Safety and efficacy of non-ablative CO2 laser treatment of vulvo-vaginal atrophy in women with history of breast cancer.

PURPOSE: Breast cancer survivors (BCS) suffer severe vulvo-vaginal atrophy (VVA) and some of the most effective therapies are contraindicated. In literature we have no data about the non-ablative CO2 laser on these women. The aim of this study was to examine its efficacy, safety and acceptability in BCS. MATERIALS AND METHODS: The enrolled women underwent 3 sessions of laser therapy (t0, t1, t2) and a one-month follow up examination (t3). At each time point we measured objective signs of VVA via VHI (Vaginal Health Index) and VuHI (Vulvar Health Index) and subjective parameters (Dryness, Burning, Itching, Dysuria) via visual analog scales (VAS). In sexually active women we evaluated the sexual function with FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) scores and MENQOL (menopause quality of life questionnaire). RESULTS: We enrolled 26 BCS. The mean VHI, VuVHI, dryness and burning VAS scores improved significantly and this improvement was not influenced by the initial VVA grade. MENQOL sexual domain, Lubrication, Orgasm and Pain domains and FSFI total score improved significantly, while Desire, Arousal and Satisfaction domains of FSFI and FSDS did not. At t0 women using Aromatase Inhibitors suffered more severe vaginal dryness than women using Tamoxifen or no therapy, but the three subgroups improved without differences. No adverse event and minimum discomfort were reported. CONCLUSIONS: The non-ablative CO2 laser is a safe and effective treatment of VVA and has positive effects on sexual function in BCS regardless the use of adjuvant therapies and the initial grade of VVA.

Dienogest alone or dienogest combined with estrogens in the treatment of ovarian endometriomas, that is the question. A retrospective cohort study.

PURPOSE: to compare the effects of Dienogest 2 mg (D) alone or combined with estrogens (D + ethinylestradiol 0.03 mg, D + EE; D + estradiol valerate 1-3 mg, D + EV) in terms of symptoms and endometriotic lesions variations. METHODS: This retrospective study included symptomatic patients in reproductive age with ultrasound diagnosis of ovarian endometriomas. Medical therapy for at least 12 months with D, D + EE or D + EV was required. Women were evaluated at baseline visit (V1) and after 6 (V2) and 12 months (V3) of therapy. RESULTS: 297 patients were enrolled (156 in the D group, 58 in the D + EE group, 83 in the D + EV group). Medical treatment leaded to a significant reduction in size of endometriomas after 12 months, with no differences between the three groups. When comparing D and D + EE/D + EV groups, a significant decrease of dysmenorrhea was detected in the D group than in D + EE/D + EV group. Conversely, the reduction of dysuria was more significative in the D + EE/D + EV groups rather than in the D group. Regarding tolerability, treatment associated side effects were reported by 16.2% patients. The most frequent one was uterine bleeding/spotting, significantly higher in the D + EV group. CONCLUSION: Dienogest alone or associated with estrogens (EE/EV) seems to be equally effective in reducing endometriotic lesions mean diameter. The reduction of dysmenorrhea was more significative when D was administered alone, while dysuria seems to improve more when D is associated with estrogens.

The COVID-19 Pandemic Impact on the Psychophysical Health of Post-Menopausal Women: A Cross-Sectional Study.

Background and Objectives: The aim of this study was to investigate lifestyle, menopausal symptoms, depression, post-traumatic stress disorder (PTSD) and sleep disorders in post-menopausal women throughout the first wave of the COVID-19 pandemic, including the impact of menopause hormonal therapy (HT). Materials and Methods: Post-menopausal women were given the following questionnaires: socio-demographic characteristics; lifestyle; history of COVID-19; menopause-specific quality of life (MENQOL), the first part of which refers to the pre-pandemic period ("pre COVID-19") and the second refers to the current period ("during COVID-19"); Beck's depression inventory (BDI); the impact of event scale-revised (IES-R); and the Pittsburgh sleep quality index (PSQI). Results: One hundred and twenty-six women completed all questionnaires, with a mean age of 55.5 ± 6.0 years. The mean menopause duration was 5.7 ± 5.6 years. Twenty-four women were taking HT. A significant mean weight gain, a reduction in physical activity (respectively p < 0.001) and worsened quality of romantic relationships (p = 0.001) were reported during the pandemic. Menopausal symptoms did not vary significantly throughout the pandemic; however, women taking menopausal HT had lower physical (p = 0.003) and sexual (p = 0.049) MENQOL domain scores, lower depressive symptoms (p = 0.039) and better romantic relationships (p = 0.008). Conclusions: The COVID-19 pandemic caused reduced physical activity, worsened food habits and weight gain in post-menopausal women. They also reported a high rate of severe-moderate PTSD and a negative influence on their romantic relationships. Menopausal HT seems to be a potential protective factor for sexual and physical status and for symptoms of depression.

Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy.

BACKGROUND: Among treatments for vulvo-vaginal atrophy (VVA), there is a new kind of energy-based device, the non-ablative CO2 laser. AIM: This study aimed to assess the efficacy and safety of the non-ablative CO2 laser in menopausal women with VVA as a monotherapy or in association with vaginal estriol or moisturizer. METHODS: Seventy-five women with VVA received laser treatment (Laser group), laser plus estriol gel (Laser+E) or laser plus moisturizers (Laser+M). The study protocol consisted of 3 monthly laser sessions (t0, t1, t2) and a gynecological examination at baseline and 1 month after last laser treatment (t3). Objective measures included VHI (Vaginal Health Index) and VuHI (Vulvar Health Index); subjective symptoms of VVA (Dryness, Burning, Itching, Dysuria) evaluated via visual analog scales, sexual function evaluated by FSFI (Female Sexual Function Index), FSDS (Female Sexual Distress Score) and MENQOL (Mopause-specific Quality Of Life). Adverse events and discomfort encountered during the procedure were also assessed. OUTCOMES: Primary outcomes were the evaluation of VHI and VuHI and secondary outcomes were changes in VVA symptoms (VAS), sexual function (MENQOL, FSFI, FSDS) and discomfort during the procedure. RESULTS: Seventy-five women (25 in Laser, 25 in Laser+E and 25 in Laser+M group) completed the study. At t3, mean VHI, VuHI, dryness, burning and itching VAS scores improved significantly with no differences between the groups. The lubrication domain of FSFI improved significantly only in the Laser+M group, while the pain domain improved significantly in all women with no differences between the groups. FSFI and FSDS overall scores and MENQOL sexual domain improved in all women with no significant difference between the groups. The mean score of the pain during the procedure was low at t0 and did not change throughout the study. CLINICAL IMPLICATIONS: This study extends knowledge concerning the effectiveness of a new non-ablative CO2 laser in post-menopausal women with VVA. STRENGTHS & LIMITATIONS: This is one of the first studies on this kind of laser and is the first to compare the effectiveness of laser treatment alone or in combination with vaginal estriol or moisturizers. Parameters of VVA and sexual function were evaluated using validated tools. Study limitations include short follow-up time, the limited number of participants and the absence of a sham-controlled group. CONCLUSION: Non-ablative CO2 laser seems to be an effective treatment for VVA in menopausal women. Our preliminary data shows that it can be effective as monotherapy or with adjuvant treatments. Alvisi S, Lami A, Baldassarre M, et al. Short-Term Efficacy and Safety of Non-Ablative Laser Treatment Alone or with Estriol or Moisturizers in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med 2022;19:761-770.

Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey.

