Maintenance Laser Treatment for Vaginal Looseness and Sexual Dysfunction: A Double-blinded Randomized Controlled Trial.

BACKGROUND: Vaginal looseness and decreased sensation during intercourse is prevalent in up to 30%-55% of premenopausal women. The efficacy and safety of CO2 laser have been demonstrated for these indications; however, the effect is temporary, up to 6-12 months. No studies regarding the efficacy and safety of adjuvant laser treatments have been conducted to date. AIM: To evaluate the efficacy and safety of a single maintenance CO2 laser treatment in women with vaginal looseness and a concurrent decline in sexual sensation during intercourse. METHODS: This prospective double-blinded randomized controlled trial included premenopausal women who experienced significant temporary improvement in symptoms following previous treatment with CO2 laser due to the abovementioned indications. Participants were randomized to either a single CO2 laser treatment or a single sham treatment. OUTCOMES: Treatment efficacy evaluated with the female sexual function index (FSFI) and the vaginal health index (VHI). RESULTS: Overall, 119 women were included in the study. Mean VHI and FSFI scores were significantly higher in the study group compared to the control group at three months post-treatment (17.34±1.39 vs 12.86±2.23, P = .023 and 30.93±1.79 vs 25.78±1.87, P = .044, respectively). In the study group, both VHI and FSFI returned to baseline at six months post-treatment. The median rate of sexual intercourse per month was increased in the study group at three months post-treatment (8 vs 4, P = .011), and returned to baseline at six months post-treatment. CLINICAL IMPLICATIONS: Maintenance laser treatment provides a temporary non-surgical alternative for women with vaginal looseness and associated sexual dysfunction, though treatment effect seems to be limited to less than 6 months, requiring additional maintenance sessions. STRENGTHS AND LIMITATIONS: The strengths of the current study include a randomized-sham controlled design. Furthermore, VHI was used as an objective evaluation tool, in addition to the FSFI, and assessment of the rate of sexual intercourse. The homogeneity and the relatively small sample size of the cohort is a limitation, and calls for caution in interpretation of the results, and the use of CO2 laser treatment in different age groups and populations. CONCLUSION: A single maintenance laser treatment in women who previously underwent successful treatment with laser is an effective, well-tolerated, and safe procedure for treating symptoms of vaginal looseness and sexual dysfunction, though effects are temporary. Lauterbach R, Aharoni S, Farago N, et al. Maintenance Laser Treatment for Vaginal Looseness and Sexual Dysfunction: A Double-blinded Randomized Controlled Trial. J Sex Med 2022;19:1404-1411.

The efficacy and safety of a single maintenance laser treatment for stress urinary incontinence: a double-blinded randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: To evaluate the efficacy and safety of a single carbon dioxide (CO2) laser maintenance treatment in women previously treated successfully with laser for stress urinary incontinence (SUI), who have demonstrated a decline in treatment effect. METHODS: Women aged 40-70 years who experienced temporary significant improvement in symptoms following CO2 laser treatments for SUI were randomized to either the treatment group or the sham treatment control group. Cough test results, 1-h pad weights and scores on the Urogenital Distress Inventory (UDI6), the International Consultation of Incontinence Questionnaire (ICIQ-UI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were obtained at baseline and 3 and 6 months. RESULTS: Of 183 women screened, 131 were included in the final analysis. Demographic characteristics and baseline measures in the outcome tests were similar between the groups. Statistically significant improvements were demonstrated in the study compared to the control group at 3 months post-treatment in positive cough test (44.4% vs. 79.4%, P = 0.002), mean pad weight test (2.3 g ± 1.3 vs. 5.6 ± 1.1, P < 0.001), mean UDI-6(24.7 ± 12.1 vs. 45.1 ± 13.6 SD, P = 0.004), mean ICIQ-UI (16.5 ± 4.3 vs. 10.3 + 3.8, P = 0.003) and mean PISQ-12 (21.3 ± 6.8 vs. 36.6 ± 7.5, P = 0.003). However, values at 6 months post-treatment were similar to those at baseline. CONCLUSIONS: Our results suggest that a single maintenance laser treatment for reducing symptoms of SUI is transiently effective, well tolerated and safe. This treatment modality provides alternative non-surgical therapy for women with SUI.

