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Objectives: Vasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products., Study Design: Secondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February-October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products., Main Outcome Measures: Patient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment., Results: Overall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms., Conclusions: Despite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population., Competing Interests: Declaration of competing interest S.K. is an employee of University Hospitals Cleveland Medical Center and has received consulting fees or honoraria from: Astellas, Alloy, Bayer, Daré, Freya, Reunion Neuroscience, Materna Medical, Madorra, Ms. Medicine, Palatin Technologies, Pfizer, Sprout, Strategic Science Technologies, and TherapeuticsMD; and stock options from Reunion Neuroscience, Alloy, and Materna Medical. N.S., C.M., and S.S. are employees of Bayer AG, Germany. C.C. and C.J. are employees of Bayer Consumer Care, Switzerland. M.S. and M.H. are employees of Adelphi Real World, UK. L.H. is an employee of Bayer US. V.B. was an employee of Bayer, UK at the time of the study. Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Palatin Technologies, Pfizer Inc., Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationships with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck & Co, Novo Nordisk, Organon & Co, Shionogi Limited, Theramex, and Viatris., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The shift in paradigm from the belief that endometriosis exclusively affects women of reproductive age has brought attention to its manifestation in postmenopausal patients. Despite this emerging awareness, there remains a dearth of information in the literature regarding postmenopausal endometriosis, with uncertainties surrounding its prevalence, clinical significance, optimal management strategies, and prognosis. Clinical manifestations of endometriosis in menopausal patients lack specificity, with pain onset possible at any stage of life. The primary approach for symptomatic postmenopausal endometriosis continues to be surgical excision, serving both diagnostic and therapeutic purposes while mitigating the risk of coexisting malignancies. Managing the disease in postmenopausal women presents challenges due to possible contraindications for menopausal hormone therapy and the elevated risk of recurrence and malignant transformation. However, conclusive data regarding the appropriateness of menopausal hormone therapy in women with endometriosis or a history of the disease are lacking. Current recommendations lean towards prioritizing combined menopausal hormone therapy formulations or tibolone over estrogen-only therapies due to their potentially higher malignancy risk. The possible increased risk of osteoporosis and cardiovascular disease in postmenopausal women with endometriosis is likely linked to a history of surgical menopause at an earlier age, but more research is warranted. This narrative review summarizes the available literature and provides insights into the intricate connection between endometriosis and menopause, shedding light on pathogenesis, symptoms, oncologic risk, diagnosis, and treatment., Competing Interests: Declaration of competing interest Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Exeltis, HRA Pharma, Palatin Technologies, Pfizer Inc., Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Fidia, Gedeon Richter, Merck Sharpe & Dohme, Novo Nordisk, Organon & Co, Shionogi Limited, Theramex, Viatris, and Vichy Laboratories. None of these are relevant to the present work. All the other authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Genitourinary syndrome of menopause is a comprehensive term that groups genital, urinary and sexual signs and symptoms mainly due sex hormone deficiency and aging, with a crucial impact on quality of life of midlife women. While this broad definition captures the common underlying physiopathology and the frequent overlap of symptomatology, improving knowledge about different components of genitourinary syndrome of menopause may be relevant for individualized treatment, with possible implications for efficacy, compliance and satisfaction. This narrative review focuses on the vulvar component of genitourinary syndrome of menopause, highlighting anatomical and functional peculiarities of the vulva that are responsible for some of the self-reported symptoms, as well as specific signs at physical examination. Increasing evidence points towards a pivotal role of vulvar vestibular health in the occurrence of sexual pain, one of the most common and distressing symptoms of genitourinary syndrome of menopause, which should be evaluated with validated scales taking a biopsychosocial perspective. This is an essential step in the recognition of different phenotypes of genitourinary syndrome of menopause and in the assessment of the most effective diagnostic and therapeutic algorithm. Menopausal vulvar health deserves more research into tailored non-hormonal and hormonal treatment options., Competing Interests: Declaration of competing interest Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, HRA Pharma, Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter Merck Sharpe & Dohme, Novo Nordisk, Palatin Technologies, Pfizer Inc., Shionogi Limited, Theramex, and Viatris. None of these are relevant to the present work. All the other authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To analyse the effect of fezolinetant on patient-reported sleep disturbance and impairment in individuals with vasomotor symptoms (VMS) using pooled data from the SKYLIGHT 1 and 2 studies., Study Design: The SKYLIGHT studies were phase-3, double-blind investigations. Individuals (≥40-≤65 years) who were assigned female at birth and seeking treatment of/relief from moderate-to-severe VMS were enrolled. Participants were randomised to receive placebo, fezolinetant 