BACKGROUND: Transgender people are a vulnerable group with a higher incidence of mental health issues and, during the COVID-19 outbreak, they may have faced psychological, physical and social obstacles. AIM: To evaluate the impact of the pandemic and the access to health care services during the COVID-19 pandemic on the mental health of the transgender people living in Italy. METHODS: An anonymous web-based survey was conducted among transgender people living in Italy. OUTCOMES: The survey consisted of 41 questions (to address socio-demographic and COVID-19 related variables, general health problems and trans-related health issues) and three validated questionnaires (the Impact of Event Scale [IES], the Beck Depression Inventory [BDI-II] and the SF-12. RESULTS: In total 108 respondents were included in the analysis, of these 73.1% were transmen and 26.9% transwomen. The mean age was 34.3 ± 11.7 years with 88.9% undergoing gender affirming hormonal treatment (GAHT). Of these respondents 55.6% were not working during the COVID-19 pandemic, mainly because they lost their jobs due to the lockdown (30.5%) or because they were otherwise unemployed (25.0%). Only four subjects were quarantined at home because of a positive COVID-19 swab. The mean total IES score was 21.1 ± 14.9 with 24.1% of subjects scoring over the cut-off score of 26 thereby suggesting a moderate-to-severe impact of the pandemic event. Mean BDI score was 8.6 ± 8.4. SF-12 total mean score was 96.1 ± 11.9 with a Mental Component Summary (MCS) score of 42.8 ± 9.1. Access to endocrinological consultations for hormonal prescription via telemedicine services was associated with better IES total scores (P = .01). CLINICAL IMPLICATIONS: Our results highlight the impact of the pandemic on the mental health of this particular population and how telemedicine services may serve to mitigate negative psychological effects. STRENGTHS & LIMITATIONS: Internet-based surveys may select a group of people not necessary representative of the whole population. The self-reporting bias should also be considered. Those who responded to our survey were mainly from northern Italy were COVID-19 has had a greater impact. CONCLUSION: Vulnerable groups such as the transgender population should receive more consideration also during pandemic events and their access to health services especially for endocrine and mental health care should be improved. A nationwide plan for the extended use of telemedicine should be established with targeted intervention to reduce psychological distress. Gava G, Fisher AD, Alvisi S, et al. Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey. J Sex Med 2021;18:900-907.

A Randomized Double-Blind Placebo-Controlled Pilot Trial on the Effects of Testosterone Undecanoate Plus Dutasteride or Placebo on Muscle Strength, Body Composition, and Metabolic Profile in Transmen.

BACKGROUND: While the effects of androgens on muscle are well described in hypogonadal men, literature is still scarce on muscular strength or size variations in transmen; in this population there are no data regarding the relative effect of testosterone (T) and its metabolite dihydrotestosterone on muscle. AIM: Our primary objective was to compare the effects on muscle strength of 54-week administration of testosterone undecanoate (TU) combined with the 5α-reductase inhibitor dutasteride (DT) or placebo (PL). Secondary outcomes included evaluation of body composition, bone, cutaneous androgenic effects, and metabolic variations. METHODS: In this randomized, double-blind PL-controlled pilot trial, 16 ovariectomized transmen were randomized to receive TU 1,000 mg IM at week 0, 6, 18, 30, 42 plus a PL pill orally daily (TU + PL, n = 7) or plus DT 5 mg/d (TU + DT, n = 7). OUTCOMES: At week 0 and 54 the following parameters were evaluated: isokinetic knee extension and flexion peak torque and handgrip strength, body composition, and bone mineral density, biochemical, hematological, and hormonal parameters. RESULTS: Handgrip and lower limb strength increased significantly in both groups with no differences between the 2 groups. Fat mass decreased and lean mass increased significantly similarly in both groups. Metabolic parameters remained stable in the 2 groups except for high-density lipoprotein cholesterol that was reduced in both groups. Hepatic and renal function remained normal in both groups and no major adverse effects were registered in either group. CLINICAL IMPLICATIONS: These results may be particularly relevant for transmen experiencing cutaneous androgenic adverse events such as acne and androgenetic alopecia and in light of the development of non-5α-reduced androgens. STRENGTHS & LIMITATIONS: The strength of this study was the randomized, double-blind PL-controlled design, while the small number of subjects was definitely the biggest limitation. CONCLUSION: For the first time we demonstrated that the addition of DT does not impair the anabolic effects of T on muscles in transmen previously exposed to T, supporting the hypothesis that the conversion in dihydrotestosterone is not essential for this role. Gava G, Armillotta F, Pillastrini P, et al. A Randomized Double-Blind Placebo-Controlled Pilot Trial on the Effects of Testosterone Undecanoate Plus Dutasteride or Placebo on Muscle Strength, Body Composition, and Metabolic Profile in Transmen. J Sex Med 2021;18:646-655.

Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals.

