Role of sex steroid hormones in pelvic organ prolapse.

OBJECTIVE: Pelvic organ prolapse (POP) affects a significant percentage of women and contributes to major healthcare costs both in the United States and worldwide. This review examines the current understanding of the role of sex steroid hormones (estrogens, androgens, and progesterone) in POP in premenopausal, perimenopausal, and postmenopausal women. METHODS: We reviewed the relevant studies on POP related to estrogens, androgens, and progesterone in both animal models and humans. RESULTS: Estrogen has a profound influence on the synthesis and metabolism of pelvic connective tissues, and may have the ability to both prevent POP and improve prognosis if used therapeutically. There is limited research regarding the role of androgens and progesterone and their receptors in POP and results so far have been contradictory, warranting further study to determine whether changes in androgen and progesterone receptor expression are a cause or effect of POP. CONCLUSIONS: Because of the role that estrogen plays in maintaining the integrity of pelvic floor connective tissues, we propose that rigorous and well-controlled studies are needed on the role of exogenous estrogen administration as a form of POP prevention. : Video Summary:http://links.lww.com/MENO/A583.

Video Summary:http://links.lww.com/MENO/A583.

Suppression of lysyl oxidase gene expression by methylation in pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: We measured promoter methylation in the LOX gene in women with pelvic organ prolapse and in women without prolapse. METHODS: Genomic DNA was isolated from the uterosacral ligaments of eight women with prolapse and eight women without prolapse as controls. Genomic DNA was digested with BamHI and underwent sodium bisulfite modification. The LOX gene promoter region of -246 to +74 was then amplified by PCR, cloned into PCR2.1-TOPO and transformed into an Escherichia coli DH5alpha strain. Amplified plasmid DNA samples containing the LOX gene promoter region from each woman were sequenced and methylated CpG islands were identified by sequence comparison. RESULTS: A total of 66 methylated CpG sites were found in the group of patients with prolapse, while only one methylated CpG site was found in the non-prolapse control group. CONCLUSIONS: Methylation in the promoter region may suppress LOX gene expression in women with pelvic organ prolapse.

Assessment of patient outcomes following submucosal injection of triamcinolone for treatment of Hunner's ulcer subtype interstitial cystitis.

INTRODUCTION AND OBJECTIVE: Hunner's ulcer subtype interstitial cystitis (IC) is characterized by the presence of circumscribed inflammatory ulcerations in the bladder wall identified during endoscopic examination of individuals with irritative voiding symptoms and pelvic pain. We present our experience with management of this subgroup with intralesional submucosal injection of corticosteroid. METHODS: Prospective analysis of patients presenting with Hunner's ulcer subtype IC was performed between November 2006 to April 2008. All patients underwent flexible cystoscopy and biopsy confirming the presence of Hunner's ulcer(s). Under general anesthesia, 10 ml of triamcinolone acetonide (40 mg/ml) was injected in 0.5 ml aliquots into the submucosal space of the center and periphery of ulcer(s) using an endoscopic needle. Patient symptoms and quality of life was assessed using two validated questionnaires, the International Prostate Symptom Score (IPSS) and the Pelvic Pain and Urgency/Frequency (PUF) symptom scale. Each questionnaire was administered prior to therapy and 4 weeks postoperatively. The postoperative interview included the Patient Global Impression of Change (PGIC). RESULTS: Thirty patients with Hunner's ulcer subtype IC underwent endoscopic submucosal injection of triamcinolone. The mean preoperative and postoperative IPSS were 21.1 and 11.3, respectively. The mean preoperative and postoperative PUF scores were 20.0 and 11.0, respectively. PGIC assessment revealed 21 of 30 patients (70%) very much improved. No perioperative complications were noted. CONCLUSION: In Hunner's ulcer IC, submucosal injection of triamcinolone is well tolerated. This treatment offers significant improvement in symptoms and quality of life based on responses from validated questionnaires administered before and after therapy.

Interstitial cystitis/painful bladder syndrome for the primary care physician.

Interstitial cystitis also known as painful bladder disorder refers to individuals with chronic bladder inflammation of unknown cause. The presentation of disabling symptoms of urgency, frequency, nocturia, and varying degrees of suprapubic discomfort, is one that the primary care physician will encounter frequently as the prevalence of interstitial cystitis ranges from 10.6 cases per 100,000 to as high as one in 4.5 women, depending upon the criteria used for its diagnosis. Many etiologies are possible. The disorder can be divided clinically into two groups-ulcerative and non-ulcerative-based on cystoscopic findings and response to treatment. In general the diagnosis is made by excluding known treatable causes of bladder irritation. Criteria for the disease are lacking. Management follows an approach of applying the least invasive therapy that affords sufficient relief of symptoms. This monograph attempts to guide the practicing primary care physician from the clinical presentation to a sensible diagnostic work-up and reviews the present management strategies in patients with interstitial cystitis.