In Vitro Fertilization Entails a High Prevalence of Erectile and Male Sexual Dysfunction: A Prospective Case-Control Study.

PURPOSE: We evaluated the effect of in vitro fertilization (IVF) on sexual function in men, particularly for erectile dysfunction. MATERIALS AND METHODS: A prospective case-control study at a tertiary medical center. The study group comprised men of infertile couples that required IVF to conceive. The control group comprised men of couples who conceived spontaneously. The effects of IVF on sexual and erectile function were assessed based on the International Index of Erectile Function (IIEF-15) and the Self-Esteem and Relationship (SEAR) questionnaires. Participants were followed up to 1 year postpartum. RESULTS: Compared to the control group (378), for the IVF group (356), mean IIEF-15 scores were significantly lower: prior to pregnancy (31.7±4.5 vs 64.4±7.2, p <0.0001), at mid-pregnancy (37.3±5.1 vs 66.4±5.5, p <0.0001) and up to one year postpartum (42.3±4.9 vs 68.6±4.3, p <0.0001). Compared to the control group, in the IVF group, mean SEAR scores were significantly lower at these 3 respective time points (29.9±6.3 vs 66.5±8.3; 34.1±5.8 vs 66.9±7.2; and 40.9±6.7 vs 67.3±5.6; p <0.0001). At the 3 time points, for the IVF compared to the control group, the median monthly sexual intercourse rate was lower; and both the use of phosphodiesterase-5 inhibitor and psychologist/sexologist care were higher. CONCLUSIONS: The prevalence of erectile dysfunction among men participating in IVF in order to conceive is significantly higher compared to couples that conceived spontaneously, thus leading to an extremely high rate of phosphodiesterase-5 inhibitor use.

Transvaginal natural orifice transluminal endoscopic versus conventional vaginal hysterectomy with uterosacral ligament suspension for apical compartment prolapse.

OBJECTIVE: The objective of this study was to compare surgical and short-term postoperative outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) versus conventional vaginal (CV) uterosacral ligament suspension (USLS) surgery. STUDY DESIGN: A retrospective cohort study was conducted on 135 patients who underwent hysterectomy with USLS via CV (n = 70) or via vNOTES (n = 65). Patients' baseline characteristics, surgical characteristics, and surgical outcomes were retrieved. The primary outcome was total operative time. Secondary outcomes include intra- and post-operative complications. RESULTS: Salpingectomy was performed in all vNOTES procedures and in only 27 % of conventional vaginal procedures (p < 0.005). Compared to the conventional vaginal procedures (n = 65), the vNOTES (n = 70) showed lower mean operative time and mean anesthesia time (101.4 ± 22.3 vs 125.5 ± 27.6 min and 141.4 ± 29.6 vs. 174.0 ± 32.9 min, respectively); and slightly longer median hospital stay (3 [range 2-4] vs. 2 [range 2-4] days, p < 0.05). Compared to women who underwent conventional vaginal hysterectomy with USLS, women who underwent vNOTES hysterectomy with USLS had lower incidences of intraoperative complications (6% vs. 18 %, p < 0.05) and intraoperative ureteral obstruction (0% vs. 8%, p < 0.05); and less estimated blood loss (58 ± 68 ml vs. 143 ± 87 ml, p < 0.05). CONCLUSION: vNOTES hysterectomy with USLS is associated with reduced incidence of intraoperative complications, shorter surgical and anesthesia time, and slightly longer hospital stay, compared to the traditional vaginal surgical approach. Post-operative complications during hospital stay were similar and infrequent following the two procedures.

Vaginal Fractional Carbon Dioxide Laser Treatment and Changes in Vaginal Biomechanical Parameters.