BACKGROUND: Over the last few years, the gender binary has been questioned, highlighting the existence of gender diverse people, who identify as neither (exclusively) male nor female. AIM: The present study evaluated the possible differences in terms of psychological wellbeing between binary and gender diverse individuals, as well as the role of perceived social acceptance and religious fundamentalism as possible mediators of psychopathology in gender diverse people. Furthermore, the diversity of gender-affirming hormonal treatment requests according to gender identification was investigated. METHODS: A sample of 563 transgender people aged 18-70 was enrolled (n = 264 assigned female at birth, AFAB and n = 299 assigned male at birth, AMAB), all individuals referring to several Italian gender clinics. A subdivision of the study population based on the gender identity visual analog scale (GI-VAS) median was performed, in order to distinguish between gender diverse and binary transgender individuals. Moreover, a linear regression analysis was performed entering logarithmically transformed GI-VAS (Log GI-VAS) into the models with psychometric scales. OUTCOMES: Psychometric and sociodemographic data, as well as information regarding requests for gender-affirming treatments, were extrapolated from the clinical interviews conducted during the first referral. RESULTS: Gender diverse individuals showed significantly less intense gender dysphoria and higher levels of depression and anxiety compared to binary ones; accordingly, a less binary gender identity correlated with higher levels of depression and anxiety and lower levels of gender dysphoria. The depressive symptomatology in gender diverse people was partially mediated by perceived discrimination and humiliation. Moreover, gender diverse AMAB people sought a non-standard hormonal treatment more often than their binary counterpart. CLINICAL IMPLICATIONS: The present study highlights the importance for transgender health professionals, when planning gender-affirming hormonal treatments, to offer flexible interventions, tailored on the patient's needs and goals. STRENGTHS & LIMITATIONS: Strengths included exploring whether and how perceived discrimination may affect mental health in gender diverse people. Limitations included the enrolled sample of people referring to different gender clinics, which is not fully representative of the transgender population. CONCLUSION: This study highlights the importance of evaluating each individual's unique health care needs, exploring each single request and its underlying reasons. Romani A., Mazzoli F., Ristori J., et al. Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals. J Sex Med 2021;18:1933-1944.

The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women.

BACKGROUND: Vulvo-Vaginal Atrophy (VVA) affects about fifty percent of postmenopausal women, contributing more vulnerable sexual and psycho-relational equilibrium. To date, no psychometric instruments have been designed to assess the impact of coital pain associated with VVA on sexual quality of life. AIM: To validate a new psychometric tool, the Gynogram, able to investigate coital pain and to quantify its impact on sexual well-being in menopause. METHODS: 214 sexually active postmenopausal women were enrolled in the study during clinical consultations in gynecological outpatient clinics in Italy. After gynecological examination and evaluation of the presence of VVA, the study sample was divided in a clinical group (103 women with certified diagnosis of VVA) and in a control group (111 women without certified diagnosis of VVA) according to the Vaginal Health Index (VHI) cut-off. Factor, Reliability and Receiving Operating Characteristics (ROC) analysis were performed in order to validate our newly created Gynogram. OUTCOMES: A structured questionnaire, named Gynogram, to assess coital pain and its impact, and the Female Sexual Function Index (FSFI). RESULTS: The factor analysis performed on the original form (80 items) reduced the Gynogram to 24 items. Reliability analysis conducted with Cronbach's Alpha coefficients showed high values in all the components (ranging from .813 to .972), both in the long and in the short form. The sensitivity analysis demonstrated that the Gynogram, with a cut-off ≤93, is able to recognize a clinically significant coital pain. With respect to the FSFI, statistically significant differences were found for all the domains. In addition, statistically significant differences were found for all the twelve factors of the Gynogram, showing that VVA profoundly affects the sexual quality of life of women in post-menopause. CLINICAL TRANSLATION: The utility of this tool consists in the possibility to improve prognosis, compliance/adherence and treatment outcomes. STRENGTHS AND LIMITATIONS: The Gynogram is able to evaluate and to quantify the impact of coital pain associated with VVA. Moreover, it can also recognize the areas of biopsychosocial functioning being more affected by this clinical condition. The main limit of the study is the impossibility to evaluate both mental health and partner's general and sexual health. CONCLUSIONS: The Gynogram is a new and validated psychometric tool able to detect the impact of symptomatic VVA on sexual quality of life among post-menopausal women, with a specific focus on the different areas of sexual functioning. Nappi RE, Graziottin A, Mollaioli A, et al. The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women. J Sex Med 2021;18:955-965.

