Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial.

OBJECTIVE: This study aims to determine the dose-dependent effects of testosterone on sexual function, body composition, muscle performance, and physical function in hysterectomized women with or without oophorectomy. METHODS: Seventy-one postmenopausal women who previously underwent hysterectomy with or without oophorectomy and had total testosterone levels less than 31 ng/dL or free testosterone levels less than 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were randomized to receive weekly intramuscular injections of placebo or 3, 6.25, 12.5, or 25 mg of testosterone enanthate for 24 weeks. Total and free testosterone levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. The primary outcome was change in sexual function measured by the Brief Index of Sexual Functioning for Women. Secondary outcomes included changes in sexual activity, sexual distress, Derogatis Interview for Sexual Functioning, lean body mass, fat mass, muscle strength and power, and physical function. RESULTS: Seventy-one women were randomized; five groups were similar at baseline. Sixty-two women with analyzable data for the primary outcome were included in the final analysis. The mean on-treatment total testosterone concentrations were 19, 78, 102, 128, and 210 ng/dL in the placebo, 3-mg, 6.25-mg, 12.5-mg, and 25-mg groups, respectively. Changes in composite Brief Index of Sexual Functioning for Women scores, thoughts/desire, arousal, frequency of sexual activity, lean body mass, chest-press power, and loaded stair-climb power were significantly related to increases in free testosterone concentrations; compared with placebo, changes were significantly greater in women assigned to the 25-mg group, but not in women in the lower-dose groups. Sexual activity increased by 2.7 encounters per week in the 25-mg group. The frequency of androgenic adverse events was low. CONCLUSIONS: Testosterone administration in hysterectomized women with or without oophorectomy for 24 weeks was associated with dose and concentration-dependent gains in several domains of sexual function, lean body mass, chest-press power, and loaded stair-climb power. Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects.

Modified approach to vaginal hysterectomy without initial colpotomy.

PURPOSE OF REVIEW: To evaluate the surgical technique and outcomes of women undergoing the modified approach to vaginal hysterectomy at Harbor-University of California, Los Angeles Medical Center from 2000 to 2011. A retrospective chart review was performed of all vaginal hysterectomy cases performed using the modified technique. RECENT FINDINGS: There is much evidence in favor of the safety of vaginal hysterectomy over other modes of hysterectomy, such as the lower overall incidence of vaginal cuff dehiscence, shorter hospital stays and faster recovery from surgery. The traditional method of performing vaginal hysterectomy involves early anterior or posterior colpotomy. At times, this may be difficult secondary to a flush cervix, distorted anatomy, and adhesions from prior surgeries or infection. At our teaching institution, however, we have adopted a different technique, initially developed by Dr. Reza Mohajer who is one of our faculty members and co-author of this article, that facilitates ligation of uterine vessels without initial attempt at colpotomy. This enables Ob/Gyn residents to safely and successfully perform vaginal hysterectomies despite large uterine size, nulliparity, flush cervix and previous pelvic surgery. SUMMARY: Modified approach to difficult vaginal hysterectomy facilitates performance of vaginal hysterectomy without need for initial anterior or posterior colpotomy.

Urinary retention and voiding dysfunction in women with uterine leiomyoma: a case series.

OBJECTIVE: To examine urinary retention as an underreported complication of uterine leiomyoma. Reproductive-aged women with uterine leiomyoma often describe pelvic pressure and menorrhagia, however few complain of complete urinary retention. STUDY DESIGN: We dis-cuss the cases of 8 women who presented to our emergency room with acute urinary retention over a 4-year period. RESULTS: Patients had a mean age of 39 (range, 25-51) and median parity of 1 (range, 0-5). Seven of 8 patients (88%) had posterior-fundal leiomyomas. All patients underwent either myomectomy or hysterectomy with resolution of their urinary retention. CONCLUSION: Incarceration of the posterior or fundal leiomyoma beyond the pelvic brim can push the cervix against the pubic bone, resulting in compression of the bladder neck or urethra. This may explain the etiology of retention and/or voiding dysfunction in some cases. Urinary retention, as a result of leiomyoma, may be overlooked in the initial management of symptomatic patients.

Development of stem cell therapy for stress urinary incontinence.

