The Impact of Systemic Sclerosis on Sexual Health: An Italian Survey.

OBJECTIVE: To evaluate the impact of systemic sclerosis (SSc) on vulvovaginal atrophy (VVA) and sexual health in an Italian population. METHODS: An Italian survey about the prevalence and severity of VVA (on a 0 to 10 scale) and sexual dysfunction (using the Female Sexual Function Index-FSFI) through an anonymous online questionnaire. We investigated couple relationships and intimacy with partners, the predisposition of patients to talk about their sexual problems, physicians' receptivity, and treatment scenarios. Risk factors for VVA symptoms and sexual dysfunction were assessed. RESULTS: A total of 107 women affected by SSc were enrolled. Of these, 83.2% of women (89/107) complained about VVA symptoms and 89.7% (among sexually active women; 87/97) about sexual dysfunction. Menopausal status did not affect VVA symptoms, while age was the only independent risk factor for sexual dysfunction. About 70% (74/107) of women reported a negative impact of disturbances on intimacy with their partner. A total of 63 women (58.9%) had never discussed their sexual problems and VVA condition with a physician. Lubricants were the only treatment prescribed, and 75% of women would welcome new therapies, even if experimental (62.9%). CONCLUSIONS: In women with SSc, VVA symptoms and sexual dysfunction are highly prevalent, independently from menopause. In more than half of the investigated women with SSc, we found reluctance to talk about their sexual problems, despite being symptomatic. This should encourage physicians to investigate vulvovaginal and sexual health. SSc patients would welcome the advent of new treatment possibilities for their VVA and sexual complaints.

A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections.

BACKGROUND: The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. OBJECTIVE: To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml). INTERVENTION: The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ2 and Fisher's exact tests; a p value <0.05 was considered significant. RESULTS AND LIMITATIONS: Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated. CONCLUSIONS: The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs. PATIENT SUMMARY: Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo.

Current challenges in the pharmacological management of genitourinary syndrome of menopause.

INTRODUCTION: Genitourinary syndrome of menopause is caused by climacteric estrogens drop and leads to bothersome and progressive genital and urinary symptoms. Considering the high frequency in the population and the impact on quality of life, it is crucial to find a safe and effective treatment. Pharmacological therapies aim to modulate the hormonal system and reverse tissue changes due to hypoestrogenism and consequently the symptoms. AREAS COVERED: We analyzed the scientific evidence concerning the main pharmacological treatments, which include systemic and topical estrogens, prasterone and ospemifene. This literature review focused on recent safety and efficacy findings in an attempt to identify the best treatment choice for each individual patient. EXPERT OPINION: There are encouraging data regarding the efficacy of all currently available pharmacological options and concerning their short and long-term safety. There are still doubts regarding best treatment choice for oncological high-risk population, in particular for breast cancer survivors, and some issues relative to patients' poor compliance and treatment adherence. For these reasons further studies need to be conducted with a patient-tailored focus.

New Innovations for the Treatment of Vulvovaginal Atrophy: An Up-to-Date Review.

Vulvovaginal atrophy (VVA) is a chronic progressive disease involving the female genital apparatus and lower urinary tract. This condition is related to hypoestrogenism consequent to menopause onset but is also due to the hormonal decrease after adjuvant therapy for patients affected by breast cancer. Considering the high prevalence of VVA and the expected growth of this condition due to the increase in the average age of the female population, it is easy to understand its significant social impact. VVA causes uncomfortable disorders, such as vaginal dryness, itching, burning, and dyspareunia, and requires constant treatment, on cessation of which symptoms tend to reappear. The currently available therapies include vaginal lubricants and moisturizers, vaginal estrogens and dehydroepiandrosterone (DHEA), systemic hormone therapy, and Ospemifene. Considering, however, that such therapies have some problems that include contraindications, ineffectiveness, and low compliance, finding an innovative, effective, and safe treatment is crucial. The present data suggest great efficacy and safety of a vaginal laser in the treatment of genital symptoms and improvement in sexual function in patients affected by VVA. The beneficial effect tends to be sustained over the long-term, and no serious adverse events have been identified. The aim of this review is to report up-to-date efficacy and safety data of laser energy devices, in particular the microablative fractional carbon dioxide laser and the non-ablative photothermal Erbium-YAG laser.

Menopause and female sexual dysfunctions.