BACKGROUND AND OBJECTIVES: Vaginal fractional carbon dioxide (CO2 ) laser treatment has emerged in the past two decades as a non-surgical option for vaginal tightening. Mounting evidence supports the effectiveness and safety of this treatment for female sexual dysfunction. A newly developed vaginal tactile imaging (VTI) technique accurately evaluates the biomechanical parameters of the female pelvic floor and vagina, including tissue elasticity, pelvic support, and pelvic muscle function in high definition. In the current study, we evaluated changes in objective biomechanical parameters using VTI, following vaginal CO2 laser treatment for vaginal tightening and sexual dysfunction. STUDY DESIGN/MATERIALS AND METHODS: We conducted a prospective cohort between June 2018 and January 2020. Inclusion criteria were vaginal looseness, decreased local sensation during sexual intercourse, and sexual dysfunction. All the participants were treated with a vaginal carbon dioxide laser. They underwent a gynecological evaluation based on the Vaginal Health Index (VHI) and sexual function assessment according to the Female Sexual Function Index (FSFI). Vaginal biomechanical parameters were assessed by VTI. Initial evaluations were performed at the pre-treatment consult visit, 1 week prior to the first treatment and at a 6-month post-treatment follow-up visit. RESULTS: Twenty-five women were included in the final analysis. Compared with baseline, the post-treatment mean scores for vaginal elasticity and tightening were higher (54.8 ± 5.2 vs. 41.5 ± 6.3, P = 0.0027 and 1.97 ± 0.25 vs. 1.32 ± 0.31, P = 0.0014, respectively). Post-treatment increases were demonstrated in pelvic muscle contraction strength (25.9 ± 3.5 vs. 16.5 ± 4.2, P = 0.0011) and in reflex pelvic muscle contraction (2.93 ± 0.44 vs. 2.12 ± 0.47, P = 0.0022); the mean FSFI and VHI scores were higher following treatment (28.47 ± 1.73 vs. 21.12 ± 1.58, P = 0.036 and 19.15 ± 1.27 vs. 11.6 ± 0.97, P = 0.0032). CONCLUSIONS: The quantification of vaginal biomechanical parameters using VTI technology offers objective evidence of the beneficial effect of vaginal CO2 laser treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Female Sexual Orgasmic Dysfunction and Genital Sensation Deficiency.

INTRODUCTION: Most studies on female sexual dysfunction (FSD), and female sexual orgasmic disorder (FSOD) in particular, have qualitatively examined cultural and educational factors; only few have quantitatively examined physiological factors. AIM: The aim of this study was to compare quantitative sensory testing (QST) between women for whom FSOD was their primary complaint and other women with FSD. METHODS: In this retrospective study of women who visited a sexual dysfunction clinic, the study group comprised women for whom FSOD was their primary complaint, and the control group comprised other women with FSD. Sexual dysfunction was assessed by the Female Sexual Function Index (FSFI). QST was performed with a thermal and vibration Genito-Sensory Analyzer (GSA; Medoc Ltd, Israel) aimed at the clitoral and vaginal areas. MAIN OUTCOME MEASURE: The main outcome was clitoral and vibratory sensory thresholds in accordance with the presence of FSOD. RESULTS: The study group comprised 89 (45%) women, with a mean age of 37.6 ± 1.9 years; and the control group comprised 110 (55%) women, with a mean age of 37.5 ± 11.3 years. Both mean FSFI-FSOD and total FSFI scores were significantly lower in the study group than in the control group (0.97 ± 0.94 vs 1.91 ± 1.3, P < 0.001) and (11.9 ± 3.2 vs 15.6 ± 3.6, P < 0.001), respectively. Mean clitoral vibratory sensory thresholds were higher in the study group than in the control group: 2.02 confidence interval (CI) 1.12-2.64 vs 1.55 CI 1.12-2.41, P < 0.001. No statistically significant difference was found between the groups in vaginal vibratory thresholds: 3.7 CI 2.6-6.6 vs 3.4 CI 1.9-5.4, P = 0.14. CLINICAL IMPLICATIONS: The findings support the role of the clitoris in obtaining sexual orgasm, thus inferring a possible physiologic cause of FSOD in otherwise healthy women, beyond established psychological causes. STRENGTH & LIMITATIONS: Assessments using an objective quantitative measure (QST) and a subjective tool (FSFI) in both the FSOD and control groups are strengths of this study. The retrospective design is a limitation. CONCLUSION: QST showed a direct correlation between vibratory clitoral stimulation and FSOD; Compared with the control group, women with FSOD are relatively insensitive to clitoral stimulation, but not to vaginal stimulation. Gruenwald I, Lauterbach R, Gartman I, et al. Female Sexual Orgasmic Dysfunction and Genital Sensation Deficiency. J Sex Med 2020; 17:273-278.

Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.

It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.

Urokinase-type plasminogen activator (uPA) modulates monocyte-to-macrophage differentiation and prevents Ox-LDL-induced macrophage apoptosis.

OBJECTIVE: Monocyte-to-macrophage differentiation and macrophage death play a pivotal role in atherogenesis. uPA and its receptor uPAR are expressed in atherosclerotic lesion macrophages and contribute to atherosclerosis progression. In the present study we investigated the effect and mechanisms of action of uPA on monocyte-to-macrophage differentiation and on macrophage apoptotic death. METHODS AND RESULTS: The number of mouse peritoneal macrophages (MPM) harvested from uPAR-deficient (uPAR(-/-)) mice was significantly lower by 30% in comparison to control C57BL/6 mice. In vitro, uPA intensified PMA-induced THP-1 monocyte differentiation, as determined by increased expression of the macrophage marker CD36. This effect was mediated via G1 arrest, downregulation of G2/S phase and inhibition of PMA-induced cell death. uPA attenuated MonoMac6 (MM6) macrophage-like cell line apoptosis induced by oxidized LDL (Ox-LDL) and by thapsigargin (inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPase), but not by staurosporine (protein kinase inhibitor), suggesting that uPA antiapoptotic activity is Ca(2+)-independent, but involves a kinase activation. The antiapoptotic activity of uPA was dependent on the presence of uPAR, and it involved ERK1/2 activation-dependent downregulation of the proapoptotic protein Bim in macrophages stimulated with Ox-LDL. CONCLUSIONS: The present study demonstrates, for the first time, that uPA stimulates the differentiation of monocytes into macrophages and attenuates Ox-LDL-induced macrophage apoptotic death via ERK1/2 activation-dependent Bim downregulation. These processes may result in prolonged macrophage survival in the lesion, increased lesion cellularity, and eventually necrosis, which accelerates lesion development.

Paraoxonase 1 (PON1) reduces macrophage inflammatory responses.

OBJECTIVES: Paraoxonase 1 (PON1) was suggested to play an anti-inflammatory role. In the present study we questioned whether PON1 has a direct impact on macrophage inflammatory responses, and the possible functional implications of such effects. METHODS AND RESULTS: Ex-vivo studies were performed with bone marrow-derived macrophages (BMDM) harvested from C57BL/6 and human-PON1 transgenic (PON1-Tg) mice, and for the in vitro studies the J774.A1 macrophage-like cell line was used. Pro-inflammatory (M1) activation was induced by LPS and INFγ. The spontaneous and M1-induced TNFα and IL-6 secretion were significantly reduced in BMDM derived from PON1-Tg vs. C57BL/6 mice. In vitro, PON1 dose-dependently attenuated both the spontaneous and M1-induced TNFα and IL-6 secretion, and contributed to the anti-inflammatory activity of HDL. Functionally, PON1 attenuated M1-induced production of reactive oxygen species (ROS), phagocytosis, and necrotic macrophage death. PON1 anti-inflammatory activity was mediated, at least in part, via binding to SR-BI, but was independent of the enzyme catalytic activity or of cholesterol efflux stimulation, and did not involve binding to ABCA1. CONCLUSIONS: The present study demonstrates, for the first time, that PON1 directly suppresses macrophage pro-inflammatory responses. These findings suggest that PON1 decreases sustained pro-inflammatory reactions, which subsequently can attenuate plaque progression.