Original research publications

Herlyn-Werner-Wunderlich syndrome, also referred to as obstructed hemivagina with ipsilateral renal agenesis (OHVIRA) is a rare congenital urogenital anomaly resulting from abnormal development of the Müllerian and Wolffian ducts, classically characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. It typically presents after menarche with nonspecific symptoms, often leading to delayed diagnosis and increased risk of complications such as hematometra and pelvic endometriosis. Radiologic imaging plays a key role in early detection and prevention of disease progression. A 16-year-old female presented with progressive dysmenorrhea for 1.5 years and irregular menstruation. Ultrasonography demonstrated uterus didelphys, a left adnexal cyst suggestive of endometrioma, and left renal agenesis. Magnetic resonance imaging (MRI) further delineated a noncommunicating left uterine unit with cervicovaginal atresia and hematometra, consistent with type 1.2 HWWS. MRI also confirmed a left ovarian endometrioma, showing T1 hyperintensity and T2 shading. CT urography further confirmed complete left renal and ureteral agenesis with preserved contralateral renal excretory function, completing the radiologic evaluation of the associated urinary tract anomaly. These multimodality imaging findings established the diagnosis and accurately defined the extent of the congenital anomaly and its associated complications. This case emphasizes the importance of early recognition of Herlyn-Werner-Wunderlich syndrome in adolescents with persistent dysmenorrhea and underscores the pivotal role of imaging. While ultrasonography is useful for initial assessment, MRI remains the gold standard for comprehensive evaluation. Early and accurate diagnosis is essential to guide management and prevent long-term complications, including endometriosis and infertility.

Endometriosis is a chronic estrogen-dependent disorder characterised by the growth of endometrial-like tissues outside the uterus. Recent data suggest a potential role for endometrial stem/progenitor cells in the development of endometriosis. However, evidence on the frequency of various stem cell populations in ectopic lesions and their paired eutopic counterparts remains limited. Hence, this study assessed the frequencies of endometrial stem cells and their characteristics in eutopic and ectopic endometria of women with endometriosis, and also probed whether these attributes differ in women without endometriosis. We analysed the frequencies of endometrial stem cells and their functional properties, isolated from ectopic lesions and paired eutopic endometrium, in women with endometriosis (n = 72) and women without endometriosis (n = 24). Comparative analysis revealed that the eutopic endometrium had a significantly increased frequency of SUSD2+ eMSCs in women with endometriosis than in those without the disease. Immunophenotypic characterisation of SUSD2+ eMSCs using classical MSC markers (CD73, CD90, CD105, and HLA-ABC) revealed that they retained more than 80% positivity in the eutopic endometrium, whereas variable expression of these markers was observed among ectopic lesions. On functional characterisation, the wound healing assay revealed that eMSCs from deep infiltrating endometriosis have increased migratory capacity compared to control and paired eutopic endometrium. Moreover, a preponderance of eEPCs (N-cadherin+ SSEA-1+ and N-cadherin- SSEA-1+) was observed in the eutopic endometrium of endometriosis. In contrast, a significantly increased frequency of Side Population was observed in ectopic lesions compared to eutopic endometrium. Besides Side Population, ovarian endometrioma exhibited a significantly increased frequency of pericyte eMSCs co-expressing CD146 and CD140b. These findings clearly demonstrated a distinct frequency of endometrial stem/progenitor cells in endometriosis. Collectively, this study underscores the predominance of endometrial stem cells and highlights altered immunophenotypic characteristics and enhanced migration capabilities of ectopic eMSCs, possibly driven by unique cellular microenvironments.