Biological and psycho-relational factors contribute equally to the development of sexual symptoms and associated distress, a key element to diagnose female sexual dysfunctions (FSDs) in menopausal women. Consultation at midlife represents an optimal time to discuss sexual life, and healthcare providers have to be proactive in rising the conversation, as patients may not report their sexual concerns spontaneously. An accurate sexual history is essential to characterize the primary symptom, determine the impact on patient's quality of life and identify risk and precipitating factors. Among FSDs, hypoactive sexual desire disorder is very frequent at midlife together with genitourinary syndrome of menopause, a chronic condition negatively affecting the full sexual response. A multidimensional approach targeted to the patient's characteristics, goals and expectations is mandatory and should start from educative counselling and correction of modifiable risk factors. When specific treatments are required, they should include non-pharmacological and pharmacological options, often prescribed in combination to address concomitantly the biological and psychosocial components of FSDs.

CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a widespread condition with a great impact on quality of life and self-image. AIM: We aimed to systematically review the current literature on CO2-Laser therapy efficacy for the treatment of GSM. METHODS: MEDLINE and Embase databases were systematically queried in December 2020 Studies included women with a diagnosis of Vulvo-Vaginal Atrophy (VVA) or GSM without an history of gynaecological and/or breast cancer, pelvic organ prolapse staged higher than 2, pelvic radiotherapy or Sjogren's Syndrome. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021238121. OUTCOMES: Effects of CO2-Laser therapy on GSM symptoms assessed through subjective or objective efficacy measurement methods. RESULTS: A total of 803 articles were identified. Of these, 25 studies were included in this review for a total of 1,152 patients. All studies showed a significant reduction in VVA and/or GSM symptoms (dryness, dyspareunia, itching, burning, dysuria). The pooled mean differences for the symptoms were: dryness -5.15 (95% CI:-5.72,-4.58; P < .001; I2:62%; n = 296), dyspareunia -5.27 (95% CI:-5.93,-4.62; P < .001; I2:68%; n = 296), itching -2.75 (95% CI:-4.0,-1.51; P < .001; I2:93%; n = 281), burning -2.66 (95% CI:-3.75, -1.57; P < .001; I2:86%; n = 296) and dysuria -2.14 (95% CI:-3.41,-0.87; P < .001; I2:95%; n = 281). FSFI, WHIS and VMV scores also improved significantly. The pooled mean differences for these scores were: FSFI 10.8 (95% CI:8.41,13.37; P < .001; I2:84%; n = 273), WHIS 8.29 (95% CI:6.16,10.42; P < .001; I2:95%; n = 262) and VMV 30.4 (95% CI:22.38,38.55; P < .001; I2:24%; n = 68). CO2-Laser application showed a beneficial safety profile and no major adverse events were reported. CLINICAL IMPLICATIONS: Vaginal laser treatment resulted in both a statistically and clinically significant improvement in GSM symptoms. FSFI improved significantly in all 8 included studies but it reached a clinically relevant level only in 2 of them. STRENGTHS & LIMITATIONS: The strength of the current meta-analysis is the comprehensive literature search. We reported data from a high number of patients (1,152) and high number of laser applications (more than 3,800). The main limitations are related to the high heterogeneity of the included studies investigating laser effects. Moreover, most of them are single center and nonrandomized studies. CONCLUSION: The data suggest that CO2-Laser is a safe energy-based therapeutic option for the management of VVA and/or GSM symptoms in postmenopausal women; however, the quality of the body of evidence is "very low" or "low". Filippini M, Porcari I, Ruffolo AF, et al., CO2-Laser therapy and Genitourinary Syndrome of Menopause: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:452-470.

Single-incision mini-sling and trans-obturator sling for stress urinary incontinence: A 5-year comparison.

OBJECTIVE: The aim of our study was to compare objective and subjective outcomes in women with stress urinary incontinence (SUI) submitted to either trans-obturator sling (TVT-ABBREVO®) or single incision mini-sling (SIMS-ALTIS®) at 5-year follow up. STUDY DESIGN: A monocentric, retrospective study including women with isolated SUI and with concomitant proved urodynamic stress incontinence (USI), treated with an TVT-ABBREVO® or SIMS-ALTIS®. At 60-month follow up each woman was assessed subjectively, with two validated questionnaires (UDI-6 and ICQI-SF), and objectively with a cough stress test. Adverse events were collected. RESULTS: Forty-two patients were evaluated in the ABBREVO® group and 58 in the ALTIS® group. No significant difference was found in subjective (88.1% vs 89.7%, p = 0.806) and objective (81.0% vs 86.2%, p = 0.479) cure rates between the two groups. Subjectively, improvement in urinary distress after surgery resulted statistically significant in both groups compared to baseline (p < 0.001). Long-term post-operative complications rate (i.e. de novo OAB and sling exposure) was similar in the two groups. They were, in fact, mainly classified as Dindo II grade and conservatively managed (i.e. antimuscarinics or ß3 agonists for de novo OAB). CONCLUSION: This comparative study did not reveal significant difference between single-incision (ALTIS®) and trans-obturator (TVT-ABBREVO®) slings in terms of efficacy and morbidity at 5-year follow up.