PURPOSE OF REVIEW: In recent years, stem cell therapy has been investigated as a promising approach for the treatment of stress urinary incontinence (SUI). This article reviews the biology of stem cells and their applications as a cell-based treatment for SUI. The current status and future direction of this forefront research in urinary incontinence are also examined. RECENT FINDINGS: During the past decade, adult stem cells have been studied as a potential cell-based approach for the treatment of SUI. The results of current preclinical and clinical studies are presented. These studies demonstrated the improvement in histologic and functional outcomes with stem cell therapies for SUI. Adult stem cells may augment sphincter regeneration and also release trophic factors, promoting vessel and nerve integration into the generated tissues. So far, the findings of the clinical trials are less impressive than the results obtained with animal studies. SUMMARY: Although stem cell therapy holds much promise for SUI, the clinical applications in patients have been slow to materialize. This challenge, together with the currently limited data on basic science studies and clinical trials, will undoubtedly stimulate new investigations in the near future.

Urogenital fistula.

This review summarizes the available evidence in the literature on the etiology, diagnosis, management, and prevention of vesicovaginal, urethrovaginal, ureterovaginal, vesicocervical, and vesicouterine fistulae. Urogenital fistula is divided by origin: obstetric fistula occurring predominantly in developing countries and iatrogenic fistula, the most common cause in developed countries.

Sacrospinous ligament fixation for pelvic organ prolapse in the era of vaginal mesh kits.

PURPOSE OF REVIEW: To examine the sacrospinous ligament as a point of attachment for pelvic organ prolapse procedures, including vaginal mesh kits. RECENT FINDINGS: Pelvic surgeons are increasingly employing the sacrospinous ligament as a point of attachment for biologic grafts and synthetic mesh kits during uterovaginal prolapse repairs. These techniques may have introduced a novel set of complications (mesh extrusion, erosion) in addition to those already known to occur in traditional sacrospinous ligament fixations. Except for limited short-term results, little data are available in the literature regarding surgical outcomes and complications for mesh and graft augmented repairs attached to the sacrospinous ligament. SUMMARY: The sacrospinous ligament fixation is a well tolerated and effective procedure for suspension of the vaginal apex. Mesh augmentation using the sacrospinous ligament may improve objective prolapse recurrence, but complications still occur, including those specific to mesh placement.

Uterosacral ligament vaginal vault suspension using delayed absorbable monofilament suture.

INTRODUCTION AND HYPOTHESIS: We investigated the incidence of suture complications and recurrent prolapse following uterosacral ligament suspension (USLS) using delayed absorbable polyglyconate monofilament suture (Maxon). METHODS: We reviewed the medical records of subjects who underwent vaginal USLS using polyglyconate suture. Primary outcomes were suture complications and anatomic failures defined as recurrent apical prolapse stage 1 or greater. Secondary outcomes were subjective failures and reoperation rate for apical prolapse. RESULTS: Fifty-seven out of 68 subjects who underwent USLS with polyglyconate suture over the study period were included in analysis. At median follow-up of 12 months, 3.5% had suture complications. The anatomic and symptomatic failure rate was 7%. One subject underwent repeat surgery for prolapse. CONCLUSIONS: Suture complications are uncommon using polyglyconate suture for USLS, and failure rates are low. This is in comparison to a 44.6% suture erosion rate with permanent suture reported by our institution using the same surgical technique.

Improving resident screening and workup of urinary incontinence in an OB/GYN residency program: a randomized controlled study.

OBJECTIVES: : With an aging US population, an increased prevalence of urinary incontinence, rising health care costs, and a disease that remains largely unidentified, there is an immediate need to train physicians to screen for and treat incontinence. We aim to evaluate resident physician screening of urinary incontinence with a chart-based review. METHODS: : This study entailed 2 parts: a retrospective chart review (part 1) and a prospective randomized trial (part 2). Charts of 200 patients were retrospectively evaluated for documentation of bladder symptoms and incontinence for part 1. In part 2, patients' charts were prospectively randomized to receive a chart-alert sticker ("Do you leak urine?") that reminded resident physicians to ask about urinary incontinence in their general gynecology clinics. The primary outcome was documentation of urinary incontinence. Secondary outcomes were initiation of workup, diagnoses made, and treatment plans. Overall, 200 charts were needed for the prospective study to provide 80% power. RESULTS: : Residents documented any type of bladder symptom (incontinence, urgency, frequency, dysuria, nocturia) in 32 (16.3%) of 196 charts in part 1 and 45 (23.7%) of the 190 randomized charts in part 2 (P = 0.154). In the prospective study, 88 included charts were randomized to receive the "Do you leak urine?" chart-alert sticker and 102 were randomized to no sticker. Residents documented that they asked about incontinence in 30 (34.1%) of the charts with stickers versus 4 (3.9%) of the charts without (P = 0.001). CONCLUSIONS: Overall, the rate that resident physicians inquired about incontinence increased with the alert-sticker from 4% to 34%. Directed education will likely further this improvement.