Completeness of exercise reporting among randomized controlled trials on pelvic floor muscle training for women with pelvic organ prolapse: A systematic review.

AIMS: This systematic review aimed to assess the completeness of exercise reporting in randomized controlled trials (RCTs) on pelvic floor muscle training (PFMT) for women with pelvic organ prolapse (POP). METHODS: MEDLINE, Cochrane Central, CINHAL, Embase, SCOPUS, and PEDro databases were searched up to October 2020. Full-text RCTs comparing PFMT to any type of intervention among women with any type and stage of POP were eligible for inclusion. Completeness of intervention was evaluated with t20he template for intervention description and replication (TIDieR) and the consensus on exercise reporting template (CERT). Inter-rater agreement for each item of the tools was calculated. RESULTS: Twenty-six RCTs were included. None of the studies completely reported all intervention descriptors. On average 57.1% (6.8 ± 2.4; out of 12) of the overall TIDieR items and 35.3% (6.7 ± 2.9; out of 19) of the CERT were well described. In particular, 7 and 5 items were completely reported more than 50% of the time for the TIDieR and CERT, respectively. Frequent shortcomings were the undetailed reporting of information regarding tailoring and modifications of exercises and their adherence. Detailed descriptions of exercise repetitions to enable replication were missing in 53.8%. According to the CERT, only 11.5% of the RCTs sufficiently described the main providers' characteristics. CONCLUSION: The completeness of PFMT reporting for women with POP is still below desirable standards and it is insufficient to ensure transferability into practice. The present results may add relevant knowledge and contribute to improving adequate reporting of exercise.

Complete Androgen Insensitivity Syndrome: From Bench to Bed.

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.

Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data.

INTRODUCTION: As far as we know, no studies to date have investigated the psychobiological correlates of sexual distress (SD) nor the impact of hormonal treatment (HT) on SD in transgender persons. AIM: To evaluate the psychobiological correlates of SD and assess the effects of HT on SD in transgender persons without gender-affirming surgery. METHODS: A consecutive series of 301 transgender persons (160 transwomen and 141 transmen) was considered for the cross-sectional study, and a subset of 72 subjects was studied in a 2-year follow-up. A physical examination was performed. Blood samples were drawn for determination of cortisol levels. Subjects completed psychometric measures. During 2 years of HT, the evaluation of SD was prospectively repeated. MAIN OUTCOME MEASURE: Psychobiological correlates of SD in transgender population. Changes in SD during gender affirming hormonal treatment. CLINICAL IMPLICATIONS: Knowing how hormonal treatment influence SD will help care providers when counseling transgender people. STRENGTHS & LIMITATIONS: To the authors' knowledge, this is the first study prospectively evaluating the impact of gender affirming hormonal treatment on sexual distress in transgender individuals. The main limitations are represented by the small size of the sample and the use of questionnaires validated only in the cisgender population. RESULTS: SD showed a positive correlation with body uneasiness (P < .0001) and with dissatisfaction toward gender-related body parts or shapes (all P < .05). In addition, SD correlated positively with general psychopathology (P < .0001), alexithymia, social anxiety, and humiliation scales (all P < .05). In transmen, SD was positively associated with autism levels (P < .005), as well as with cortisol levels (P < .02). A significant correlation between SD and perceived discrimination was observed in transwomen (P < .05). In transwomen, SD was positively associated with hair density and negatively with breast growth (both P < .05). Finally, in transmen, a negative correlation was found between SD and hair density (P < .05). When the impact of HT on SD was evaluated, a significant reduction of SD was observed across time in both transwomen and transmen (P = .001 and P = .01, respectively). CONCLUSIONS: The present results support the efficacy of HT in reducing SD in transgender persons. Ristori J, Cocchetti C, Castellini G, et al. Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data. J Sex Med 2020;17:142-151.

Transvaginal Ultrasound and Doppler Features of Intraligamental Myomas.