30 mg, or fezolinetant 45 mg during a 12-week treatment period., Main Outcome Measures: Sleep assessments: Patient-Reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b), PROMIS Sleep-Related Impairment - Short Form 8a (PROMIS SRI SF 8a), and Patient Global Impression of Change/Severity in SD (PGI-C SD and PGI-S SD). Assessments were completed at baseline (except PGI-C SD), weeks 4 and 12., Results: Overall, 1022 individuals were randomised and took ≥1 dose of study drug. PROMIS SD SF 8b results showed that improvements in sleep disturbance were observed for fezolinetant 30 and 45 mg versus placebo (week 12, least squares [LS] mean differences: -0.6 [95 % confidence interval [CI]: -1.7, 0.4] for 30 mg and -1.5 [-2.5, -0.5] for 45 mg). Similar improvements in sleep impairment were reported using the PROMIS SRI SF 8a (week 12, LS mean differences: -1.1 [95 % CI: -2.1, -0.1] for 30 mg and -1.3 [-2.3, -0.3] for 45 mg). For PGI-C SD at week 12, 33.6 % (98/292 participants) of the placebo group felt much/moderately better versus 40.1 % (110/274) and 51.0 % (154/302) of the fezolinetant 30 mg and 45 mg groups, respectively. For PGI-S SD at week 12, 44.0 % (129/293) of the placebo group had severe/moderate problems versus 41.1 % (113/275) and 36.6 % (111/303) of the fezolinetant 30 mg and 45 mg groups, respectively. The 12-week timeframe for this analysis was limited by the length of the placebo-controlled period., Conclusions: Fezolinetant had a beneficial effect on four measures of sleep disturbance and impairment following treatment for VMS., Competing Interests: Declaration of competing interest Marla Shapiro C.M. has attended advisory boards and/or received consulting fees or honoraria from Aspen, Astellas, Bayer HealthCare, BioSyent, Duchesnay, GSK, Merck, Mithra, Pfizer, Searchlight, Sprout, Sunovion, and Therapeutics MD; and fulfils a leadership or fiduciary role for the International Menopause Society, Research Canada, and Terry Fox Research Institute. Antonio Cano was the past President of the European Menopause and Andropause Society; and is a consultant for Astellas, Theramex, and Viatris. Rossella E. Nappi has past financial relationships (lecturer, member of advisory boards, and/or consultant) with Boehringer Ingelheim, Eli Lilly, Endoceutics, Exeltis, Novo Nordisk, Palatin Technologies, Pfizer, Procter & Gamble, Teva Women's Health, and Zambon; has ongoing relationships with Abbott, Astellas, Bayer HealthCare, Fidia, Gedeon Richter, HRA Pharma, Merck & Co, Organon, Shionogi, and Theramex; and serves as President Elect of the International Menopause Society. Nanette Santoro is a study investigator, member of a scientific advisory board, and consultant for Astellas; a member of a scientific advisory board for Amazon (Project Ember), MenoGeniX, and QUE Oncology; a consultant for Ansh Labs; an Associate Editor for Menopause; and a past President of the Society for Reproductive Investigation. Marci L. English, Shayna Mancuso, Udaya Valluri, and Faith D. Ottery are employees, or former employees, of Astellas Pharma Inc. Antonia Morga and Emad Siddiqui are employees of Astellas Pharma Europe Ltd., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Despite the profound impact of menopausal symptoms on women, treatment utilization is low, and many seek alternative therapies. The REALISE study aimed to evaluate the treatment landscape - that is, pharmacological treatment, lifestyle changes (LC), and use of over-the-counter (OTC) products - for women from six high-income countries experiencing vasomotor symptoms (VMS) and receiving healthcare., Study Design: Analysis of a secondary dataset, the Adelphi Real World Disease Specific Programme™, a large, cross-sectional, point-in-time survey conducted in the United States and five European countries (February-October 2020). Physicians provided demographic, clinical, and treatment data; women were stratified by VMS severity (mild; moderate-severe) and presence of concomitant sleep/mood symptoms. Women completed forms on VMS severity, concomitant symptoms, LC, and OTC product use. Two subgroups were identified: VMS-only and VMS + sleep/mood., Main Outcome Measures: Prescription treatment, LC, and OTC product utilization., Results: Physicians (n = 233) provided data on 1767 women; 825 (46.7 %) completed a self-completion form. Physicians rated 60 % of women with moderate-severe VMS, of whom 709 (66.8 %) were currently prescribed pharmacological treatment; 27.1 % had never been prescribed. Hormone therapy was most frequently prescribed in the moderate-severe group (overall, 49.8 %; VMS-only, 57.4 %; VMS + sleep/mood, 47.3 %), followed by serotonergic antidepressants (15.7 %; 9.7 %; 17.6 %, respectively). Most women (78.3 %) with moderate-severe VMS adopted LC, and 57.6 % used at least one OTC product for VMS relief., Conclusions: Nearly a third of women with moderate-severe VMS had never received treatment despite access to healthcare. This, combined with the prevalent use of LC/OTC products, suggests an unmet need for new treatment options to manage VMS and concomitant sleep/mood symptoms., Competing Interests: Declaration of competing interest S.K. is an employee of University Hospitals Cleveland Medical Center and has received consulting fees or honoraria from: Astellas, Alloy, Bayer, Daré, Freya, Reunion Neuroscience, Materna Medical, Madorra, Ms. Medicine, Mithra, Palatin Technologies, Pfizer, Sprout, Strategic Science Technologies, and Vella; and stock options from Alloy. N.S., C.M., and S.S. are employees of Bayer AG, Germany. C.C. and C.J. are employees of Bayer Consumer Care, Switzerland. M.S. and M.H. are employees of Adelphi Real World, UK. L.H. is an employee of Bayer US. V.B. was an employee of Bayer, UK at the time of the study. R.E.N. has past financial relationships (lecturer, member of advisory boards, and/or consultant) with Boehringer Ingelheim, Eli Lilly, Endoceutics, MSD, Palatin Technologies, Pfizer, Procter & Gamble, Teva Women's Health, and Zambon; has ongoing relationships