continent after prazosin withdrawal had their urodynamic studies repeated. There was a significant increase in functional urethral length, maximum urethral closure pressure, and abdominal pressure transmission to the urethra following prazosin withdrawal, although no significant change was found in other cystometric measurements including peak flow rate and residual urine volume. In this study, prazosin was a frequently unrecognized cause of stress incontinence in women, many of whom had unsuccessful and possibly unnecessary surgery.

Misoprostol-induced urinary incontinence.

In a young woman with rheumatoid arthritis misoprostol induced urinary incontinence. The urodynamic study described here revealed a deficiency in urethral resistance which may explain the phenomenon. This side-effect may be more common than expected, and misoprostol should be administered with caution to patients suffering from urinary stress incontinence.