Decreased endopelvic fascia elastin content in uterine prolapse.

BACKGROUND: Genital prolapse is a debilitating manifestation of pelvic floor dysfunction. The cause of this condition has not been elucidated. The purpose of this study was to determine elastin content and RNA expression of related enzymes of elastin synthesis in uterosacral ligament biopsies from women with severe prolapse, and controls with normal pelvic support. METHODS: Biopsies were taken from the uterosacral ligament tissue of 31 women with Grade III or greater prolapse and 29 women with normal pelvic support. Elastin content was assessed by measuring desmosine using radioimmunoassay, and quantitative real time PCR was performed to quantify mRNA levels of lysyl oxidase (LOX), lysyl oxidase like-1 (LOXL1), LOXL2 and fibulin-5 (FIB-5). RESULTS: The mean desmosine concentration found in uterosacral ligaments of women with prolapse (n =26) was 103.3+/-59.3 pmolD/mgP compared to controls (n =29) 120.5+/-47.4 pmolD/mgP (p =0.1943). In the subgroup of subjects with complete procidentia (n =8), mean desmosine concentration was 50.6+/-25.8 and 127.1+/-42.2 pmolD/mgP in age-matched controls (n =12) (p <0.05). In tissue from subjects with more than 2 vaginal deliveries (n =18), the mean desmosine concentration was 99.9+/-60.7 and 133.0+/-44.0 pmolD/mgP in controls (n =17) (p <0.05). Expression of LOX, LOXL1 and LOXL2 decreased 8.2-fold+/-3.4, 5.0-fold+/-1.7 and 15.2-fold+/-5.2, respectively (mean+/-SD) in cases versus controls (p<0.05). Expression of FIB-5 was increased 3.1-fold+/-0.7 compared to controls (p<0.05). CONCLUSIONS: Significantly decreased desmosine content was measured in the uterosacral ligament tissue from women with prolapse versus controls in women with parity >2 and in women with complete procidentia. Suppression of mRNA for LOX and two LOX isoenzymes was correspondingly present. These results suggest that altered elastin metabolism is present in women with uterine prolapse.

Effect of transobturator tape procedure on proximal urethral mobility.

OBJECTIVES: To assess prospectively the degree of urethral mobility in the preoperative and postoperative periods after the transobturator tape procedure and correlate the findings with surgical outcome. METHODS: Thirty-six consecutive patients with stress urinary incontinence underwent the transobturator tape procedure. A cotton-swab test was performed before the procedure and at the 6-week postoperative follow-up visit to evaluate proximal urethral mobility. Cure was defined as the absence of leak during cough stress testing at cystometric capacity. RESULTS: Of the 36 patients, 26 were available for the complete follow-up evaluation. The mean preoperative and postoperative resting cotton-swab test values were 11.7 degrees and 13.6 degrees, respectively (P = 0.347). The mean preoperative and postoperative straining cotton-swab test values were 57.3 degrees and 48.4 degrees, respectively (P = 0.047). Of the 36 patients, 21 had a straining cotton-swab test result of 30 degrees or greater after surgery, and 19 (90.4%) of these 21 patients were objectively cured by the procedure. Overall, 21 patients (84%) were objectively cured of stress urinary incontinence. Four patients had urinary leakage during stress testing at cystometric capacity. Three of these patients reported subjective cure and one noted improvement. Of the 5 patients with a negative cotton-swab test after surgery, 2 were cured (50%), 2 were not cured, and 1 did not undergo cough stress testing at cystometric capacity because of urgency at 200-mL limiting bladder filling. CONCLUSIONS: The cure of urodynamic stress incontinence using the transobturator tape procedure does not require the correction of proximal urethral mobility.

Treatment of voiding dysfunction after transobturator tape procedure.

Voiding dysfunction after mid-urethral sling procedures is uncommon but not completely avoidable. We report on a method to adjust the transobturator mid-urethral sling under local anesthesia in the early postoperative period for postoperative voiding difficulty. At postoperative day 17 and 18, 2 women, who had undergone the transobturator tape procedure for stress incontinence, underwent successful loosening of the mesh through the previous vaginal incision, without the need to transect or remove the tape. Both patients had immediate resolution of their symptoms while maintaining urinary continence.

Bladder injury during transobturator sling.

The new minimally invasive transobturator sling for surgical treatment of female genuine stress urinary incontinence is designed to reproduce the natural suspension of the urethral fascia while eliminating the need for retropubic needle passage. We report 3 cases of bladder perforation during the transobturator sling procedure. All injuries were identified intraoperatively by cystoscopy, and successful reinsertion of the mesh was accomplished. Transurethral bladder drainage with a Foley catheter was maintained for 5 to 7 days postoperatively. All 3 patients recovered uneventfully. Routine intraoperative cystoscopy is, therefore, recommended for the identification of bladder injuries during the transobturator sling procedure.