OBJECTIVES: To describe the ultrasound (US) features of intraligamental myomas (IMs) using Morphological Uterus Sonographic Assessment group standardized terminology. METHODS: This was a retrospective monocentric study. A total of 125 consecutive women with a preoperative US diagnosis of a myoma located close to the uterine isthmus (International Federation of Gynecology and Obstetrics stages 5, 6, and 7) from 2016 to 2019 who underwent laparoscopic or laparotomic myomectomy or hysterectomy were included for study analyses. The US data were retrieved from US reports and stored digital images by 2 authors. Ultrasound features of myomas were described according to Morphological Uterus Sonographic Assessment terminology. Clinical data for the study population were retrieved from the patients' records. RESULTS: Nineteen women with a surgical confirmation of an IM were included in the study group; the remaining population constituted the control group (n = 106). Non-uniform echogenicity was detected in 17 of 19 (89%) of IMs compared to 26 of 106 (25%) fibroids in the control group (P < .001). The presence of shadowing was detected in 12 of 19 (63%) IMs compared to 94 of 106 (89%) cases in the control group (P = .004). Intraligamental myomas were more vascularized tumors compared to myomas in the control group (P = .004). Transvaginal US showed high specificity for the diagnosis of an IM (0.93; 95% confidence interval, 0.87-0.96). CONCLUSIONS: On US imaging, IMs appear as vascularized solid tumors with nonuniform echogenicity; cones of shadows were less frequent in IMs than the control group, and this finding can help in the differential diagnosis. Knowledge of their specific US features could help sonographers make an accurate diagnosis, allowing them to plan correct surgery and avoid severe complications.

Adenomyosis and endometriosis in adolescents and young women with pelvic pain: prevalence and risk factors.

AIM: To evaluate the prevalence of ultrasound diagnosis of adenomyosis and endometriosis in young women complaining of pelvic pain and to find the symptoms and clinical characteristics associated with these diseases in young women. METHODS: Cross-sectional study, including 100 young women (14-24 years) with a history of chronic pelvic pain. Women were asked detailed medical hystory and pain symptoms scores (Visual Analogue Scale) and underwent gynecological examination and ultrasound evaluation. RESULTS: The prevalence of endometriosis and adenomyosis in young women amounted to 25.0% and 46.0%, respectively. A significant correlation was found between ovarian endometriosis and adenomyosis. Dysmenorrhea and dyspareunia were risk factors for adenomyosis. Dyschezia, dyspareunia, chronic pelvic pain, presence of sonographic soft markers suggestive of pelvic adhesions, being a worker and having a previous surgery were risk factors for endometriosis. Young women (20-24 years) had a higher incidence of both adenomyosis and endometriosis than adolescents (14-19 years). CONCLUSIONS: Our outcomes strengthen the hypothesis of a progressive and common course of the natural history of endometriosis, which initially may manifest with symptoms, then with signs of pelvic adhesions and finally as adenomyosis, ovarian endometriomas or deep infiltrating endometriosis.

Prevalence and Psychopathological Determinants of Sexual Dysfunction and Related Distress in Women With and Without Multiple Sclerosis.

INTRODUCTION: Sexual dysfunction (SD) is common but still underdiagnosed in women with multiple sclerosis (MS); in fact, the lack of a consistent use of validated diagnostic tools makes the prevalence of SD and related distress difficult to define precisely. AIM: To assess the prevalence of SD in Italian women with MS compared with age-matched healthy control subjects (HC) and the association with demographic, psychological, and MS-related characteristics. METHODS: The Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale were administered to 153 women with MS and 153 HC. Demographic, gynecologic, and neurologic data were obtained. Disability was assessed using the Expanded Disability Status Scale. Psychological symptoms were evaluated in MS patients with Profile of Mood State and the Beck Depression Inventory II. MAIN OUTCOMES MEASURES: Prevalence of SD and sexual distress in women with MS compared with HC. RESULTS: Among women sexually active in the last month, we found an increased prevalence of SD in MS patients compared with HC subjects (42.0% vs 16.0%, P = .0001). The prevalence of dysfunctional FSFI global scores (<26.55) was higher in women with MS compared with HC (49.6% vs 33.6%, P = .014). In the MS group, the prevalence of SD was similar between pre- and post-menopausal women. Both premenopausal and postmenopausal MS women presented a greater prevalence of SD if compared with the premenopausal and postmenopausal HC groups (30/79 [37.9%] vs. 5/74 [6.8%], P = .0001 and 20/40 [50.0%] vs 16/57 [28.1%], P = .03, respectively). A negative correlation was observed between the FSFI global score and age and Expanded Disability Status Scale. Depressive symptoms were more common in women with MS and SD than in those without. CLINICAL IMPLICATIONS: This study suggests that sexual function investigation should always be a standard part of the consultation with healthcare professionals for MS. STRENGTH & LIMITATIONS: The strength of this study was the comparison with an age-matched healthy control group and the use of validated questionnaires to assess both sexual function and sexual distress. Larger and multicenter studies may further support our findings. CONCLUSION: In our cohort, the prevalence of SD and sexual distress was higher in women with MS compared to the HC group. Age, disability, and depressive symptoms were associated with increased SD. Gava G, Visconti M, Salvi F, et al. Prevalence and Psychopathological Determinants of Sexual Dysfunction and Related Distress in Women With and Without Multiple Sclerosis. J Sex Med 2019;16:833-842.

