Obesity as an independent risk factor for poor long-term outcome after mid-urethral sling surgery.

INTRODUCTION: High body mass index (BMI) is a risk-factor for stress urinary incontinence (SUI). Mid-urethral sling (MUS) surgery is an effective treatment of SUI. The aim of this study was to investigate if there is an association between BMI at time of MUS-surgery and the long-term outcome at 10 years. MATERIAL AND METHODS: Women who went through MUS surgery in Sweden between 2006 and 2010 and had been registered in the Swedish National Quality Register of Gynecological Surgery were invited to participate in the 10-year follow-up. A questionnaire was sent out asking if they were currently suffering from SUI or not and their rated satisfaction, as well as current BMI. SUI at 10 years was correlated to BMI at the time of surgery. SUI at 1 year was assessed by the postoperative questionnaire sent out by the registry. The primary aim of the study was to investigate if there is an association between BMI at surgery and the long-term outcome, subjective SUI at 10 years after MUS surgery. Our secondary aims were to assess whether BMI at surgery is associated with subjective SUI at 1-year follow-up and satisfaction at 10-year follow-up. RESULTS: The subjective cure rate after 10 years was reported by 2108 out of 2157 women. Higher BMI at the time of surgery turned out to be a risk factor for SUI at long-term follow-up. Women with BMI <25 reported subjective SUI in 30%, those with BMI 25-<30 in 40%, those with BMI 30-<35 in 47% and those with BMI ≥35 in 59% (p < 0.001). Furthermore, subjective SUI at 1 year was reported higher by women with BMI ≥30, than among women with BMI <30 (33% vs. 20%, p < 0.001). Satisfaction at 10-year follow-up was 82% among women with BMI <30 vs 63% if BMI ≥30 (p < 0.001). CONCLUSIONS: We found that higher BMI at the time of MUS surgery is a risk factor for short- and long-term failure compared to normal BMI.

Dyspareunia and pelvic pain: comparison of mid-urethral sling methods 10 years after insertion.

INTRODUCTION AND HYPOTHESIS: The mid-urethral sling (MUS) has been used for more than 30 years to cure stress urinary incontinence. The objective of this study was to assess whether surgical technique affects the outcome after more than ten years, regarding dyspareunia and pelvic pain. METHODS: In this longitudinal cohort study we used the Swedish National Quality Register of Gynecological Surgery to identify women who underwent MUS surgery in the period 2006-2010. Out of 4348 eligible women, 2555 (59%) responded to the questionnaire sent out in 2020-2021. The two main surgical techniques, the retropubic and the obturatoric approach, were represented by 1562 and 859 women respectively. The Urogenital Distress Inventory-6 (UDI-6) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), as well as general questions concerning the MUS surgery, were sent out to the study population. Dyspareunia and pelvic pain were defined as primary outcomes. Secondary outcomes included PISQ-12, general satisfaction, and self-reported problems due to sling insertion. RESULTS: A total of 2421 women were included in the analysis. Among these, 71% responded to questions regarding dyspareunia and 77% responded to questions regarding pelvic pain. In a multivariate logistic regression analysis of the primary outcomes, we found no difference in reported dyspareunia (15% vs 17%, odds ratio (OR) 1.1, 95% CI 0.8-1.5) or in reported pelvic pain (17% vs 18%, OR 1.0, 95% CI 0.8-1.3) between the retropubic and obturatoric techniques among study responders. CONCLUSION: Dyspareunia and pelvic pain 10-14 years after insertion of a MUS do not differ with respect to surgical technique.

Retropubic slings are more efficient than transobturator at 10-year follow-up: a Swedish register-based study.

