Menopause: The Journal of The North American Menopause Society最新文献

{"title":"Impact of hormone therapy on mood in a real-world clinical setting: a retrospective observational study.","authors":"Samantha Fairweather, Laurie Jeffers, Dana R Gossett, Emily Friedman, Alberta Twi-Yeboah, Samantha Dunham","doi":"10.1097/GME.0000000000002873","DOIUrl":"https://doi.org/10.1097/GME.0000000000002873","url":null,"abstract":"<p><strong>Objective: </strong>Mood disturbances-including depressed mood, irritability, anxiety, and mental exhaustion-are common during the menopause transition, affecting up to 68% of women. While menopausal hormone therapy (HT) is FDA-approved for vasomotor and genitourinary symptoms, its role in managing mood symptoms remains less well understood. This retrospective, comparative study evaluated the impact of systemic HT on mood in a cohort of HT-naive individuals.</p><p><strong>Methods: </strong>We included 260 patients presenting to an urban, academic menopause center between 2023 and 2025 who completed the Menopause Rating Scale (MRS) before and after initiating systemic HT for FDA-approved indications. MRS psychological subdomain scores covering depressive mood, irritability, anxiety, and mental exhaustion were analyzed. Most patients (96.5%) received transdermal estradiol, had an average age of 52.1 years, and a mean follow-up of 4.5 months. Notably, 51% had a history of anxiety or depression, and 24% were on antidepressant therapy at baseline.</p><p><strong>Results: </strong>Results showed a significant reduction in MRS psychological subdomain scores from baseline to follow-up (P<0.001). The proportion of patients with severe mood symptoms (score ≥7) decreased from 62.3% to 24.6%. Improvement was greatest in those with severe baseline symptoms (mean change: -3.85, SE: 0.223). Treatment response did not differ by psychiatric history, age, menopausal stage, or antidepressant use.</p><p><strong>Conclusions: </strong>These findings suggest systemic HT may improve mood symptoms in midlife, especially among those with elevated baseline severity, independent of prior mental health diagnosis, antidepressant use, or menopause stage. These findings support further investigation of HT's impact on mood in midlife women.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of coronary artery calcium in the association between hormone therapy status and incident death and cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.","authors":"Rachelle Bishay, Keishi Ichikawa, April Kinninger, Srikanth Krishnan, Nathan D Wong, Erin D Michos, Ahmed Ghanem, Marziyeh Bagheri, Hossein Hamidi, Matthew J Budoff","doi":"10.1097/GME.0000000000002891","DOIUrl":"https://doi.org/10.1097/GME.0000000000002891","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether coronary artery calcium (CAC) modifies the association between hormone therapy (HT) use and cardiovascular disease (CVD) events.</p><p><strong>Methods: </strong>A total of 3,235 female participants free of clinical CVD at baseline were included from the Multi-Ethnic Study of Atherosclerosis and monitored for incident CVD. HT status was self-reported and categorized as never, former, and current users. Cox proportional hazards regression models were fit to examine the relationships between HT and CVD outcomes, with and without CAC (as categories), including standard risk factors as covariates.</p><p><strong>Results: </strong>Participants were 63.4 ± 9.8 years of age, and 90% were postmenopausal. There were 1,024 (32%) current, 1,618 (50%) never, and 593 (18%) former HT users. Current HT users were significantly younger, more likely to be White, had lower prevalence of diabetes mellitus, and higher education and income levels. During the 14.4-year follow-up period, 734 deaths (14.8 per 1000 person-years) and 454 CVD events (10.1 per 1000 person-years) were identified. In multivariable Cox regression analysis including CAC, current HT use versus never use was associated with lower risk for all-cause death (hazard ratio [HR]: 0.70, 95% CI: 0.58-0.86) and in current versus former users (HR: 0.77, 95% CI: 0.61-0.98). Former users did not differ significantly from never users in risk of death or cardiovascular outcomes. Addition of CAC to adjusted models did not meaningfully modify the association between HT status and all-cause death (HR: without CAC: 0.69 [0.57-0.85]; HR with CAC: 0.70 [0.58-0.86]).</p><p><strong>Conclusions: </strong>Women who received HT have a significantly lower risk of all-cause death compared with never and former users, with CVD and coronary heart disease outcomes trending lower but not reaching statistical significance after adjustment. CAC did not modify the observed association between HT and mortality.