Suture complications in a teaching institution among patients undergoing uterosacral ligament suspension with permanent braided suture.

INTRODUCTION AND HYPOTHESIS: Our study aimed to identify the rate of suture complications over a 5-year period using braided permanent suture for uterosacral ligament suspension (USLS) surgery. METHODS: We reviewed the medical records of patients who underwent vaginal uterosacral ligament suspensions using braided polyester suture. Outcome measures included rate and timing of suture complications, patient symptoms post-operatively, efficacy of treatment modalities and surgical success. RESULTS: Eighty-three patients had undergone USLS with braided, polyester suture over the study period that met inclusion criteria. Thirty-seven patients (44.6%) had suture-related complications post-operatively with a mean follow-up of 10.4 months. When only silver nitrate was applied, 16.7% improved, and when the suture was cut in clinic, 77.8% resolved. CONCLUSIONS: Permanent polyester braided suture for suspension of vaginal vault may lead to an unacceptably high suture erosion rate, cutting the suture in clinic results in the highest resolution.

Stimulating vaginal repair in rats through skeletal muscle-derived stem cells seeded on small intestinal submucosal scaffolds.

OBJECTIVES: Grafts are used for vaginal repair after prolapse, but their use to carry stem cells to regenerate vaginal tissue has not been reported. In this study, we investigated whether 1) muscle-derived stem cells (MDSC) grown on small intestinal submucosa (SIS) generate smooth-muscle cells (SMC) in vitro and upon implantation in a rat model of vaginal defects; 2) express markers applicable to the in-vivo detection of vaginal endogenous stem cells; and 3) stimulate the repair of the vagina. METHODS: Mouse MDSC grown on monolayer, SIS, or polymeric mesh, were tested for cell differentiation by immunocytochemistry, Western blot and real-time polymerase chain reaction (PCR). Stem cell markers were screened by DNA microarrays followed by real-time PCR, immunocytochemistry, and Western blot. Rats that underwent hysterectomy and partial vaginectomy were left as such or implanted in the vagina with 4',6-Diamidino-2-Phenylindole (DAPI)-labeled MDSC on SIS, or SIS without MDSC, immunosuppressed, and killed at 2-8 weeks. Immunofluorescence, hematoxylin-eosin, and Masson trichrome were applied to tissue sections. RESULTS: Muscle-derived stem cell cultures on monolayer and on scaffolds differentiate into SMC, as shown by alpha-smooth muscle actin (ASMA), calponin, and smoothelin markers. Muscle-derived stem cells express embryonic stem cell markers Oct-4 and nanog. Dual DAPI/ASMA fluorescence indicated MDSC conversion to SMC. Muscle-derived stem cells/SIS stimulated vaginal tissue repair, including keratin-5 positive epithelium formation and prevented fibrosis at 4 and 8 weeks. Oct-4+ putative endogenous stem cells were identified. CONCLUSION: Muscle-derived stem cells/SIS implants stimulate vaginal tissue repair in the rat, thus autologous MDSC on scaffolds may be a promising approach for the treatment of vaginal repair.

Impact of urodynamic based incontinence diagnosis on quality of life in women.