INTRODUCTION AND HYPOTHESIS: Long-term performance of mid-urethral slings (MUS) and potential differences between the retropubic and the transobturator technique for insertion are scarcely studied. This study aims to evaluate the efficacy and safety 10 years after surgery and compare the two main surgical techniques used. METHODS: Women who underwent surgery with a MUS between 2006 and 2010 were identified using the Swedish National Quality Register of Gynecological Surgery and were invited 10 years after the operation to answer questionnaires regarding urinary incontinence and its impact on quality-of-life parameters (UDI-6, IIQ-7) and impression of improvement, as well as questions regarding possible sling-related complications and reoperation. RESULTS: The subjective cure rate reported by 2421 participating women was 63.3%. Improvement was reported by 79.2% of the participants. Women in the retropubic group reported higher cure rates, lower urgency urinary incontinence rates and lower UDI-6 scores. No difference was shown between the two methods regarding complications, reoperation due to complications or IIQ-7 scores. Persisting sling-related symptoms were reported by 17.7% of the participants, most commonly urinary retention. Mesh exposure was reported by 2.0%, reoperation because of the tape by 5.6% and repeated operation for incontinence by 6.9%, significantly more in the transobturator group (9.1% vs. 5.6%). Preoperative urinary retention was a strong predictor for impaired efficacy and safety at 10 years. CONCLUSIONS: Mid-urethral slings demonstrate good results for the treatment of stress urinary incontinence and tolerable complication profiles in a 10-year perspective. The retropubic approach displays higher efficacy than the transobturator, with no difference regarding safety.

Recurrent surgery in uterine prolapse: A nationwide register study.

INTRODUCTION: One in three women with pelvic organ prolapse (POP) undergoing surgery have a relapse. Currently, no optimal surgical treatment has been identified for correcting a uterine prolapse. This population-based register study aims to compare the relapse rate in patients with uterine prolapse undergoing hysterectomy with suspension or uterine-sparing surgical procedures. MATERIAL AND METHODS: All women with uterine prolapse undergoing prolapse surgery in Sweden from January 1, 2015 to December 31, 2018, were identified from the Gynecological Operation Register (GynOp). The primary outcome was the number of recurrent POP surgeries up to December 31, 2020. RESULTS: Sacrospinous hysteropexy (SSHP) without graft and sacrohysteropexy (SHP) were associated with a significantly higher rate of recurrent POP surgery (SSHP without graft: adjusted odds ratio [aOR] 2.6, 95% CI 2.0-3.5; SHP aOR 2.6, 95% CI 1.8-3.7) and patients describing a sense of globe (SSHP without graft, aOR 2.0, 95% CI 1.6-2.6; SHP, aOR 1.8, 95% CI 1.1-3.1) compared with cervical amputation with uterosacral ligament fixation (Manchester procedure). There was no difference in the reoperation rate or sense of a globe between SSHP with graft and Manchester procedure. Patients undergoing SSHP without graft had a higher frequency of 1-year postoperative complications compared with Manchester procedure (aOR 2.0, 95% CI 1.6-2.6) and SHP (aOR 2.4, 95% CI 1.4-3.9). Moreover, the frequency of 1-year postoperative complications was higher in SSHP with graft (aOR 1.6, 95% CI 1.1-2.2) than in Manchester procedure. CONCLUSIONS: The Manchester procedure was associated with a low rate of recurrent POP surgery, symptomatic recurrence and low surgical morbidity compared with other surgical methods in women with uterine prolapse.

Vaginal vault prolapse and recurrent surgery: A nationwide observational cohort study.