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.","authors":"Jack W Staples, Samantha L White, Adam Giacalone, Nikita Pozdeyev, Mary D Sammel, Barbara E Stranger, Celina I Valencia, Nanette Santoro, Audrey E Hendricks","doi":"10.1097/GME.0000000000002884","DOIUrl":"https://doi.org/10.1097/GME.0000000000002884","url":null,"abstract":"<p><strong>Objectives: </strong>Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses.</p><p><strong>Methods: </strong>We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics.</p><p><strong>Results: </strong>Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N≈1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry).</p><p><strong>Conclusions: </strong>These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimated impact of fezolinetant versus placebo on work productivity and indirect costs among women experiencing vasomotor symptoms associated with menopause.","authors":"Antonia Morga, Ting-An Tai, Ritika Kapoor, Wei Song, Qi Hua, Yechu Hua, Hongbo Yang, Mayank Ajmera","doi":"10.1097/GME.0000000000002755","DOIUrl":"10.1097/GME.0000000000002755","url":null,"abstract":"<p><strong>Objectives: </strong>This study evaluated the impact of fezolinetant versus placebo on work productivity and indirect costs among women with moderate to severe vasomotor symptoms (VMS) associated with menopause in seven countries.</p><p><strong>Methods: </strong>This post hoc analysis used Work Productivity and Activity Impairment (WPAI) questionnaire data from the SKYLIGHT 1 (NCT04003155), SKYLIGHT 2 (NCT04003142), and DAYLIGHT (NCT05033886) trials to compare absenteeism, presenteeism, and productivity loss among fezolinetant-treated versus placebo-treated women with moderate to severe VMS (population 1) and among these women for whom hormone therapy (HT) was unsuitable (population 2). Missed work time was calculated as the product of patient-reported work productivity loss and country-specific work hours and employment rates extracted from publicly available, country-specific sources. Annualized indirect costs were estimated based on missed work time and country-specific estimated salaries.</p><p><strong>Results: </strong>Over 1 year, fezolinetant improved work productivity versus placebo. In population 1, increases ranged from 2.8 (Brazil) to 4.2 (United States) weekly work hours per woman with fezolinetant versus placebo. Fezolinetant resulted in estimated annualized cost savings per woman versus placebo in population 1 of 7,791 USD (United States), 7,295 CAD (Canada), 3,878 GBP (United Kingdom), 8,953 AUD (Australia), 6,193 EUR (Germany), 3,901 EUR (France), and 2,754 BRL (Brazil). Overall work productivity loss improved with fezolinetant versus placebo (population 1: -12.4% [ P <0.0001]; population 2: -10.2% [ P <0.0001]).</p><p><strong>Conclusions: </strong>Fezolinetant demonstrated improvements in work productivity and reduced estimated indirect costs versus placebo for women with moderate to severe VMS, including HT-unsuitable women who often face limited treatment options, maintained through 52 weeks.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":"975-987"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A perspective on the revised American College of Obstetricians and Gynecologists' guidance for transvaginal ultrasound in the evaluation of postmenopausal bleeding.","authors":"Steven R Goldstein","doi":"10.1097/GME.0000000000002902","DOIUrl":"https://doi.org/10.1097/GME.0000000000002902","url":null,"abstract":"<p><p>The American College of Obstetricians and Gynecologists (ACOG) recently revised its guidance regarding the evaluation of postmenopausal bleeding (PMB), recommending combined transvaginal ultrasonography (TV U/S) and endometrial (EM) sampling for most patients undergoing initial assessment. This perspective examines the evidence underlying these recommendations and considers their potential implications for clinical practice. Prior ACOG guidance recognized that, when the endometrium is fully visualized and measures ≤4 mm, TV U/S provides a highly effective means of excluding endometrial cancer (EC) in most women with PMB if the TV U/S is adequate and there is no persistent bleeding. Their revised recommendations place greater emphasis on EM sampling, including in several patient populations previously considered appropriate candidates for ultrasound-based evaluation. This perspective reviews the evidence this new guidance relied upon, as well as limitations of blind EM sampling, including published false-negative rates even in cases of known carcinoma, technical challenges associated with tissue acquisition, and potential procedural complications. Particular attention is given to women receiving menopausal hormone therapy, as well as nulliparous women in whom EM sampling