with Abbott, Astellas, Bayer HealthCare, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck & Co, Novo Nordisk, Organon, Shionogi, Theramex, and Viatris; and serves as President-Elect of the International Menopause Society (IMS)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess clinical characteristics of postmenopausal women with moderate/severe vulvovaginal atrophy, as well as its impact on sexual function, well-being, and quality of life, and to provide an overview of most used treatments., Study Design: Ongoing longitudinal, observational study conducted in 17 Italian gynecology centers, involving women already treated or initiating a local vaginal estrogen therapy or ospemifene. We report baseline data for women with and without a history of breast cancer. Participants filled in self-reported questionnaires at study entry., Main Outcome Measures: Severity of vulvovaginal atrophy; ongoing treatments; patient-reported outcomes, including severity of symptoms, Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and SF-12® Health Survey., Results: Overall, 334 women (20.4 % with a history of breast cancer) started or continued local therapy (61.1 %) or ospemifene (38.8 %) at study entry. Vulvovaginal atrophy was severe in 28.6 %, and was responsible for severe symptoms, particularly vulvar dryness with burning or irritation and pain during sexual intercourse. Both sexual dysfunction (FSFI≤26) (81.5 %) and sexual distress (FSDS-R ≥ 11) (74.4 %) were common. A reduction in the SF-12 mental component score was documented. Women with breast cancer more often had severe vulvovaginal atrophy (41.2 %), had more severe symptoms, and the impact of vaginal symptoms on emotional well-being, sexual functioning and self-concept/body image was greater. The majority of them (83.8 %) received ospemifene as a treatment., Conclusions: Moderate/severe vulvovaginal atrophy is a common, often neglected condition with an impact on QoL and sexuality, particularly in women with a history of breast cancer. It is important to alleviate the burden associated with the disease., Competing Interests: Declaration of competing interest REN had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Palatin Technologies, Pfizer Inc., Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck Sharpe & Dohme, Novo Nordisk, Organon & Co, Shionogi Limited, Theramex, and Viatris. TDP is an employee of SHIONOGI S.r.l. AN has financial relationships (support to research, lecturer, consultant) with AlfaSigma, Astra Zeneca, Eli Lilly, Novo Nordisk, Sanofi, Shionogi, Theras, SOBI. PV has financial relationship (presentations, speakers bureaus, manuscript writing or educational events) with PharmExtracta, Bromatech. Shionogi, Amgen. MCM had financial relationship (lecturer, consultant) with Bayer HealthCare AG, Exeltis, Gedeon Richter, Organon & Co, Sandoz, Shionogi Limited and Theramex. The other authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The huge impact of climate change on humankind is multidimensional, and includes direct and indirect challenges to the physical, psychological and socio-cultural wellbeing. Women may be more vulnerable to climate-sensitive diseases, but little attention has been paid to specific needs and challenges associated with the menopause transition. The increase in average and extreme temperatures may modulate the manifestation of vasomotor symptoms; in particular, environmental temperature and seasonality may affect hot flushes and night sweats. However, more research is needed to define the impact of climate-related factors among the determinants influencing the individual experience of menopause. In addition, increased exposure to environmental pollution and toxins may also have a role in the modulation of ovarian aging mechanisms, possibly influencing timing of menopause. Finally, both air pollution and menopause transition are associated with unfavorable modifications of cardio-metabolic, bone and cognitive health, and account should be taken of these in the evaluation of the individual woman's health vulnerabilities. Overall, the evidence reported in this narrative review supports the need for specific strategies aimed at reducing the burden of climate and environmental change on menopausal women. Healthcare providers should promote behavioral measures that reduce anthropogenic climate change and at the same time have a beneficial role on several domains of physical and psychological wellbeing. From this perspective, menopause represents a golden moment to implement virtuous behaviors that will benefit at the same time women's longevity and the planet., Competing Interests: Declaration of competing interest Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Gedeon Richter, HRA Pharma, Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Astellas, Bayer HealthCare AG, Exeltis, Fidia, Merck Sharpe & Dohme, Novo Nordisk, Palatin Technologies, Pfizer Inc., Shionogi Limited, Theramex, and Viatris. None of these are relevant to the present work. All the other authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17β-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens., Study Design: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records., Main Outcome Measures: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA., Results: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92)., Conclusions: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA., Competing Interests: Declaration of competing interest N. Panay has lectured and acted in an advisory capacity for a number of pharma companies, including Theramex. R.E. Nappi has lectured and acted in an advisory/consultant capacity for a number of pharma companies, including Theramex. P. Stute has been a consultant with honorarium for Theramex. S. Palacios has been a consultant with honorarium for Theramex and has lectured and acted in and advisory/consultant capacity for other pharma companies. T. Paszkowski has been a consultant with honorarium for Theramex and received honoraria