Is endometriosis associated with alterations in the intraovarian steroidogenic milieu in women undergoing IVF compared with rigorously matched women without the disease? Prospective cohort study comparing intrafollicular steroid hormone concentrations between women with and without endometriosis undergoing IVF. Eighty-three affected women were recruited and matched 1:1 with controls for age at oocyte retrieval, study period, stimulation regimen and serum anti-Müllerian hormone. Follicular fluid was collected, pooled and stored. Concentrations of 14 steroid hormones were measured using liquid chromatography-tandem mass spectrometry. Subgroup analyses focused on women with ovarian endometriomas and on intra-patient comparisons in cases of unilateral disease. Compared with controls, women with endometriosis showed significantly higher concentrations of 11-deoxycortisol and lower concentrations of aldosterone and progesterone (adjusted P = 0.024 for all). These differences were more pronounced in women with ovarian endometriomas, who also had significantly higher concentrations of corticosterone, dehydroepiandrosterone and testosterone than controls (adjusted P = 0.003, P = 0.011 and P = 0.003, respectively). No significant differences in steroid concentrations were observed between affected and contralateral intact ovaries in women with unilateral endometriomas. The follicular fluid of women with endometriosis has a distinct hormonal profile compared with that of controls, suggesting alterations in steroidogenesis. Reasons explaining these differences, as well as their clinical relevance, remain unknown and deserve further investigations.

This study aimed to define surgical success in patients with endometriosis from a patient-centred perspective and determine the improvement in pain and quality of life that patients consider indicative of a successful surgical outcome. This pilot study included a sample of 36 patients with symptomatic endometriosis and scheduled surgery at Laval University Hospital Center (Québec, Canada), a tertiary referral centre for endometriosis. Patients completed an online survey addressing their definitions of surgical success and surgical failure, as well as their baseline symptoms and the minimal improvement they would expect in various domains related to pain and quality of life. A mixed method combining qualitative and quantitative data was used. Absolute and relative differences between preoperative and expected postoperative scores for each domain were analysed. Ninety-seven percent of patients (n = 35) identified improvement in quality of life as the main determinant of surgical success, whereas no consensus emerged regarding the definition of surgical failure. The mean minimal expected reduction in Endometriosis Health Profile-30 (EHP-30) score was 34 points (95% CI 26.7-40.4; P < 0.001). Most patients (91.7%) expected a postoperative EHP-30 score below 40, regardless of their baseline score. Overall, patients expected a 52%-69% reduction in pain symptom scores. The most important patient-reported outcome defining surgical success was improvement in quality of life, with the majority of patients aiming for an EHP-30 score below 40 after surgery. The use of a defined threshold may help establish a standardized definition of surgical success in future clinical practice and research on endometriosis.

Endometriosis is a widespread gynecological disorder causing severe pain and infertility, with diagnosis currently relying on slow, costly, and risky laparoscopy. This highlights the critical need for non-invasive imaging diagnostics using transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). A key challenge is that patients typically receive only one scan modality in practice, despite TVUS and MRI offering differing diagnostic strengths for endometriosis signs like Pouch of Douglas (POD) obliteration and bowel nodules (BN). Previous work partially addressed this challenge by leveraging unpaired multi-modal data for detecting a single marker: Pouch of Douglas (POD) obliteration. However, this is restrictive because endometriosis signs, such as POD obliteration and bowel nodules (BN), often provide correlated diagnostic cues. Capturing these correlations is essential for accurate detection of endometriosis imaging signs, particularly when combined with multi-modal learning, as each modality offers complementary strengths for different signs. To overcome these limitations, we propose EndoFusion, a novel unpaired multi-modal, multi-label learning framework that enables the detection of POD and BN from TVUS and MRI. Our approach introduces three key innovations: (1) label-based pairing, mixup, and cross-modal feature exchange for robust single-modality inference; (2) Dynamic Mutual Knowledge Distillation (DMKD), which adaptively selects teachers using a worst-student-oriented strategy for effective cross-modal transfer; and (3) label correlations modeling with multi-head attention and a specialized loss to handle imbalance and boost accuracy. This design ensures that knowledge from the superior modality and from co-occurring signs is effectively transferred, mitigating modality-specific weaknesses and improving robustness in imaging sign detection. Experiments on our endometriosis dataset show that our method significantly outperforms all comparison methods, achieving an average AUC of 0.827 (95% CI: 0.790-0.861) when evaluated using single-modality inference. These results represent an initial proof-of-concept toward multi-modal, non-invasive assessment of selected endometriosis imaging signs from MRI and TVUS.