may be technically difficult. My perspective is that former guideline-based approaches remain generally appropriate. The concern about the increasing mortality of EC in the United States is appropriate, as is the concern about racial disparities in the incidence and mortality of EC. However, the new ACOG revision will result in inappropriate, invasive EM sampling in a large number of women. The potential harms, as well as difficulties in obtaining tissue, will be substantial. Any real attempt to reduce the mortality of EC will require a better understanding of patient-specific risk factors, as well as information about less common non-EM type II cancers, especially in Black women, and better patient and practitioner education relative to PMB.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social support and cognitive function in postmenopausal women.","authors":"Felice Lin, Irene Chen, Judy Pa, Roksana Karim, Howard N Hodis, Biing-Jiun Shen, Uta Maeda, S Duke Han, Victor W Henderson, Jan A St John, Wendy J Mack","doi":"10.1097/GME.0000000000002877","DOIUrl":"https://doi.org/10.1097/GME.0000000000002877","url":null,"abstract":"<p><strong>Objective: </strong>An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women.</p><p><strong>Methods: </strong>The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17β-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo).</p><p><strong>Results: </strong>A total of 298 women (mean age 60.3 y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (β(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (β(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women ≥65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons.</p><p><strong>Conclusions: </strong>In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the menopause data gap: a scoping review of status, symptoms, and trends in electronic health records.","authors":"Robin R Austin, Malin B Lalich, Meijia Song, Jeana M Holt, Carolyn Gibson","doi":"10.1097/GME.0000000000002868","DOIUrl":"https://doi.org/10.1097/GME.0000000000002868","url":null,"abstract":"<p><strong>Importance and objective: </strong>Gaps in menopause status classification, reproductive stage documentation, and symptom capture (eg, vasomotor symptoms) within electronic clinical information systems, including electronic health records (EHRs), limit clinical care and menopause research. This scoping review examined how menopause-related data are structured and operationalized within EHR systems and identified gaps in documentation that limit clinical care and research.</p><p><strong>Methods: </strong>We searched Ovid MEDLINE, Scopus, CINAHL, and IEEE Xplore (2004 to March 2026) using terms related to menopause, climacteric, perimenopause, and EHR documentation, supplemented by backward citation searching. Two reviewers independently screened studies, with discrepancies resolved by consensus. Quality appraisal was conducted using the Johns Hopkins Evidence-based Practice framework. Rayyan and Excel facilitated article management, data extraction, and synthesis.</p><p><strong>Discussion and conclusion: </strong>Nineteen studies met the inclusion criteria. Most were retrospective cohort or cross-sectional analyses conducted in US health systems (2013-2026), with sample sizes from 45 to 307,512 women. Thirteen studies relied on International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/ICD-10) codes to identify menopause-related experiences; however, only nine reported the codes used. Across studies, three interrelated themes emerged: documentation limitations (including the absence of structured reproductive stage fields and reliance on unstructured text), undertreatment of documented symptoms, and underreporting of menopause-related symptoms in the EHR data. Menopause remains inconsistently represented in EHRs, reflecting structural documentation gaps that constrain longitudinal tracking, clinical decision-making, and research reproducibility. Development of standardized menopause common data elements, including structured stage and symptom documentation, will require coordinated, multidisciplinary efforts to improve data quality and support scalable menopause research.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: association between reproductive span and postmenopausal metabolic syndrome: a cross-sectional study in China.","authors":"Bengü Mutlu Sütcüoğlu, Cemre Karçaaltıncaba","doi":"10.1097/GME.0000000000002858","DOIUrl":"10.1097/GME.0000000000002858","url":null,"abstract":"","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":"33 9","pages":"1034"},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of structured physical activity on body composition and body image perception in postmenopausal women: a systematic review and meta-analysis.","authors":"Federica De Luca, Federica Moro, Luciana Zaccagni, Emanuela Gualdi-Russo, Stefania Toselli, Natascia Rinaldo","doi":"10.1097/GME.0000000000002838","DOIUrl":"https://doi.org/10.1097/GME.0000000000002838","url":null,"abstract":"<p><strong>Importance: </strong>Physical activity (PA) may mitigate adverse changes in body composition (BC) and body image (BI) in postmenopausal women; however, the magnitude and consistency of its effects remain unclear.