as consultant/member of advisory boards/lecturer from a number of pharma companies, including Theramex. R. Kagan has been an Advisor/Consultant with honorarium and has lectured for a number of pharma companies, including TherapeuticsMD. D. F. Archer has been a consultant with honorarium for a number of pharma companies, including TherapeuticsMD. J. Heroux is an employee and the owner of Heroux Consulting, which received research funding for the conduct of the current study. M. Boolell is an employee of and stockholder in Theramex., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine, in a European cohort, the prevalence and health-related quality-of-life (QOL) burden of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women, and among subgroups of women not taking hormone therapy (HT)., Study Design: Screening surveys were sent to a random sample of women aged 40-65 years; those meeting the inclusion criteria completed the full questionnaire. Women with successfully treated VMS or breast cancer or who were receiving HT for medical conditions were excluded., Main Outcome Measures: Frequency and duration of VMS, perceptions of menopause, seeking advice from a healthcare professional, treatment for VMS symptoms, perceptions of HT use, out-of-pocket costs, and other approaches to coping with menopause. The Menopause-Specific QOL (MENQOL) questionnaire and Work Productivity and Activity Impairment (WPAI) questionnaire were included., Results: Of 11,452 women who completed the screening survey, 5178 were postmenopausal and 2035 completed the full questionnaire. Prevalence of moderate-to-severe VMS ranged from 31 % in France to 52 % in Italy. The majority were in the HT-caution or HT-averse group, despite being eligible for HT. Most common menopausal symptoms reported in the MENQOL were "feeling tired or worn out," with aching in muscles and joints reported as the most common symptom in Spain. Weight gain was the most bothersome symptom in all countries, except for Spain, where low backache was more bothersome. Hot flashes and night sweats had a greater impact on daily than on working activities, as measured by the WPAI., Conclusions: A high proportion of European women reported experiencing moderate-to-severe VMS, with associated symptoms influencing QOL., Competing Interests: Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards, and/or consultant) with Boehringer Ingelheim, Eli Lilly, Endoceutics, Gedeon Richter, HRA Pharma, Merck Sharpe & Dohme, Palatin, Procter & Gamble, Teva Women's Health, and Zambon. At present, she has ongoing relationships with Abbott, Astellas, Bayer, Exeltis, Fidia, Novo Nordisk, Organon, Pfizer, Shionogi, and Theramex. She serves as General Secretary Elected of the International Menopause Society. Emad Siddiqui, Lora Todorova, and Neil M. Schultz are employees of Astellas. Carol Rea and Eric Gemmen declare that they have no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Female sexual function relies on a complex interplay of physical, psychosocial, and neurobiological factors. Over the last decades, increasing attention has been paid to the influence of personality traits on general health and many aspects of quality of life, including sexuality., Objective: To assess whether dimensions of the personality are related to the domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) in symptomatic postmenopausal women. Mood was also investigated to explore its association with female sexual dysfunction (FSD)., Methods: Validated questionnaires to assess sexual function [the Female Sexual Functioning Index (FSFI)], mood [the State-Anxiety Inventory (STAI), and Zung Self Rating Depression Scale (SDS)], and personality traits [the Tridimensional Personality Questionnaire (TPQ)] were filled in by 130 early postmenopausal women experiencing hot flushes (≥30/week)., Results: 61.5 % (n = 80) of the women had an FSFI total score lower than 26.55, the standard cut-off for FSD. A clinical state of anxiety was present in 53.8 % (n = 70), whereas only 12.3 % (n = 16) showed clinically relevant depressive symptoms. According to the FSFI cut-off score, women with sexual disorders had statistically significantly higher levels of anxiety, depression (p < 0.001 for both), and harm avoidance (HA) (p = 0.004) than women without such disorders. Significantly higher levels of anxiety were found in women in the lower quartile (LQ) of the distribution of the total FSFI score than in women in both the interquartile range (IQR) and in the upper quartile (UQ) (p < 0.05). Moreover, women in the UQ had a lower grade of depression and HA than others (p < 0.05). The Sobel test showed that the personality trait HA significantly mediated the relationship between anxiety and FSFI total score (Z = -2.19, p < 0.05) and between depression and FSFI total score (Z = -2.35, p < 0.05)., Conclusions: The present data suggest the personality trait HA is relevant to sexual function and mediates the impact of mood on FSD in symptomatic menopausal women. In clinical practice, the use of validated psychometric tools for mood screening is useful to establish appropriate diagnosis and treatment of sexual disorders in menopausal women. Moreover, the assessment of personality traits could provide additional information that directs clinicians towards an increasingly tailored and multidimensional treatment of FSD., Competing Interests: Declaration of competing interest Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Palatin Technologies, Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Astellas, Bayer HealthCare AG, Exceltis, Fidia, Gedeon Richter, HRA Pharma, Merck Sharpe & Dohme, Novo Nordisk, Pfizer Inc., Shionogi Limited and Theramex. None of these are relevant to the present work. All the other authors have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The severity and mortality rate of COVID-19 differ between the sexes. Several biopsychosocial determinants may account for the better outcomes in women. The notion that sex steroid hormones