INTRODUCTION: In surgical repair of pelvic organ prolapse the recurrence rate is about 30% and the importance of apical support was recently highlighted. In surgical randomized controlled studies, the external validity can be compromised because the surgical outcomes often depend on surgical volume. Therefore, we sought to study outcomes of surgical treatment in patients with vaginal vault prolapse in a nationwide setting with a variety of surgical volumes. MATERIAL AND METHODS: This is a nationwide cohort study. All patients with a vaginal vault prolapse undergoing surgery, between January 1, 2015 and December 31, 2018, were identified from the Swedish National Quality Register of Gynecological Surgery, GynOp. The primary outcome was the frequency of recurrent pelvic organ prolapse surgery within 2 years postoperatively. Secondary outcomes included patient-reported vaginal bulging, operative time, estimated blood loss and 1-year postoperative complications. RESULTS: In 1812 patients with vaginal vault prolapse, 538 (30%) had a sacrospinous ligament fixation (SSLF) with graft, 441 (24%) underwent SSLF without graft, and 200 (11%) underwent minimally invasive sacrocolpopexy (SCP) or sacrocervicopexy (SCerP). A significantly higher proportion of patients undergoing recurrent pelvic organ prolapse surgery was seen in SSLF without graft than in SSLF with graft (adjusted odds ratio [aOR] 2.2, 95% CI 1.4-3.6). Patient-reported sensation of vaginal bulging 1 year after surgery was higher in the SSLF group without graft than in the SSLF group with graft (aOR 1.9, 95% CI 1.3-2.8) and in the SCP/SCerP group (aOR 2.0, 95% CI 1.1-3.4). Finally, we found a significantly higher rate of complications 1 year after surgery in SSLF without graft (aOR 2.3, 95% CI 1.2-4.2) and in SSLF with graft (aOR 2.2, 95% CI 1.2-4.2) compared with SCP/SCerP. CONCLUSIONS: In patients with vaginal vault prolapse, SSLF without graft was associated with a higher frequency of recurrent pelvic organ prolapse surgery compared with SSLF with graft, and a higher subjective relapse rate compared with SCP/SCerP and SSLF with graft. Additionally, the complication rate 1 year after primary surgery was higher in SSLF both with and without graft than in SCP/SCerP.

Effects of Obesity on Peri- and Postoperative Outcomes in Patients Undergoing Robotic versus Conventional Hysterectomy.

STUDY OBJECTIVE: To assess if women with obesity have increased complication rates compared with women with normal weight undergoing hysterectomy for benign reasons and if the mode of hysterectomy affects the outcomes. DESIGN: Cohort study. SETTING: Prospectively collected data from 3 Swedish population-based registers. PATIENTS: Women undergoing a total hysterectomy for benign indications in Sweden between January 1, 2015, and December 31, 2017. The patients were grouped according to the World Health Organization's classification of obesity. INTERVENTIONS: Intraoperative and postoperative data were retrieved from the surgical register up to 1 year after the hysterectomy. Different modes of hysterectomy in patients with obesity were compared, such as open abdominal hysterectomy (AH), traditional laparoscopic hysterectomy (TLH), vaginal hysterectomy (VH), and robot-assisted laparoscopic hysterectomy (RTLH). MEASUREMENTS AND MAIN RESULTS: Out of 12,386 women who had a total hysterectomy during the study period, we identified 2787 women with normal weight and 1535 women with obesity (body mass index ≥30). One year after the hysterectomy, the frequency of complications was higher in women with obesity than in women with normal weight (adjusted odds ratio [aOR]) 1.4; 95% confidence interval [CI], 1.1-1.8). In women with obesity, AH was associated with a higher overall complication rate (aOR 1.8; 95% CI, 1.2-2.6) and VH had a slightly higher risk of intraoperative complications (aOR 4.4; 95% CI, 1.2-15.8), both in comparison with RTLH. Women with obesity had a higher rate of conversion to AH with conventional minimally invasive hysterectomy (TLH: aOR 28.2; 95% CI, 6.4-124.7 and VH: 17.1; 95% CI, 3.5-83.8, respectively) compared with RTLH. AH, TLH, and VH were associated with a higher risk of blood loss >500 mL than RTLH (aOR 11.8; 95% CI, 3.4-40.5; aOR 8.5; 95% CI, 2.5-29.5; and aOR 5.8; 95% CI, 1.5-22.8, respectively) in women with obesity. CONCLUSION: The use of RTLH may lower the risk of conversion rates and intraoperative bleeding in women who are obese compared with other modes of hysterectomy.

Perineorrhaphy Compared With Pelvic Floor Muscle Therapy in Women With Late Consequences of a Poorly Healed Second-Degree Perineal Tear: A Randomized Controlled Trial.