</p><p><strong>Objective: </strong>To systematically review and synthesize evidence from experimental studies examining the effects of structured PA interventions on BC parameters and BI perception in postmenopausal women (PROSPERO: CRD42024539791).</p><p><strong>Evidence review: </strong>MEDLINE, Web of Science, and Scopus were searched for randomized controlled trials published in English from 2014 to 2025 reporting BC and/or BI outcomes. Risk of bias and certainty of evidence were assessed using the RoB 2.0 tool and the GRADE approach. Pooled mean differences (MDs) with 95% CIs were estimated using a random-effects model for body mass index (BMI), percentage of fat mass (%F), and waist-to-hip ratio (WHR).</p><p><strong>Findings: </strong>After duplicate removal, 2,483 records were screened, and 13 trials involving 694 postmenopausal women met the inclusion criteria. Most studies had a low risk of bias or some concerns. Despite wide variation in frequency, intensity, type, and duration of PA interventions, meta-analyses suggested significant reductions (P < 0.001) in BMI (MD = -0.87 kg/m2; 95% CI: -1.20 to -0.55), %F (standardized MD: -0.53; 95% CI: -0.81 to -0.26), and WHR (MD = -0.03; 95% CI: -0.04 to 0.02). The heterogeneity was low for BMI and WHR (I2 = 0%) and moderate for %F (I2 = 57%) despite considerable within-study variability. Evidence on BI was limited and inconclusive, with only one study reporting preintervention and postintervention data.</p><p><strong>Conclusions and relevance: </strong>Structured PA appears to improve key BC parameters in postmenopausal women. Evidence regarding BI is insufficient, emphasizing the need for rigorous, long-term trials to clarify PA's effects on BI. These findings may guide clinicians in recommending PA for postmenopausal women to improve BC, while highlighting a critical gap in evidence regarding BI.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1, open-label, within-participant dose-escalation study to evaluate the safety and pharmacokinetics of topical sildenafil cream in healthy postmenopausal women.","authors":"Katherine Cornell, Isabella Johnson, Andrea Thurman, David Friend","doi":"10.1097/GME.0000000000002879","DOIUrl":"https://doi.org/10.1097/GME.0000000000002879","url":null,"abstract":"<p><strong>Objectives: </strong>To describe the systemic and local genital safety and pharmacokinetics (PK) of topical sildenafil cream, 3.6% (sildenafil cream) among healthy postmenopausal women.</p><p><strong>Methods: </strong>This was a phase 1, open-label, within-participant, dose-escalation study. Participants (N=21) were exposed to a single dose of placebo cream and three doses of sildenafil cream containing 50, 100, and 200 mg of sildenafil citrate. There was a 14-16-day washout period between each dose. Blood was obtained for analysis of sildenafil and its active metabolite, N-desmethyl sildenafil, plasma levels, before dosing and for up to 32 hours after each dose. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs), vulvar-vaginal irritation scores, electrocardiograms, laboratory testing and orthostatic vital signs.</p><p><strong>Results: </strong>Twenty-one Hispanic women (mean age: 57 y) were enrolled and 19 completed all 4 treatment arms. All doses of sildenafil cream were well tolerated. All TEAEs were mild. There were no cardiac TEAEs or episodes of symptomatic orthostatic hypotension. At the maximum 200 mg dose, the geometric mean (coefficient of variation % [CV%]) maximum plasma concentration (Cmax) of sildenafil was 5,262 (42) pg/mL occurring at 2 hours post-dosing. The Cmax after the 100 mg dose, the dose used in a subsequent phase 2b study in premenopausal women, was 3,810 (41) pg/mL. Both concentrations are ∼2 orders of magnitude lower than those seen in men after a single 100 mg oral dose (450,000 pg/mL).</p><p><strong>Conclusions: </strong>These data support further clinical development of topical sildenafil cream for the treatment of female sexual arousal disorder in postmenopausal women and are consistent with phase 2b data among premenopausal women and their male sexual partners.</p>","PeriodicalId":18435,"journal":{"name":"Menopause: The Journal of The North American Menopause Society","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}