To evaluate the clinical impact of incorporating patient-specific 3-dimensional (3D) printed anatomical models into gynaecologic practice for improving surgical planning and patient outcomes in patients with deep endometriosis. A pilot prospective randomized controlled study using a repeated-measures, questionnaire-based design included patients who consented to surgical excision of endometriosis. Patients were randomized to have a 3D printed model or not (control). 3D models were rendered from T2-weighted magnetic resonance images. Gynaecologic surgeons completed questionnaires on surgical planning, surgical outcomes and surgeon experience before and after viewing the 3D printed models and postoperatively, and comparisons were made using paired t tests. There were 5 patients included in the 3D printing group and 8 patients in the control group. In the 3D printing group, there was a change in 5/10 (50%) surgeon responses for perception of surgical level of difficulty, 5/10 (50%) surgeon responses for allotted surgical time, and 3/10 (30%) surgeon responses for estimated blood loss after viewing the 3D model. Eight of 10 (80%) surgeon responses indicated that the model was referenced intraoperatively. Allotted surgical time was significantly greater post-viewing compared to pre-viewing the model (256.4 ± 60.5 vs. 246.4 ± 56.6 minutes; d = -0.19, P = 0.044) and estimated blood loss significantly lower post-viewing compared to pre-viewing the model (177.3 ± 114.8 vs. 204.6 ± 154.1 mL; d = 0.293, P = 0.003). Compared to control cases, mean surgical time was significantly lower in the 3D model cases (271.7 ± 94.6 vs. 460 ± 225.2 minutes; P = 0.006). 3D printed models may help to optimize surgical planning and improve surgical performance, bettering the overall surgical outcomes in gynaecologic surgery for deep endometriosis.

Previous studies have suggested the close link between endometriosis and body size index. However, there are inconsistent associations between central, general, and visceral adiposity index and endometriosis. This study aimed to evaluate and compare trend of general, central, and visceral adiposity indices in women with and without endometriosis using longitudinal population-based data. We analyzed data from 3159 premenopausal women aged 20-45 years with defined status of endometriosis who participated in the TLGS from phases 3 to 7. The interval between phases was 3 years. Adiposity indices including general (body mass index), abdominal (waist circumference, waist-to-hip ratio, waist-to-height ratio) and visceral (lipid accumulation product, a body shape index, body roundness index, and visceral adiposity index) were evaluated. Generalized Estimating Equations were used to examine longitudinal trends and associations of endometriosis status with adiposity indices, adjusting for age, parity, smoking, education, and physical activity. Among the participants, 421 women (13.3%) had diagnosed endometriosis. All adiposity indices showed significant increasing trends over time in both groups. Endometriosis status was not significantly associated with general or central adiposity indices. However, among visceral adiposity measures, the visceral adiposity index was consistently higher in women with endometriosis (adjusted difference: 0.56; 95% CI: 0.10-1.03; p = 0.016), indicating greater visceral fat accumulation. This study is the first to use longitudinal population-based data to simultaneously evaluate general, central, and visceral adiposity indices in women with endometriosis. Findings indicate that visceral adiposity, rather than general or central obesity, may represent a metabolically relevant phenotype.

To assess the preoperative diagnostic accuracy of abdominal wall endometriosis (AWE) by general surgical teams and specialized endometriosis centers in assessing abdominal wall masses using clinical evaluation and imaging. A retrospective cohort study included patients with a pathologic diagnosis of AWE who underwent surgical excision between 2007 and 2022. Patients treated by specialized endometriosis surgeons were compared with those treated by general surgery teams. Data collected included patient demographics, lesion size, preoperative symptoms, diagnostic modalities, and surgical outcomes. Statistical analysis was conducted using univariant and multivariable regression models to identify factors associated with misdiagnosis. Correlation between the size of lesion and the need for the use of mesh was also done. A total of 46 patients with AWE were included; 27 (58.7%) were treated by the specialized endometriosis center and 19 (41.3%) by general surgeons. Evaluation by a specialized endometriosis center demonstrated a significantly higher correct diagnosis rate compared to the general surgery group (96.3% vs 42.1%, P < 0.001), with no significant difference in complication rates. Regression model revealed that admission by general surgeons increased the likelihood of misdiagnosis by 28 times (28.01 95% confidence interval [CI]: 2.74-286.47, P = 0.005). Computed tomography (CT) and magnetic resonance imaging were used more frequently in the general surgery group 42.1% versus 3.7%, P = 0.001. Endometriosis ultrasound was used more frequently in the specialized endometriosis group (100% vs 0%, P < 0.001). Independent of the group the probability of mesh use increased markedly for lesions larger than 3 cm with near certainty for lesions larger than 5 cm. Evaluation by specialized endometriosis surgeons was associated with significantly higher diagnostic accuracy of AWE detection compared with evaluation by general surgical teams. Early referral to experienced endometriosis units may reduce misdiagnosis and improve surgical planning.