OBJECTIVE: To evaluate outcomes after pelvic floor muscle therapy, as compared with perineorrhaphy and distal posterior colporrhaphy, in the treatment of women with a poorly healed second-degree obstetric injury diagnosed at least 6 months postpartum. METHODS: We performed a single center, open-label, randomized controlled trial. After informed consent, patients with a poorly healed second-degree perineal tear at minimum 6 months postpartum were randomized to either surgery or physical therapy. The primary outcome was treatment success, as defined by Patient Global Impression of Improvement, at 6 months. Secondary outcomes included the Pelvic Floor Distress Inventory, the Pelvic Floor Impact Questionnaire, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, and the Hospital Anxiety and Depression Scale. Assuming a 60% treatment success in the surgery group and 20% in the physical therapy group, plus anticipating a 20% loss to follow-up, a total of 70 patients needed to be recruited. RESULTS: From October 2015 to June 2018, 70 of 109 eligible patients were randomized, half into surgery and half into tutored pelvic floor muscle therapy. The median age of the study group was 35 years, and the median duration postpartum at enrollment in the study was 10 months. There were three dropouts in the surgery group postrandomization. In an intention-to-treat analysis, with worst case imputation of missing outcomes, subjective global improvement was reported by 25 of 35 patients (71%) in the surgery group compared with 4 of 35 patients (11%) in the physical therapy group (treatment effect in percentage points 60% [95% CI 42-78%], odds ratio 19 [95% CI 5-69]). The surgery group was superior to physical therapy regarding all secondary endpoints. CONCLUSION: Surgical treatment is effective and superior to pelvic floor muscle training in relieving symptoms related to a poorly healed second-degree perineal tear in women presenting at least 6 months postpartum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02545218.

Associations Between Childbirth and Urinary Incontinence After Midurethral Sling Surgery.

OBJECTIVE: To assess whether subsequent childbirths affect the outcomes of midurethral sling surgery with regard to stress urinary incontinence (SUI). METHODS: In this population-based cohort study, we used the validated Swedish nationwide health care registers (the Patient Register and the Medical Birth Register) to identify women with a delivery after midurethral sling surgery (n=207, study group). From the same registers we then randomly identified a control group who had no deliveries after their midurethral sling procedure (n=521, control group). The women in the control group were matched to the women in the study group by age and year of surgery. The Urogenital Distress Inventory and the Incontinence Impact Questionnaire were sent out to the study population. Symptomatic SUI was defined as the primary outcome. Secondary outcomes included the total Urogenital Distress Inventory score, Urogenital Distress Inventory subscale scores, and Incontinence Impact Questionnaire scores. RESULTS: A total of 728 women were eligible for the study. The response rate was 74%; 163 in the study group (64 with vaginal delivery and 95 with cesarean delivery) and 374 women in the control group were included in the analysis. The rate of SUI (primary outcome) was 36 of 163 (22%) in the study group and 63 of 374 (17%) in the control group. In a multivariate regression analysis of the primary outcome, we found no significant difference between the groups (odds ratio [OR] 1.2, 95% CI 0.7-2.0). Vaginal childbirth after midurethral sling surgery did not increase the risk of SUI compared with cesarean delivery (22% vs 22%, OR 0.6, 95% CI 0.2-1.4). There were no significant differences in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores between any of the groups. CONCLUSION: Childbirth after a midurethral sling procedure is not associated with an increased risk of patient-reported SUI, and continence status is not affected by the mode of a subsequent delivery.

Cervical amputation versus vaginal hysterectomy: a population-based register study.