account for the gender disparity is reasonable but not proven; the same is true of the role of menopause as a risk factor. A retrospective analysis of patients (=1764) hospitalized in Italy showed a higher mortality (HR 1.58, 95%CI 1.30-1.91, adjusted for age and multi-comorbidities) in males only after the age of 65 (the rate is twice as high in the 65-79-year age group and 1.5-fold higher in those aged over 80). The higher mortality of men is mostly evident among those aged over 65 years, long after the average age of menopause., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18β-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks., Study Design: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days., Main Outcome Measure: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function., Results: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .0001), and in reducing each VVA symptom (vaginal dryness, vaginal itching, burning sensation) at weeks 2 and 4, and the end of the study (P < .0001). The analysis of FSFI scores showed, after the end of treatment, an improvement of sexual function in the active-treatment group, with a statistically significant increase (P < 0.001) in all domains scores and total score (P < 0.001)., Conclusions: The present single-center randomized clinical trial demonstrated the efficacy, tolerability and safety of 12-week treatment with a new vaginal gel in postmenopausal women with symptoms associated with VVA. Based on this trial, the gel seems to be a valid choice as a single, local agent for relieving VVA symptoms and improving sexual function, and to have good compliance. This trial is registered prospectively with the Clinical Trials Registry - India, number CTRI/2019/05/01911., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: we aimed to explore the use of an estro-androgenic symptom questionnaire in women (EASQ-W), including items typically associated with menopausal hypoestrogenism and some others possibly related to androgen insufficiency that may be relevant to further characterize women reporting VVA/GSM at midlife., Methods: web-based survey involving a representative sample of 1505 Italian women (age range: 40-65 years). The responders completed a structured, online questionnaire, reporting symptoms (yes/no option) and rating them (from 1 to 10), if present during the past 4 weeks. A factor analysis methodology (principal component analysis and K-MEANS clustering algorithm) was used to segment women. Statistically significant differences between groups were determined at the 95 % level of confidence., Results: more than half of our study sample were aged 50-65 years (n = 901; 59.9 %) and 55 % were postmenopausal women (PMW). We obtained 8 principal domains of the EASQ-W with PMW reporting significantly more severe symptoms in the majority of domains related to well-being at mid-life. The K-MEANS clustering algorithm identified 4 clusters of women characterized by different symptoms: vasomotor (VMS; n = 341), sexual (SEX; n = 301), poorly symptomatic (LOWSYMPT; n = 766), sexual and anatomic, mainly at genital level (SEX + ANAT; n = 97), independently from the menopausal status. The cluster SEX + ANAT was the one reporting overall more symptoms in each of the other principal domains. Some symptoms (impression of being diminished in height, deterioration in work performance, more memory lapses/confusion than before, more wrinkles/signs of aging in the mirror, put on more tummy than usual) and the entire urological (UROL) cluster were significantly more reported by women in the cluster SEX + ANAT. Even when only severe symptoms were analysed, women in the SEX + ANAT cluster were the ones more symptomatic. The SEX only cluster identified younger women, with significantly less day and night hot flushes and sweats and less vaginal dryness and low lubrication associated with sexual pain as compared to SEX + ANAT., Conclusion: our results provide insight into the constellation of symptoms associated with VVA/GSM by identifying women with distinct clusters of complaints that may require a tailored diagnostic and therapeutic approach across age and menopause., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the association between treatments for vulvovaginal atrophy (VVA) and symptom frequency and severity, quality of life (QoL) and sexual functioning in postmenopausal women., Study Design: Cross-sectional survey conducted in postmenopausal women aged 45-75 years. Data on demographic and clinical variables, as well as vaginal, vulvar and urinary symptoms were collected. The EuroQoL questionnaire (EQ5D3L), the Day-to-Day Impact of Vaginal Aging (DIVA), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale - revised (FSDS-R) were filled out., Main Outcome Measures: Association between treatments for VVA and symptom frequency., Results: Women on VVA treatment presented with more severe symptoms. The sexual function score was higher in the treated women (FSFI: 15.6 vs 16.7; p = 0.010), as was the score for sexual distress (FSDS-R: 9.2 vs 12.3, p < 0.0005). The systemic hormone group presented with fewer VVA symptoms, lower vaginal impact (DIVA), and better sexual function (FSFI and FSDS-R) and vaginal health. The rates of sexual distress and vulvar atrophy were higher in the non-hormonal treatment group. No significant differences were found according to treatment duration., Conclusions: Postmenopausal women with VVA receiving treatment complained of more severe symptoms than those untreated. Women on systemic treatment had fewer and milder VVA symptoms and presented with better vaginal and vulvar health than women on other treatments. Many women request effective local treatment too late, when VVA symptoms are already severe. Our data suggest that VVA treatments should ideally be initiated when symptoms commence and cause distress, rather than later, when symptoms may have become more severe and even a cause of intolerable distress for the woman., (Copyright © 2019. Published by Elsevier B.V.)