Endometriosis is associated with neuropathic pain in approximately 40% of cases. Involvement of the sciatic nerve or sacral plexus represents one of the most frequently reported neuropathic pain presentations in endometriosis, for which no specific management guidelines currently exist. This study evaluate the efficacy and safety of laparoscopic decompression of the sciatic nerve or the sacral plexus for neuropathic sciatic pain caused by endometriosis. A systematic search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for studies published between 2000 and 2025. Eligible studies included interventional and observational studies reporting outcomes in women undergoing laparoscopic decompression for neuropathic pain located along the sciatic nerve distribution due to endometriosis involving the sciatic nerve and/or the sacral plexus. Data extraction was performed independently by two reviewers. W le, a random-effects meta-analysis was conducted. The primary outcome was the variation of sciatic pain intensity from baseline to postoperative follow-up, assessed at least 3 months after surgery using validated pain scales. Risk of bias was evaluated using the Joanna Briggs Institute critical appraisal checklists. The search identified 933 records, of which eight studies were included in the final analysis, comprising 744 individuals. Preoperative sciatica attributable to endometriosis was reported in 83.2% of cases (n = 619). Operative findings revealed sciatic nerve involvement in 52.3% of cases (n = 389) and sacral nerve root involvement in 45.0% (n = 335). In a minority of individuals, involvement of other pelvic nerves was also reported. Across five studies with extractable pain-intensity data (n = 520), the pooled mean reduction in sciatic pain was 6.47 points (95% confidence interval 5.55-7.43) on validated 10-point scales. Complete resolution of neuropathic symptoms in the lower limb was reported in a subset of individuals. Major complications occurred in 8% of cases and were mainly associated with concomitant pelvic procedures. Laparoscopic nerve decompression appears to be associated with a clinically significant reduction in neuropathic sciatic pain related to endometriosis, with a low incidence of major nerve-related complications. However, as the available evidence is predominantly observational and characterized by a low to moderate risk of bias, these findings should be interpreted with caution and highlight the need for further well-designed studies. The study protocol was prospectively registered in PROSPERO (CRD420251107880) on July 19, 2025.

To evaluate how oophorectomy during a hysterectomy for endometriosis impacts reoperation rates and pain-related healthcare services in a cohort of histopathologically confirmed endometriosis cases. In this population-based retrospective cohort study, we included 990 cases of pathologically confirmed endometriosis in people aged 19-50 years who underwent hysterectomy between 2001 and 2016. The primary outcome was reoperation, and secondary outcomes included physician visits as well as filling prescriptions for opioids, oral contraceptive pills (OCP), and endometriosis medications within the 3-12 months after surgery. Kaplan-Meier curves and Cox proportional hazards were used. Compared to hysterectomy with ovarian conservation, hysterectomy with oophorectomy was associated with lower rates of reoperations (19.2% for hysterectomy with ovarian conservation vs 13.2% for hysterectomy with unilateral salpingo-oophorectomy and 4.9% for hysterectomy with bilateral salpingo-oophorectomy; aHR= 0.56, 95%CI= (0.36-0.88) and aHR= 0.20, 95%CI= (0.12-0.35), respectively). Pelvic peritoneal adhesions, recurrence of endometriosis, and endometrioma were the most common reasons for reoperations. No differences were observed between ovarian conservation versus bilateral oophorectomy in terms of physician visits, as well as opioid, OCP, and endometriosis medication dispensations within three to 12 months after surgery. HRT was filled in only 67.2% of those who entered premature surgical menopause CONCLUSION: Undergoing hysterectomy with bilateral salpingo-oophorectomy resulted in a lower rate of reoperation in this cohort of pathologically confirmed endometriosis patients. However, the number of physician visits for endometriosis or pelvic pain, or the rate of pain medication prescriptions, did not suggest an improvement for those who underwent hysterectomy with bilateral salpingo-oophorectomy.