Prevalence of metabolic syndrome and its components in women with and without pelvic organ prolapse and its association with prolapse severity according to the Pelvic Organ Prolapse Quantification system.

INTRODUCTION AND HYPOTHESIS: Data regarding possible associations between metabolic syndrome (MS) and pelvic organ prolapse (POP) are scarce. The primary hypothesis was that the prevalence of MS and its components was higher in postmenopausal women with POP than in age-matched women without POP staged with the Pelvic Organ Prolapse Quantification system (POP-Q). The secondary aim of the study was to analyze the association between MS and its components with POP severity. METHODS: Presence of MS and its components [elevated triglycerides (TG), waist circumference, blood pressure, and fasting glucose (FG) and decreased high-density lipoprotein cholesterol (HDL-C)] were assessed in 122 women with POP (POP-Q stage I-IV) and 77 without (POP-Q 0). Fasting insulin resistance [homeostasis model assessment for fasting insulin resistance (HOMA-IR)] was also assessed. RESULTS: TG levels, FG, and HOMA index were significantly higher in POP-Q stage I-IV compared with POP-Q 0 (p = 0.04, p = 0.0005 and p = 0.04); HDL-C was significantly reduced in POP-Q stage I-IV compared with POP-Q 0 (p = 0.0003). TG levels (p = 0.0315) were significantly higher in POP-Q stage III and IV vs. POP-Q 0; FG and HOMA-IR (p = 0.0015 and p = 0.0204) were significantly higher in POP-Q stage IV vs. POP-Q 0; HDL-C (p = 0.0047) was significantly lower in all stages vs. POP-Q 0. The prevalence of MS was different between groups (p = 0.04) and higher in POP-Q IV. Elevated TG [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.5-9.3, p = 0.004] and reduced HDL-C (OR 2.0, 95% CI 1.1-3.7, p = 0.0241) significantly increased the risk of POP-Q stage ≥III. CONCLUSIONS: MS and its components may be associated with POP. Elevated TG and reduced HDL-C are associated with POP severity.

Vaginal Health in Menopausal Women.

The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman's quality of life. Epidemiology, signs, symptoms, diagnostic criteria of VVA and target treatments for restoring vaginal health are discussed in light of the most recent literature. Issues related to this condition in menopausal women are under-diagnosed, lack objective diagnostic criteria, and consequently under-treated. Over the years, many treatments have been developed but their long-term effectiveness and safety have yet to be clearly defined. Patients are often dissatisfied and stop treatment, suggesting the need for a more personalized and tailored approach to achieve better compliance and thereby effectiveness. The aim of this paper is to provide an overview of the most recent literature on VVA in order to help the gynecologist in the management of this condition.

Cognition, Mood and Sleep in Menopausal Transition: The Role of Menopause Hormone Therapy.