Female sexual dysfunction (FSD) and quality of life (QOL) are both multidimensional and have a bidirectional relationship across the reproductive life span and beyond. Methodological difficulties exist in estimating the real prevalence of FSD because it is hard to determine the level of distress associated with sexual symptoms in a large-scale survey. Approximately 40-50% of all women report at least one sexual symptom, and some conditions associated with hormonal changes at menopause, such as vulvovaginal atrophy (VVA) and hypoactive sexual desire disorder (HSDD), have a significant impact on sexual function and QOL. Sexual distress peaks at midlife, declines with age and is strongly partner-related. Many postmenopausal women are still sexually active, especially if they are in a stable partnership. Even though sexual functioning is impaired, a variety of psychosocial factors may maintain sexual satisfaction. That being so, health care providers (HCPs) should proactively address sexual symptoms at midlife and in older women, from a balanced perspective. Adequate counselling should be offered. Women with distressing symptoms may benefit from tailored hormonal and non-hormonal therapies, whereas women without distress related to their sexual experiences should not receive any specific treatment., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To achieve a better comprehension of the variability of perceptions, experiences and needs in terms of sexual and vaginal health in postmenopausal women (PMW) from four different European countries., Methods: An internet-based survey was conducted in Italy, Germany, Spain and the United Kingdom with a total surveyed population of 3768 PMW aged between 45 and 75 years., Results: The UK sample was significantly older, with almost a quarter of participants over 65 years of age, and had the highest proportion of women experiencing recent vulvar and vaginal atrophy (52.8%). The majority of Italian and Spanish participants were receiving VVA treatment, whereas in the UK only 28% of PMW were on medication. The most common menopausal symptom was vaginal/vulvar dryness, with almost 80% of participants reporting it in all the countries except the UK (48%). On the other hand, vaginal/vulvar irritation was more frequently reported in the UK (41%). The percentage of participants with a partner was lower in the UK (71%), as was the monthly rate of sexual activity (49%). In the UK, the proportion of participants who had seen a healthcare professional for gynaecological reasons in the last year was lower than in other countries (27% vs. ≥50%), as was the proportion who has discussed their VVA symptoms with them (45% vs. ∼67%). In this sense, UK PMW waited for a longer before asking for help (especially for pain with intercourse and dryness). The main issues relating to VVA treatment difficulties expressed by participants were administration route in the UK, efficacy in Germany, and side-effects in Italy., Conclusions: Although all European women shared the same expectation of improving the quality of their sex lives, the opportunity for that varied among different countries in relation to the healthcare system and to the effective communication achieved with healthcare professionals when managing VVA., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objectives: To achieve a deeper understanding of the attitudes and perceptions of Italian post-menopausal women (PMW) regarding vulvo-vaginal atrophy (VVA)., Study Design: As part of the EU REVIVE study, an online survey was conducted in four European countries; the Italian arm comprised 1000 participants from representative regions of Italy., Main Outcome Measures: The perceptions, experiences and needs of Italian PMW in relation to sexual and vaginal health., Results: The most frequent VVA symptom was vaginal dryness (78%). Usually, the severity of symptoms was similar to or worse than when they first appeared. This was particularly true for dyspareunia, the most bothersome symptom (76%). VVA symptoms had a significant impact on Italian participants' ability to achieve pleasurable relations (74%) and spontaneity (70%). Although 75% of participants were still sexually active, their sex drive had been reduced by a third because of VVA. Women expected that doctors would start a discussion of menopausal symptoms and sexual health, but this was rarely the case (11%). Most women had been treated with a vaginal over-the-counter (OTC) product. Women who had discussed their condition with a physician were more likely (68%) to be under treatment for VVA than those who had not (36%). Low compliance was associated with symptom improvement (23%), not having annoying symptoms (22%), and the impossibility if restoring the vagina to normal (14%). Common reasons for treatment dissatisfaction were related to route of administration or discomfort. Lack of efficacy and fear of a hormone effect were perceived as the main limitations for OTC and local estrogen products, respectively., Conclusions: Despite the commonness of VVA and its significant impact on quality of life, the condition remains underdiagnosed in Italy. Discussion of symptoms with doctors influences the diagnosis, and patients' satisfaction with available treatments is not high., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The term genitourinary syndrome of menopause (GSM) emerged following a consensus conference held in May 2013. GSM is a more descriptive term than vulvovaginal atrophy (VVA) and does not imply pathology. However there are concerns that GSM is all encompassing and includes not only symptoms resulting from estrogen deficiency, but also those arising from the effects of ageing and other processes on the bladder and pelvic floor. Focusing on symptoms related to estrogen deficiency, the update provides a practical guide for health and allied health professionals on the impact of GSM on women and their partners, assessment, management and areas for future research. As GSM is a chronic condition, long term therapy is required. Hormonal, nonhormonal, laser and alternative and complementary therapies are described., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Vulvovaginal atrophy (VVA), also known as genitourinary syndrome of menopause, exerts a negative impact on the sexuality, health and quality of life of post-menopausal women. A better understanding of post-menopausal women's profiles as defined by their attitude and behaviours in relation to their VVA symptoms may improve public health policies and will allow appropriate targeting of public health campaigns. These improvements may help women of middle and advanced age recover and maintain their quality of life. In this study, we analysed the attitudes of post-menopausal women, aged 45-74 years, with VVA symptoms from five European countries, with the aim of identifying profile markers to improve healthcare strategies., Methods: Two consecutive cross-sectional studies were conducted in five European countries (the UK, France, Spain, Germany and Italy). An initial exploratory study (n=69) was based on interviews and then an analytical study (n=749) was based on online surveys to validate women's profiles by means of a multi-level approach., Results: We identified eight profiles: self-treater, pragmatic, vivacious, reserved, silent sufferer, expressive, stoic and sad. The percentage distribution varied among the countries. The 'pragmatic', 'vivacious' and 'expressive' women were the most proactive, talkative and open with their healthcare professional, whereas women with the 'reserved' and 'stoic' profiles showed less interest in searching for information about their VVA