Endometriosis, the second most common gynecological disease, can result in reductions of quality of life and high rates of depressive and anxiety symptoms. Understanding treatment-use patterns and associations with psychological burden may help identify gaps in care. We aimed to describe depressive symptoms, mental disorders, and treatment use and explore associations with endometriosis-related quality of life in individuals with endometriosis interested in an online cognitive behavioral therapy program. Three hundred twenty‑nine participants completed an online survey assessing treatments used, quality of life (Endometriosis Health Profile-30+23), and psychological symptoms (Beck Depression Inventory-II, Web Screening Questionnaire). Of 322 participants, 26.4 percent ( n = 85) had never used hormonal therapy. Moderate to severe depressive symptoms were reported by 46.2 percent ( n = 152). Additionally, 265 participants completed the Structured Clinical Interview-I for DSM-IV, where 27.5 percent ( n = 73) met criteria for a mental disorder, most commonly depressive disorders (14 percent, n = 37). An exploratory multivariate multiple regression showed that a greater treatment count was associated with greater pain-related impairment ( B = 2.06, adjusted R 2 = .05, Holm-adjusted p < .001) and control/powerlessness ( B = 2.24, adjusted R 2 = .05, Holm-adjusted p < .001). These findings support integrated, patient-centered biopsychosocial care that combines medical with psychological interventions.

Heavy menstrual bleeding (HMB) affects up to one-third of reproductive-age women and remains a major cause of gynecologic consultations and impaired quality of life. While some cases are attributable to structural uterine abnormalities, many occur without identifiable pathology, and the mechanisms regulating menstrual blood loss remain incompletely understood. Emerging evidence suggests that menstrual hemostasis depends on coordinated local vascular and hemostatic processes within the endometrium, including spiral artery remodeling, vasoconstriction, transient hemostatic plug formation, and tightly regulated coagulation and fibrinolysis. Disruption of these mechanisms, through abnormal vessel remodeling, impaired thrombus formation, or excessive fibrinolytic activity, may contribute to excessive bleeding. In this review, we synthesize current evidence on endometrial vascular biology and hemostatic regulation during menstruation and propose a hypothetical, multiphase biomechanical framework, yet to be validated, in which permissive fibrinolysis, nonocclusive coagulation clots, vasoconstriction, and occlusive shear-induced platelet aggregation successively dominate menstrual hemostasis. Within this framework, unexplained HMB is hypothesized to arise when impaired spiral artery vasoconstriction prevents local wall shear from reaching the range that supports mechanically robust, platelet-rich occlusion. Although this proposed framework is intended as a testable hypothesis, it generates specific, falsifiable predictions and identifies measurements needed to evaluate it. By highlighting key knowledge gaps in the control of menstrual hemostasis, this work aims to guide future research toward mechanism-based, fertility-preserving therapies for women with HMB.

To evaluate whether a patient-centered integrated menopause clinic model was associated with menopausal hormone therapy initiation, self-reported medication habits, and menopause-related knowledge among women with indications for treatment. We retrospectively analyzed 405 women aged 40-60 years with MHT indications who attended Peking University First Hospital in 2023. Outcomes were compared between the MHT Integrated and Patient-Centered Clinic (MIPCC; n = 192) and a general menopause clinic (GMC; n = 213) after one year. MIPCC patients were slightly older and more often postmenopausal. Insomnia, reduced libido, dyspareunia, vaginal dryness, and recurrent vaginitis were more frequent in the MIPCC group. MHT initiation was higher in the MIPCC group than in the GMC group (165/192 [85.94%] vs. 94/213 [44.13%]; adjusted OR 7.60, 95% CI 4.63, 12.49). Discontinuation among initiators was numerically lower in the MIPCC group (18.29% vs. 20.21%), but no statistically significant difference was observed. Selected self-reported medication-habit and knowledge responses were more favorable among MIPCC patients. The MIPCC model was associated with higher MHT initiation and more favorable responses to selected self-reported medication-habit and knowledge items. Patient-centered menopause management may represent a useful preventive health strategy, but prospective multicenter studies are needed to confirm its effectiveness and generalizability.