INTRODUCTION AND HYPOTHESIS: Surgical management of uterine prolapse varies greatly and recently uterus-preserving techniques have been gaining popularity. The aim of this study was to compare patient-reported outcomes after cervical amputation versus vaginal hysterectomy, with or without concomitant anterior colporrhaphy, in women suffering from pelvic organ prolapse. METHOD: We carried out a population-based longitudinal cohort study with data from the Swedish National Quality Register for Gynecological Surgery. Between 2006 and 2013, a total of 3,174 patients with uterine prolapse were identified, who had undergone primary surgery with either cervical amputation or vaginal hysterectomy, with or without concomitant anterior colporrhaphy. Pre- and postoperative prolapse-related symptoms and patient satisfaction were assessed, in addition to complications and adverse events. Between-group comparisons were performed using univariate and multivariate logistic regression. RESULTS: There were no differences between the two groups in neither symptom relief nor patient satisfaction. In both groups a total of 81 % of the women reported the absence of vaginal bulging 1 year after surgery and a total of 89 % were satisfied with the result of the operation. The vaginal hysterectomy group had a higher rate of severe complications than the cervical amputation group, 1.9 % vs 0.2 % (p < 0.001). The vaginal hysterectomy group also had a longer duration of surgery and greater perioperative blood loss, in addition to longer hospitalization. CONCLUSIONS: Cervical amputation seems to perform equally well in comparison to vaginal hysterectomy in the treatment of uterine prolapse, but with less morbidity and a lower rate of severe complications.

Does the choice of suture material matter in anterior and posterior colporrhaphy?

INTRODUCTION AND HYPOTHESIS: The optimal suture material in traditional prolapse surgery is still controversial. Our aim was to investigate the effect of using sutures with rapid (RA) or slow (SA) absorption, on symptomatic recurrence after anterior and posterior colporrhaphy. METHODS: A population-based longitudinal cohort study with data from the Swedish National Quality Register for Gynecological Surgery. A total of 1,107 women who underwent primary anterior colporrhaphy and 577 women who underwent primary posterior colporrhaphy between September 2012 and September 2013 were included. Two groups in each cohort were created based on which suture material was used. Pre- and postoperative prolapse-related symptoms and patient satisfaction were assessed. RESULTS: We found a significantly lower rate of symptomatic recurrence 1 year after anterior colporrhaphy in the SA suture group compared with the RA suture group, 50 out of 230 (22 %) vs 152 out of 501 (30 %), odds ratio 1.6 (CI 1.1-2.3; p = 0.01). The SA group also had a significantly higher patient satisfaction rate, 83 % vs 75 %, odds ratio 1.6 (CI 1.04-2.4), (p = 0.03). Urgency improved significantly more in the RA suture group (p < 0.001). In the posterior colporrhaphy cohort there was no significant difference between the suture materials. CONCLUSIONS: This study indicates that the use of slowly absorbable sutures decreases the odds of having a symptomatic recurrence after an anterior colporrhaphy compared with the use of rapidly absorbable sutures. However, the use of RA sutures may result in less urgency 1 year postoperatively. In posterior colporrhaphy the choice of suture material does not affect postoperative symptoms.

Decreased gene expression of fibrillin-1 in stress urinary incontinence.

AIMS: Studies to show impairments in the pelvic floor extracellular matrix (ECM) associated with stress urinary incontinence (SUI) has earlier been performed, but the results are contradictory. Collagen I and III, the elastin associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Their gene signals and tissue localizations were investigated. METHODS: Para-urethral punch biopsies were obtained from 24 women, 12 pre- and 12 postmenopausals, during surgery for SUI. As controls, biopsies were collected from 14 women, 8 pre- and 6 postmenopausals, undergoing surgery for other benign conditions. The mRNA expression by real-time RT-PCR and protein localization by immunohistochemistry were analyzed concerning collagen I and III, the small leucine rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin and the elastic fiber associated proteins fibulin-5 and fibrillin-1. Statistical comparisons controlled for age changes in gene expressions. RESULTS: A significant decrease in mRNA expression of fibrillin-1 was discovered in all SUI women compared to all controls, P = 0.03. All molecules were down-regulated by age, but no other differences between SUI and controls reached significance. All proteins were adequately expressed by immunohistochemistry. A weaker staining for fibrillin-1 was seen in the pre-menopausal SUI group compared to the pre-menopausal controls. CONCLUSIONS: A decreased gene signal and weaker immunoreactivity for fibrillin-1, important for the elastic fiber assembly, was discovered in women with SUI. Loss of tissue elasticity could lead to increased urethra hypermobility and SUI.

Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse.