AIMS: To characterize the effect of urodynamic diagnosis on degree of incontinence related bother and health related quality of life in a large, multi-ethnic population of women. METHODS: Effects of multichannel urodynamic diagnosis, urethral competency, and other patient characteristics on abbreviated Urogenital Distress Inventory (UDI6) and Incontinence Impact Questionnaire (IIQ7) composite scores were analyzed retrospectively. RESULTS: Six hundred eleven patients were included. Mean UDI6 and IIQ7 scores were significantly higher among patients with mixed incontinence, detrusor overactivity, urinary stress incontinence with overactive bladder, and negative studies compared to those with stress incontinence without OAB. The relative composite UDI6 and IIQ7 mean scores did not significantly differ between the mixed incontinence, detrusor overactivity, stress incontinence with OAB and negative study groups. UDI6 and IIQ7 scores were significantly higher among stress incontinent patients with intrinsic sphincter deficiency, but similar among mixed incontinent patients with intrinsic sphincter deficiency. CONCLUSION: Urodynamic diagnoses of detrusor overactivity, mixed incontinence, and stress incontinence with overactive bladder are associated with significantly worse incontinence related bother and health related quality of life when compared to those with stress incontinence without OAB. These conditions appear to have similar degree of impact on incontinence related bother and quality of life. Patients presenting with symptoms of incontinence can suffer a similar compromise in quality of life despite a negative MCUD study.

Lower urinary tract dysfunctions in women with diabetes mellitus.

PURPOSE OF REVIEW: This review discusses published data of the recent advances in understanding lower urinary tract dysfunctions in women with diabetes mellitus. RECENT FINDINGS: Many studies have shown a relationship between diabetes mellitus and lower urinary tract dysfunctions. Although the pathophysiology of these disorders is multifactorial, microvascular damage and neuropathy causing dysfunctions of smooth muscle, urothelium, and neuronal components in the lower urinary tract are the most likely etiologies. SUMMARY: Lower urinary tract dysfunctions are common in diabetes mellitus. Screening and effective management of these disorders should be promoted in an effort to decrease morbidity and improve quality of life.

Update on the utilization of grafts in pelvic reconstruction surgeries.

PURPOSE OF REVIEW: Implanted grafts are increasingly used by pelvic reconstructive surgeons and gynecologists. In addition, the marketing of a variety of grafts has been aggressively expanded without scientific evidence to support their use. This review aims to provide an update of the current status and role of grafts in reconstructive pelvic surgery and to review the current knowledge of the biology of currently marketed synthetic and biologic grafts. RECENT FINDINGS: Xenografts are preferable to human tissue-banked grafts due to more predictable integrity. How these biomaterials compare to synthetics in terms of surgical outcomes has not been well studied, however. Absorbable materials that mimic some behaviors of synthetic and biological materials have been developed. Furthermore, several new techniques have been advocated with limited studies. SUMMARY: While the reduction of surgical failure rates in vaginal surgery is desirable, the addition of graft materials must demonstrate improvement in anatomical, functional, and quality of life outcomes over time. Furthermore, future complications due to improper placement or movement of a graft and the possible shrinkage of the graft are of concern. Therefore, significant research is necessary for the preclinical testing of materials, and expertise needs to be developed for the management of complications.

Dyspareunia and chronic pelvic pain after polypropylene mesh augmentation for transvaginal repair of anterior vaginal wall prolapse.

Synthetic mesh augmentations for pelvic floor reconstructive surgeries are increasing in usage and popularity. Many studies are focusing on the anatomical success rates of transvaginal anterior compartment repairs with synthetic mesh, with minimal attention on its postoperative complications. We present a case report on a 59-year-old postmenopausal woman who underwent an anterior repair with 6x4-cm polypropylene mesh. Postoperatively, she developed severe dyspareunia and debilitating chronic pelvic pain. The patient failed conservative medical therapy and now requests complete removal of the synthetic mesh.

Tension-free transobturator tape procedure for stress urinary incontinence.

PURPOSE OF REVIEW: Recent data on the tension-free transobturator tape procedure for the treatment of female stress urinary incontinence are reviewed. RECENT FINDINGS: Although long-term data are not available, the effectiveness and safety of the tension-free transobturator tape procedure as reported during the past 5 years are very promising and this procedure is becoming a popular surgical treatment for female stress urinary incontinence. The continence rates obtained have been similar to those obtained using the retropubic tension-free vaginal tape on short-term follow-up. Clinical data as well as studies on cadaveric dissections suggest that complication rates can be decreased significantly with the transobturator approach. In the original tension-free transobturator tape procedure, the tape is inserted through the obturator foramen from the outside-to-inside direction (skin incision to vaginal incision). The inside-to-outside approach with passage of the tape from the vaginal incision to the obturator foramen has also been described. SUMMARY: The tension-free transobturator tape procedure provides a useful alternative to the retropubic tension-free vaginal tape approach while maintaining the principles of tension-free midurethral support. By avoiding the intrapelvic and retropubic passage, complications can be decreased. The effectiveness of this approach is similar to that of tension-free vaginal tape on short-term follow-up.