To provide evidence-based recommendations for the management of vasomotor, sleep, and mood symptoms related to spontaneous menopause and induced menopause (at or beyond age 40 years). Perimenopausal and postmenopausal individuals assigned female sex at birth (ie, women, transgender men, and gender-diverse individuals) with vasomotor, sleep, and mood symptoms related to spontaneous or induced menopause. This guideline was developed using an a priori protocol in conjunction with a writing team consisting of a subspecialist in reproductive endocrinology and infertility, a Menopause Society Certified Practitioner and subspecialist in reproductive endocrinology and infertility, and a specialist in obstetrics and gynecology. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements. This Clinical Practice Guideline includes recommendations on pharmacologic and nonpharmacologic interventions for the management of menopause-related vasomotor, sleep, and mood symptoms. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide clinical guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence.

Alterations to the vaginal microbiota have been investigated in genitourinary syndrome of menopause but data regarding periurethral and urinary microbiota remain limited. We aimed to characterize vaginal, periurethral, and urinary microbiota in clinically stratified postmenopausal women and to evaluate the effects of estrogen therapy. In this prospective study, postmenopausal women were categorized as controls without atrophy or symptoms, women with clinical atrophy without symptoms, symptomatic women, and symptomatic women receiving 12 weeks of vaginal estriol. Vaginal, periurethral, and bladder samples were collected. Microbiota composition and diversity (alpha diversity - Shannon index; and beta diversity - Bray-Curtis dissimilarity) across urogenital niches and changes in these following estrogen therapy. Vaginal and periurethral alpha diversity was higher in women with asymptomatic atrophy and symptomatic women at baseline than in controls and estrogen-treated women. Beta diversity analyses demonstrated separation of controls and estrogen-treated women from the atrophy groups at baseline. Controls exhibited Lactobacillus-enriched periurethral communities and Klebsiella-dominant urinary profiles. Women with asymptomatic atrophy and symptomatic women showed reduced Lactobacillus and increased anaerobic taxa in vaginal and periurethral niches, while urinary samples were characterized by Escherichia predominance. Notably, in women with asymptomatic atrophy, Lactobacillus abundance was higher in periurethral than vaginal samples. Estrogen therapy increased Lactobacillus abundance in vaginal and periurethral compartments and shifted urinary microbiota toward a control-like composition. Periurethral Streptococcus abundance correlated with sexual symptom scores. Microbial alterations in genitourinary syndrome of menopause are compartment-specific and extend beyond the vagina. Periurethral microbiota may contribute to symptom expression, while local estrogen therapy promotes restoration of Lactobacillus-dominant urogenital microbiota. gov registration: NCT06633705.

To develop and validate the Menopause Impact Scale (MIS), a brief, person-centered measure of menopause-related symptom impact that is psychometrically robust across reproductive stages and suitable for digital implementation. Three sequential online studies with women aged 21-85 years in the United States (total N = 2915). Study 1 (n = 486) evaluated a 57-item pool using exploratory factor analysis (EFA) and reliability indices. Study 2 (n = 1429) used confirmatory factor analysis (CFA) and item reduction to derive a brief scale. Study 3 (n = 1000) cross-validated the final structure and examined convergent and divergent validity, age sensitivity, and menopause etiology differences. MIS total and subscale scores; structural fit indices; internal consistency; convergent validity with the Greene Climacteric Scale; divergent validity with the Copenhagen Burnout Inventory; age group and menopause etiology differences in symptom burden. EFA supported a seven-factor solution (Kaiser-Meyer-Olkin measure of sampling adequacy [KMO] = 0.968; root-mean-square error of approximation [RMSEA] = 0.048; Cronbach's α = 0.974). A 22-item model showed excellent fit in Study 2 (comparative fit index [CFI] = 0.970; RMSEA = 0.047; α = 0.964) and was confirmed in Study 3 (CFI = 0.977; RMSEA = 0.041; α = 0.941), capturing cognitive, self-perception, sexual/vaginal, musculoskeletal, vasomotor, sleep, and urinary domains. Convergent validity with the Greene total score was strong (r = 0.76); divergent validity with burnout was moderate (r = 0.57). MIS scores peaked in midlife (45-55 years). After age adjustment, symptom burden was highest in primary ovarian insufficiency, with the largest differences in vasomotor and genitourinary domains. The MIS is a brief, multidimensional, impact-focused instrument with strong structural, convergent, and discriminant validity, supporting research, clinical, and digital applications.