During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a physiologic deterioration of hypothalamic-pituitary-ovarian axis function associated with fluctuating hormone levels. During this transition, women can suffer symptoms related to menopause (such as hot flushes, sleep disturbance, mood changes, memory complaints and vaginal dryness). Neurological symptoms such as sleep disturbance, "brain fog" and mood changes are a major complaint of women transitioning menopause, with a significant impact on their quality of life, productivity and physical health. In this paper, we consider the associations between menopausal stage and/or hormone levels and sleep problems, mood and reduced cognitive performance. The role of estrogen and menopause hormone therapy (MHT) in cognitive function, sleep and mood are also discussed.

The Impact of Hormonal Replacement Treatment in Postmenopausal Women with Uterine Fibroids: A State-of-the-Art Review of the Literature.

Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.

Hormonal Replacement Therapy in Menopausal Women with History of Endometriosis: A Review of Literature.

Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. Nevertheless, it affects up to 2.2% of postmenopausal women. Conclusive data are not available in the literature on the appropriateness of HRT in women with endometriosis or a past history of the disease. The hypothesis that exogenous estrogen stimulation could reactivate endometriotic foci has been proposed. The aim of this state-of-the-art review was to revise the current literature about endometriosis in perimenopause and menopause and to investigate the possible role of HRT in this setting of patients. An electronic databases search (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) was performed, with the date range of from each database's inception until May 2019. All of the studies evaluating the impact of different HRT regimens in patients with a history of endometriosis were selected. 45 articles were found: one Cochrane systematic review, one systematic review, five narrative reviews, two clinical trials, two retrospective cohort studies, 34 case reports and case series. Some authors reported an increased risk of malignant transformation of endometriomas after menopause in patients assuming HRT with unopposed estrogen. Low-quality evidence suggests that HRT can be prescribed to symptomatic women with a history of endometriosis, especially in young patients with premature menopause. Continuous or cyclic combined preparations or tibolone are the best choices. HRT improves quality of life in symptomatic post-menopausal women, who should not be denied the replacement therapy only due to their history of endometriosis. Based on low-grade literature evidence, we recommend to prescribe combined HRT schemes; tibolone could be considered.

Structure of Epithelial and Stromal Compartments of Vulvar and Vaginal Tissue From Women With Vulvo-Vaginal Atrophy Taking Ospemifene.

INTRODUCTION: Vulvo-vaginal atrophy affects the daily lives of most post-menopausal women. We know that ospemifene intake can induce vaginal epithelial improvements within a few weeks; however, direct evidence of the effects of ospemifene on the human vulva and on connective tissue of both the vagina and vulva are lacking. AIM: To evaluate the changes induced by ospemifene on epithelium thickness, glycogen content proliferation index, collagen content, and type I/III collagen ratio in vulvar and vaginal tissue of post-menopausal women. METHODS: 20 women who attended our gynecologic clinic for planned surgery were recruited for the study. 11 subjects were taking ospemifene at the time of inclusion, and 9 subjects who were not taking ospemifene were selected as control group. Vaginal and vulvar biopsies were taken during surgery. Histological features and glycogen content were evaluated by standard hematoxylin-eosin and periodic acid-Schiff staining, total collagen and collagen type I/III ratio were evaluated by hydroxyproline assay and Sirius red staining, while the expression of Ki67 was evaluated by immunohistochemistry. MAIN OUTCOME MEASURE: We analyzed histological features of the epithelial and stromal layer of the vaginal and vulvar vestibule mucosa. RESULTS: Vaginal and vulvar biopsies from women taking ospemifene showed an increased epithelium thickness, glycogen content, and proliferation index compared with the control group. Collagen content was also higher in women taking ospemifene, while an increased ratio between type I and III collagen fibers was found only at vaginal level. CLINICAL IMPLICATIONS: Our study shows that the effectiveness of ospemifene on vaginal tissue also extends to the vulvar vestibule. STRENGTH & LIMITATIONS: This study provides direct evidence of the impact of ospemifene on vaginal and vulvar tissue. A specifically designed longitudinal study may further support our findings. CONCLUSION: Ospemifene intake is associated with a marked improvement of various morphological and physiological features of both vaginal and vulvar vestibule epithelium, including the collagen content of the tissues. Alvisi S, Baldassarre M, Gava G, et al. Structure of Epithelial and Stromal Compartments of Vulvar and Vaginal Tissue From Women With Vulvo-Vaginal Atrophy Taking Ospemifene. J Sex Med 2018;15:1776-1784.