Few studies are performed on the sustainability of the pelvic floor extracellular matrix important for preventing development of pelvic organ prolapse (POP). Collagens I and III, the elastin-associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Para-urethral biopsies were obtained from 15 women, 6 pre- and 9 post-menopausal, with POP. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry for collagen I, collagen III, fibrillin-1, fibulin-5, decorin, lumican and fibromodulin were performed and compared with 14 controls, 8 pre- and 6 post-menopausal. Statistical comparisons controlled for age changes in gene expressions. A 16-fold decrease in decorin mRNA expression, P = 0.0001, and 8-fold in lumican mRNA expression, P = 0.001, were discovered in premenopausal POP compared with matched controls. In all women with POP, there were lower gene expressions of fibromodulin, P = 0.004, and fibulin-5, P = 0.001, compared with all controls. All proteins were detectable by immunohistochemistry, showing a weaker staining for decorin in premenopausal POP. For the first time, we show substantially decreased gene signal for production of SLRPs, regulators of collagen fiber assembly and impairment in elastic fiber assembly by down-regulation of fibulin-5 in POP.

New concepts and trends in vaginal prolapse surgery.

Despite poor results in prolapse surgery, the operative procedures have basically remained unchanged for 100 years. It has been postulated that lifting restrictions and other measures of inactivation are crucial for the success. Even though most of what is done in prolapse repair is not evidence based, few have challenged the prevailing concepts. However, tradition-based policies are now being scrutinized and in accordance with other operations, time of hospitalization is sharply reduced at many institutions. The reintroduction of local anesthesia and sedation offers potential advantages compared to regional- or general anesthesia. Although augmentation by foreign material is not altogether a new concept, the introduction of commercial kits make mesh procedures more standardized, but not necessarily technically more easy to perform. As molecular biology provides more and more evidence about the importance of the quality of the connective tissue, it is conceivable that foreign material in prolapse repair is here to stay. In this period of time it is more essential than ever to scientifically document the results of the new concepts. In the Nordic countries, where the first registries were set up for Tensionfree Vaginal Tape (TVT), a cooperative effort among 53 institutions is under way to evaluate mesh repairs in prolapse surgery.

Role of proteoglycans in the organization of periurethral connective tissue in women with stress urinary incontinence.

OBJECTIVES: Connective tissue consists of fibroblasts and extracellular matrix (ECM) with collagen and elastic fibers, glycoproteins and proteoglycans (PGs) and it is considered an important factor of the supportive structures of the genitourinary region. Since PGs are essential for the organization of the collagen fibrils in the ECM, we investigated the presence of two PGs, fibromodulin and lumican, and of collagen type I in the periurethral connective tissue from women with stress urinary incontinence (SUI), compared to asymptomatic controls. METHODS: Thirty-two patients participated in the study and they were divided into four groups: premenopausal incontinents, premenopausal controls, postmenopausal incontinents and postmenopausal controls. All patients underwent gynaecologic surgical procedures and punch biopsies from the periurethral tissue were obtained. Immunohistochemistry for collagen type I, fibromodulin and lumican was performed on the histological slides. RESULTS: In premenopausal incontinents the immunoreactivity for collagen type I was weaker with an irregular distribution compared to premenopausal controls; while for fibromodulin, the staining was stronger in premenopausal incontinents than in premenopausal controls. Between the two postmenopausal groups there was not a significant difference in the intensity of collagen type I and fibromodulin staining that instead were less strong than in premenopausal groups. Lumican staining had the same distribution in the four groups. CONCLUSIONS: Our results suggest an altered remodelling of connective tissue in the periurethral region of premenopausal patients with SUI, with a significant decrease of collagen content and an irregular organization and distribution of the collagen fibrils, compared to premenopausal controls. In the SUI patients this abnormal ECM remodelling, mainly related to the observed change in PGs expression, might affect significantly the tensile strength of the connective tissue and consequently the support that is provided by the urogenital suspensory apparatus to urethra and bladder base. Moreover, the significant decrease in collagen type I content in postmenopausal patients respect to premenopausal patients, suggests that age and hormonal factors could contribute to the pathological modifications of the supportive genitourinary connective tissues in the SUI patients.