symptoms, either from their healthcare professional or from other sources., Conclusions: The attitudes and behaviours of post-menopausal women in relation to their VVA allow for the clear definition of a series of profiles with varying representation across countries. This study reveals the importance of identifying post-menopausal women's profiles to develop interventions to help them overcome barriers to the diagnosis, management and treatment of VVA., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: CLOSER investigated how postmenopausal vaginal atrophy ('vaginal discomfort') affects relationships between women and their partners., Study Design: CLOSER involved postmenopausal women (55-65 years) with vaginal discomfort, and male partners of women with the condition., Main Outcome Measures: Structured questionnaire collecting information on impact of vaginal discomfort and local oestrogen treatment on intimacy and relationships, and symptoms and impact of menopause., Results: 1600 women and 1600 men from Northern Europe and 1000 women and 1000 men from Southern Europe were included. Worry that vaginal discomfort would never go away was expressed by 28% and 38% of women in Northern and Southern Europe, respectively (p<0.05), while 21% and 27% worried that vaginal discomfort would ruin their future sex life (p<0.05). Half of women who avoided intimacy worried about painful sex. Among men, 86% wanted their partner to talk about symptoms; two-thirds felt comfortable with this. In Northern and Southern Europe, 15% and 11% of men, respectively, feared that discussing vaginal discomfort would ruin intimacy, while 29% and 19% believed that vaginal discomfort was a big problem in their sex life. Men with partners who avoided intimacy recognised that worry about painful sex was the main reason. Vaginal discomfort impaired self-esteem and emotional wellbeing among women, while local oestrogen treatment improved relationships, particularly in Southern Europe., Conclusions: Vaginal discomfort impairs quality of life in postmenopausal women and their partners. Southern European women were generally more worried about long-term effects on their relationship, and were more likely to report benefits after treatment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To consider issues relating to vaginal atrophy via an international survey., Methods: Using a structured questionnaire, interviews were performed on 4246 women aged 55-65 years living in Sweden, Finland, the United Kingdom, the United States and Canada., Results: Overall, 98% of survey respondents were postmenopausal. Thirty-nine percent of the postmenopausal women had experienced vaginal atrophy, with the prevalence varying between countries, from 34% in Canada to 43% in Finland and the United States. Attitudes towards symptoms also varied between countries. Symptoms were described as moderate or severe by less than half of women from Finland and Sweden, compared with nearly two-thirds of women from the United States. However, vaginal atrophy was deemed to impact on quality of life by a higher proportion of women in Finland and Sweden (≥60%) than in the United Kingdom, the United States and Canada (≤50%). Overall, 77% of respondents believed women were uncomfortable discussing vaginal atrophy and 42% did not know that local treatment was available. The proportions of women unaware of the availability of local treatment were higher in the United States, the United Kingdom and Canada (51%, 50% and 48%, respectively), and very low in Finland (10%). Whilst 63% of women who had experienced vaginal atrophy had never been prescribed treatment for the condition, 67% of those who had been treated reported positive effects., Conclusion: The survey results illustrate differing needs of menopausal women in different countries. Country-specific approaches may be required to improve the uptake of treatment for vaginal atrophy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of the present observational, cross-sectional study was to examine the effects of hormonal and psycho-relational variables on sexual function during menopausal transition and at early postmenopause in women with hot flushes., Study Design: The sample comprised 138 women referred to a clinic for the treatment of hot flushes. They were categorised according to their stage of menopausal transition using the STRAW criteria: early menopausal transition (EMT) if their menstrual cycle was 7 or more days different from normal; late perimenopause (LMT) if they had experienced 60 days or more of amenorrhoea; and early postmenopause (EPM) if their amenorrhoea had lasted for at least 12 months but less than 4 years., Main Outcome Measures: Sexual function was measured by using the Female Sexual Function Index (FSFI), while anxiety (state and trait), depression, eating disorder and marital adjustment were evaluated by validated self-report questionnaires. Levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and estradiol (E2) were also measured., Results: Overall sexual function varied significantly with stage of menopause, with total FSFI score less in EPM than in EMT (p=.009). A similar pattern was evident on FSFI sub-scales for sexual desire (p=.02), arousal (p=.01) orgasm (p=.01) and also pain (p=.02), but not for lubrication and satisfaction. Ratings for anxiety, depression and eating disorder did not differ across the menopausal sub-groups, and neither did ratings of marital adjustment. Both FT (p=.01) and DHEAS (p=.03) levels were slightly reduced at EPM in comparison with EMT, as were E2 levels (p=.001 EMT versus LMT; p=.0001 LMT versus EPM). In multiple regression analyses, plasma FT level was the only factor to predict FSFI full score (beta=.48; p=0.004) in women at EMT, while in women at LMT the depression score was the only factor to do so (beta=-.62; p=0.0001). The best model predicting FSFI full score at EPM included levels of DHEAS and E2 levels and state anxiety score., Conclusions: Hormonal and some psychological variables are relevant to sexual function in symptomatic women during menopausal transition and at early menopause but their role differs with the specific stage of reproductive ageing., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: This article aims to summarise the available knowledge on the prevalence of sexual symptoms at the menopause and their impact on quality of life in elderly women. Sexual changes are analysed in the context of the menopause transition and beyond., Methods: The medical literature was searched (1990-2008) with regard to menopause and sexuality using several related terms., Results: The prevalence of sexual symptoms at the menopause differs across studies depending on several factors such as sample size, design, hormonal status and country. The most common sexual complaints are reduced sexual desire, vaginal dryness and dyspareunia, poor arousal and orgasm and impaired sexual satisfaction. Age and declining oestradiol levels have significant detrimental effects on sexual functioning, desire and responsiveness (arousal, sexual pleasure and orgasm) across the normal menopause transition, while reduced androgens levels played a role in hypoactive sexual desire disorder (HSDD), a symptom frequently diagnosed in surgically menopausal women., Conclusions: Women attending menopause clinics are vulnerable to female sexual dysfunction (FSD) because of a complex interplay of individual factors variably affecting well-being. Surgically menopausal women may be more distressed by sexual symptoms. Giving women the opportunity to talk about sexual problems is a fundamental part of health care and may improve their quality of life.