Newer pharmacologic options in management of overactive bladder syndrome.

PURPOSE OF REVIEW: Urinary incontinence is an under-reported epidemic that currently affects an estimated 13 million people in the United States, of whom about 11 million are women, according to the National Institute of Diabetes and Digestive and Kidney Diseases (Publication No. 02-4132). Because many patients are unaware of curative options and perceive it to be an inevitable outcome of advancing age, they fail to report their symptoms and increase their risk of developing associated co-morbid disease. Failure to diagnose and treat this condition increases financial burdens on individuals, their families and health care organizations. RECENT FINDINGS: Pharmacologic therapy of urge incontinence previously had limited treatment success because efficacious drugs were poorly tolerated, resulting in low patient compliance. Tolerance and effectiveness continue to be improved due to innovative new drugs and alternative delivery systems. SUMMARY: The goal of this review is to update the clinician on the efficacy and the tolerability of established and investigational pharmacologic modalities of therapy.

Intravesical injection of botulinum toxin for the treatment of overactive bladder.

PURPOSE OF REVIEW: In recent years, botulinum toxin has been investigated for the treatment of various types of lower urinary tract dysfunctions. This review discusses recently published data related to the therapeutic applications of botulinum toxin in overactive bladder as well as the effects of repeated doses, cross-reactivity between different serotypes, and side effects of the toxin injection into the detrusor muscle. RECENT FINDINGS: Botulinum toxin A has been employed initially in the treatment of neurogenic detrusor overactivity in spinal cord injured patients. Since then, several reports, including a large multicenter study, have confirmed the therapeutic effects of this neurotoxin. The application of botulinum toxin A was extended to the treatment of idiopathic detrusor overactivity and similar results were obtained. Repeated injections of botulinum toxin A had the same sustained benefit. Recently, botulinum toxin B was investigated for the treatments of both neurogenic and idiopathic detrusor overactivity as well as for the management of botulinum toxin A resistant cases. SUMMARY: Although intradetrusal injection of botulinum toxin is not yet an approved treatment for overactive bladder, available data suggest that botulinum toxin can be a therapeutic option in patients with neurogenic and nonneurogenic detrusor overactivity who are refractory to anticholinergic medications. There is a need, however, for further investigation to determine the optimal conditions for these applications. A randomized, double-blinded, placebo-controlled trial to evaluate the therapeutic effects of botulinum toxin is under way.

Reevaluating occult incontinence.

PURPOSE OF REVIEW: Occult incontinence is a controversial subject without significant exposure in the literature. Conventionally, it has been assumed to be a marker for increased risk of postoperative stress urinary incontinence (POSUI) after repair of pelvic organ prolapse. The controversy surrounds the performance of prophylactic incontinence procedures based on this assumption. Until 2004 no article in the English language had been published demonstrating an association between occult incontinence and increased risk of stress urinary incontinence after repair of severe pelvic organ prolapse in previously continent women. We will explore the evidence regarding occult incontinence, review the data on intervention trials, and address questions that remain. RECENT FINDINGS: The limited evidence suggests 11-22% of continent patients with severe pelvic organ prolapse will develop POSUI. New evidence suggests that patients with occult incontinence are at substantially more risk. Since anti-incontinence procedures in patients with occult incontinence reduces the incidence of POSUI (to 0-15%), there appears to be some benefit from screening and intervention. Most studies on the subject are small and limited by their design. Results differ regarding whether a negative stress test can be used to rule out the risk of POSUI. SUMMARY: Minimal existing evidence in the English language suggests that patients with occult incontinence are at increased risk of POSUI. Outcomes in occult incontinence patients undergoing repair of pelvic organ prolapse need systematic study. Until there is adequate solid evidence on the predictive values of our screening test, we cannot counsel patients regarding our ability to prevent POSUI or protect them from unnecessary procedures.