Pelvic floor sex steroid hormone receptors, distribution and expression in pre- and postmenopausal stress urinary incontinent women.

BACKGROUND: Hormonal influence on stress urinary incontinence (SUI) is under debate. Sex steroid hormonal activity is mediated by nuclear receptor proteins. The aim of this study is to identify receptor isoforms and their genetic expression in the pelvic floor extra cellular matrix (ECM), and to compare women with and without SUI before and after menopause. METHODS: Sub-mucosal para-urethral biopsies from 4 pre-menopausal and 8 postmenopausal patients with SUI were analysed immunohistochemically regarding estrogen receptors (ER) alpha and beta, the progesterone receptor (PR) (A+B) and B, and the androgen receptor (AR). Six pre-menopausal and 5 postmenopausal women served as controls. All receptors were scored manually. Additionally, ER-alpha and ER-beta were quantified by image analysis. Biopsies from 7 pre-menopausal and 7 postmenopausal women suffering from SUI were studied by real-time RT-PCR for expression of ER-alpha, ER-beta, PR and AR. The control group consisted of 5 pre-menopausal and 5 postmenopausal women. RESULTS: Immunohistochemistry revealed receptor-positive cells for all isoforms in all groups. Higher ER-beta scores were seen in the pre-menopausal SUI group compared to controls. Lower PR-B scores were found after menopause in both groups. The image analysis confirmed that ER-beta was significantly increased in the pre-menopausal SUI group compared to controls (p=0.02). By real-time RT-PCR, no difference of mRNA expression regarding any receptor was detected between any SUI and control group. ER-beta mRNA levels were low or undetectable. There was a significant down-regulation of PR among postmenopausal women (p=0.001). CONCLUSIONS: The para-urethral ECM is a target for sex steroid hormones mediated by the respective receptor. The significant higher expression of ER-beta protein in the pre-menopausal SUI-group was not reflected by a corresponding up-regulation of mRNA which was poorly expressed in all groups.

Treatment of panic disorder: live therapy vs. self-help via the Internet.

A randomized trial was conducted comparing 10 individual weekly sessions of cognitive behaviour therapy for panic disorder (PD) with or without agoraphobia with a 10-module self-help program on the Internet. After confirming the PD diagnosis with an in-person structured clinical interview (SCID) 49 participants were randomized. Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail can be equally effective as traditional individual cognitive behaviour therapy. Composite within-group effect sizes were high in both groups, while the between-group effect size was small (Cohen's d=16). One-year follow-up confirmed the results, with a within-group effect size of Cohen's d=0.80 for the Internet group and d=0.93 for the live group. The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.

Young women with genital prolapse have a low collagen concentration.

BACKGROUND: Genital prolapse is a common and handicapping form of pelvic floor dysfunction. To explain its genesis as a result of endopelvic connective tissue weakness, the collagen state was analyzed in women with and without genital prolapse. METHODS: Punch biopsies from the paraurethral ligaments were obtained during the operation from 22 women undergoing surgery for genital prolapse. As controls, similar biopsies were taken from 13 women who underwent gynecologic surgery for other benign reasons. Collagen concentration as hydroxyproline and its extractability by pepsin digestion were studied in relation to age by multiple regression, two-way anova, Levene's test, and Student's t-test. Histological examination was also performed. RESULTS: Women, younger than 53 years, with genital prolapse had a 30% lower collagen concentration than age-matched controls, which reached significance, P = 0.01. The extractability by pepsin digestion, an indicator of cross-links in the collagen molecule, did not significantly differ between groups. It did, however, decrease significantly with age in both prolapse patient and control groups. Morphology supported these findings with a less-dense extracellular matrix composition subepithelially in genital prolapse compared to a healthy control. CONCLUSION: For the first time, we show that young women with genital prolapse have a decreased collagen concentration, suggesting a different organization of the endopelvic connective tissue extracellular matrix. Furthermore, these alterations differ from those earlier found in younger women with stress urinary incontinence.