Prevalence and severity of pelvic floor disorders in pregnant and postpartum women.

OBJECTIVE: This multicenter study aimed to evaluate risk factors, prevalence and severity of pelvic floor disorders (PFDs) as well as their consequences on women's emotional well-being, using a questionnaire validated specifically for pregnancy and postpartum. METHODS: Prospective study conducted in eight teaching hospitals in Italy and Italian-speaking Switzerland. Pregnant and postpartum women completed the Italian Pelvic Floor Questionnaire for Pregnancy and Postpartum anonymously. Prevalence of, severity of, and risk factors for PFDs were evaluated for all the four domains considered: bladder, bowel, prolapse, and sexual function. RESULTS: A total of 2007 women were included: 983 of the patients were bothered by at least one kind of PFD: bladder, bowel, and sexual dysfunction were more frequently reported. There were no significant differences in PFD prevalence between pregnancy and postpartum, except for bladder disorders, which were more prevalent in pregnancy. Familiarity for PFDs, pelvic floor contraction inability, cigarette smoking, body mass index more than 25 (calculated as weight in kilograms divided by the square of height in meters), and age more than 35 years were confirmed risk factors for the development of PFDs during pregnancy and postpartum. CONCLUSION: Almost half of the women included in the study suffered from PFD-related symptoms with important consequences on quality of life. Validated questionnaires are fundamental in early diagnosis and treatment of PFDs.

Microablative Fractional CO2 Laser for Vulvovaginal Atrophy in Women With a History of Breast Cancer: A Pilot Study at 4-week Follow-up.

BACKGROUND: Breast cancer (BC) is the most common female cancer worldwide. Menopausal symptoms are a well-known side effect in women with BC and have a significant negative impact on quality of life (QoL) and sexuality. Nowadays, hormonal replacement therapy and local estrogens are the most common prescriptions to treat vulvovaginal (VVA) symptoms. However, in women with a history of BC, proper therapy for such conditions remains an often inadequately addressed clinical problem. A treatment with microablative fractional CO2 laser (MLT) can produce a remodeling of the vaginal connective tissue without causing damage to the surrounding tissue. The aim of this pilot study is to assess the efficacy and safety of MLT for treating VVA symptoms in women with a history of BC at 20-week follow-up since the first laser treatment. PATIENTS AND METHODS: Women with BC and VVA symptoms were enrolled in the study and treated with 5 laser applications (one every 4 weeks). The rate of satisfied patients at 20 weeks of follow-up was evaluated with a 5-point Likert scale. Changes of the Vaginal Health Index (VHI) after treatment was compared with baseline. Effects of the laser treatment on VVA symptoms was measured using a 10-cm visual analog scale (VAS). Changes in overall QoL were assessed with a generic QoL questionnaire: the Short Form 12 (SF-12) that we analyzed considering its physical (PCS12) and mental (MCS12) domains. Sexual function was evaluated by the Female Sexual Function Index (FSFI). RESULTS: In this prospective cohort study, we enrolled 40 women with a history of BC and who currently were or (Group 2) who had been (Group 1) on treatment with endocrine therapy for their condition. Six (15.0%) women were very satisfied, 25 (62.5%) were satisfied, 6 (15.0%) were uncertain, and 3 (7.5%) were dissatisfied with the MLT. VVA symptoms and VHI improved significantly at 20 weeks from baseline (P < .05) with no differences between the 2 groups (P > .05). In terms of QoL measured by the SF-12, the PCS12 and the MCS12 significantly improved at the 20-week follow-up. A significant improvement in total FSFI and in all domains was reported in both study groups (P < .05) with no differences between groups (P > .05). CONCLUSION: MLT was safe and effective in treating VVA symptoms in women with a history of BC, irrespective of being previously or currently on endocrine therapies.

Does the Time of Onset of Urinary Symptoms Affect Microablative Fractional CO2 Laser Efficacy in Postmenopausal Women?