The decline in sex hormone levels that accompanies the menopause has substantial effects on the tissues of the urogenital system, leading to atrophic changes. These changes can have negative effects on sexual and urinary function, leading to dyspareunia and incontinence. Treatment of urogenital atrophy with systemic or local oestrogens can improve the adverse effects of loss of oestrogen on both sexual and urinary functions. In some cases, treatment with oestrogen alone may not be sufficient to address sexual problems in menopausal women and androgen addition is required. Because of the complexity of sexual problems in menopausal women, assessment and therapy should address both the physical and other factors that play a role in the condition.

Background: The effect of persistence with transdermal and oral administrations of hormone replacement therapy (HRT) on the risk of hospitalisation for cardiovascular disease, and the role of income as potential confounder, were explored in a large population-based cohort study., Methods: Seventy-eight thousand eight hundred and seventy-five women resident in the Italian Lombardy Region aged 45-65 years who received at least one HRT prescription during 1998-2000 were followed until December 2003. The 828 cohort members who experienced at least one hospitalisation for a circulatory system disease were identified from the Regional hospital discharge database. The Regional prescription drug database was used to assess cumulative persistence with hormone treatment during follow-up. Data on individual taxable income was also obtained for women resident in the city of Milan. A proportional hazards model was fitted to estimate the association between cumulative time-dependent persistence with HRT and cardiovascular risk., Results: Compared with women who took HRT for less than 6 months, those exposed for more than 3 years to HRT as a whole, and to transdermal and oral HRT, respectively, showed hazard ratios of 0.65 (95% confidence interval: 0.45, 0.92), 0.53 (0.34, 0.82), and 1.15 (0.47, 2.79). CVD reducing potential of HRT disappeared when estimates were adjusted for income being hazard ratio associated with long-term use 0.94 (0.52, 1.71)., Conclusions: Evidence that CVD risk associated with long-term hormone treatment varies according to the route of HRT administration, and that economic position confounds the effect of HRT on the risk of cardiovascular hospitalisation, is provided by the current study.

Objective: The aim of the present pilot, randomized, study was to assess hemodynamic status of clitoral erectile tissues in postmenopausal women reporting female sexual dysfunction (FSD), namely libido and arousal disorders, under hormone therapy (HT). Vaginal health and sexual function were also investigated., Study Design: Fifty patients presenting for clinical evaluation of menopausal status and suffering from FSD were randomly assigned to receive tibolone (2.5 mg) or 1 mg 17beta-estradiol .5 mg NETA (EPT) for 6 months. The observational period lasted 7 months during which women underwent to duplex Doppler ultrasonography to obtain clitoral hemodynamic data, were evaluated by using the vaginal health score index (VHIS) and filled in the two-factor Italian McCoy female sexuality questionnaire (MFSQ)., Results: Tibolone significantly increased clitoral peak systolic and end diastolic velocity (p<.001 for both), while no significant difference was evident in clitoral circulation of women under EPT at the end of the study. Both tibolone and EPT significantly increased VHIS (p<.001), an effect already evident following 3 months of HT. The atrophic state was significantly improved at 6 months (p<.001) with no significant differences between the two HT regimens. After 3 months, both tibolone and EPT significantly increased the sexuality score (p<.001, for both), but such an effect was significantly more pronounced in FSD women treated with tibolone in comparison with those assuming EPT (p<.002). Between the 3rd and the 6th month, tibolone caused a further significant improvement of sexuality score (p<.001), while women under EPT did not show any significant further change displaying a lower score (p<.001) at the end of the study in comparison with women assuming tibolone., Conclusions: Clitoral circulation in postmenopausal women reporting FSD is significantly increased under tibolone in comparison with EPT with a better improvement of sexual function, as measured by MFSQ, following 6 months of treatment.