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of transvaginal fractional microablative CO2 laser therapy (MLT) on urinary symptoms in postmenopausal women with genitourinary syndrome of menopause (GSM) in relation to the timing of their onset; if prior to or after menopause. Secondary, the efficacy of MLT on vulvovaginal atrophy (VVA)-related symptoms. STUDY DESIGN/MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data. Postmenopausal women affected by at least one urinary symptom (urinary frequency, urgency incontinence, stress urinary incontinence) and VVA symptom each (dryness, dyspareunia, itching, burning) were enrolled. Our population was divided into two groups in relation to the onset of urinary symptoms, prior to or after menopause. Women were treated with three CO2 MLT laser sessions, administered at a 4-week interval. For urinary symptoms evaluation, we used the following disease-specific questionnaires previously validated in Italy: the Urogenital Distress Inventory score (UDI-6) and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). For each single VVA symptom, we assessed patient's severity perception with a 10-point visual analog scale. Time points of the study were at entry (T0) and at 16 weeks since the first treatment (T1). Collected data were analyzed with the Pearson χ 2 test for categorical variables and the Wilcoxon rank-sum test (for non-normally distributed data), and statistical significance was defined with a P-value <0.05. RESULTS: Sixty-one women were enrolled in this study. Overall, at T1 MLT brought to a significant improvement in urinary symptoms (P < 0.05) in women with urinary symptoms started after the menopause (Group B), contrary to the ones with urinary symptoms started before the menopause (Group A). Specifically, urinary frequency significantly improved only in Group B (P < 0.05), while urgency incontinence, significantly reduced in both groups (P < 0.05). Stress urinary incontinence did not significantly improve in both groups (P > 0.05). Secondary, all VVA symptoms showed a statistically significant improvement (P < 0.05) at 16 weeks from baseline; no differences were registered between groups. No adverse events were recorded. CONCLUSION: This study confirms the safety and efficacy of CO2 MLT for GSM symptoms. When urinary symptoms are considered, it seems that MLT might have a higher efficacy when symptoms started after menopause, in particular when they are part of the OAB syndrome. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Can we predict the evolution of untreated first stage posterior vaginal wall prolapse in women operated for anterior or apical prolapse?

OBJECTIVE: The aim of this study was to evaluate the correlation between pre-existing conditions and worsening of Stage I untreated posterior vaginal wall prolapse (PVWP) after vaginal hysterectomy and anterior repair at 12-month follow-up. METHODS: This is a multicenter retrospective study. Women with symptomatic (vaginal bulging and low back pain) anterior and/or apical pelvic organ prolapse (POP) and I stage PVWP were enrolled. Patients were submitted to vaginal hysterectomy and native-tissue anterior vaginal wall repair. Risk factors for POP development were collected for each woman before surgery. At 12 month-follow-up after surgery, women were evaluated and divided into two groups depending on the anatomical finding of the posterior vaginal wall according to the Pelvic Organ Prolapse Quantification System: women with Persistent I stage PVWP and patients with worsened PVWP more than or equal to II stage. Difference of distribution of risk factors for POP between the two groups was evaluated. Correlation between risk factors and development of PVWP more than I stage was assessed. RESULTS: Seventy women were submitted to POP surgery. Significant difference in constipation before surgery and degree of anterior and central vaginal compartments descent was observed (p < .01) between the two groups. Constipation before surgery resulted as an independent factor in worsening of PVWP at 12-month follow-up (p value = .01; odds ratio 1.99 [1.49-2.33]). CONCLUSION: Untreated Stage I PVWP, not included in the first surgical repair, can significantly get worse in women complaining of constipation at 12-month follow-up.

Low-Temperature Dielectric Anisotropy Driven by an Antiferroelectric Mode in SrTiO_{3}.

Strontium titanate (SrTiO_{3}) is the quintessential material for oxide electronics. One of its hallmark features is the transition, driven by antiferrodistortive (AFD) lattice modes, from a cubic to a ferroelastic low-temperature phase. Here we investigate the evolution of the ferroelastic twin walls upon application of an electric field. Remarkably, we find that the dielectric anisotropy of tetragonal SrTiO_{3}, rather than the intrinsic domain wall polarity, is the main driving force for the motion of the twins. Based on a combined first-principles and Landau-theory analysis, we show that such anisotropy is dominated by a trilinear coupling between the polarization, the AFD lattice tilts, and a previously overlooked antiferroelectric (AFE) mode. We identify the latter AFE phonon with the so-called "R mode" at ∼440 cm^{-1}, which was previously detected in IR experiments, but whose microscopic nature was unknown.

Resistive Switching in All-Oxide Ferroelectric Tunnel Junctions with Ionic Interfaces.

Universal, giant and nonvolatile resistive switching is demonstrated for oxide tunnel junctions with ferroelectric PbZr0.2 Ti0.8 O3 , ferroelectric BaTiO3, and paraelectric SrTiO3 tunnel barriers. The effects are caused by reversible migration of oxygen vacancies between the tunnel barrier and bottom La2/3 Sr1/3 MnO3 electrode. The switching process, which is driven by large electric fields, is efficient down to a temperature of 5 K.