In humans, menopause is associated with a suppression of resting metabolic rate (RMR), accelerated adipose gains, and increased risk of cardiometabolic disease. Mechanistic dissection of the changes in RMR control across the menopause transition is difficult because rodent models do not naturally undergo menopause. Although rodents lack a natural menopause, chemical treatment with 4-vinylcyclohexene diepoxide (VCD) induces progressive ovarian failure, paralleling the complex hormonal alterations across perimenopause and menopause that occur in humans. To explore the impact of diet upon cardiometabolic phenotype development in this experimental model of menopause, young adult (10-12 wk old) female C57BL/6J mice were fed either PicoLab 5L0D (corn/soy-based, phytoestrogen-containing) or Inotiv 2920x (wheat/corn-based, phytoestrogen-free) diets and treated with VCD (160 mg/kg/day for 20 days) or sesame oil vehicle. In mice fed 5L0D, VCD caused a reduction in RMR and thereby total energy expenditure, which was followed by exaggerated adipose gains, despite no changes in food intake. In contrast, in mice fed 2920x, VCD modestly suppressed activity-dependent expenditure but had no effects on RMR, food intake, or adiposity. VCD had no significant modulatory effects upon sodium intake behaviors, digestive efficiency, or endothelial-dependent vascular relaxation in mice fed either diet, though diet alone did influence these end points. Together, these findings demonstrate that diet composition significantly modifies the development of cardiometabolic phenotypes in the VCD rodent model of menopause. Future studies utilizing VCD-induced ovarian failure in rodents to model menopause must carefully consider the modulatory effect of diet formulation upon phenotype development, and thereby the translational relevance of results. NEW & NOTEWORTHY This study demonstrates that the metabolic phenotypes induced by 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure in rodents, used as an experimental model of menopause, strongly depend upon diet formulation. VCD-treated mice fed a corn/soy-based diet (PicoLab 5L0D) exhibited suppressed resting and total energy expenditures and increased adiposity, which parallels effects of menopause documented in humans. In contrast, VCD failed to induce such phenotypes in mice fed a wheat/corn-based diet (Inotiv 2920x).

Physical activity (PA) is frequently promoted as a means of managing symptoms associated with the menopause transition (MT), yet little is known of how the embodied, emotional and temporal disruptions of menopause influence the experiences of, and possibilities for, movement. Taking inspiration from French sociologist Henri Lefebvre's theory of 'rhythmanalysis' and Jennifer Mason's facet methodology approach, we draw on qualitative survey responses from 249 women to examine how symptoms associated with the MT interrelate with space and time to shape everyday experiences of PA. Our findings highlight how symptoms intertwine with seasonal, hormonal and circadian cycles to reconfigure everyday tempos of energy, rest and aspirations to move more. These shifting rhythms often constrain participation in PA, but also prompt creative adjustments including new pacing strategies, altered routines and re-attunements to bodily fluctuation. Our rhythmanalytic approach challenges binary framings of PA as either hindered or facilitated, offering instead a textured account of how movement, stillness and slowing are negotiated during the MT. These original insights contribute to embodied and critical perspectives on health, demonstrating the value of more flexible, rhythmic and context-sensitive approaches to promoting movement through the MT.

Polycystic ovary syndrome (PCOS) has recently been renamed polyendocrine metabolic ovarian syndrome (PMOS). This change is particularly relevant after menopause, when menstrual dysfunction and ovarian morphology are no longer useful for assessment, while cardiometabolic and other long-term health risks remain clinically significant. To review the implications of the shift in terminology from PCOS to PMOS for women in the menopausal transition and after menopause and to provide guidance for assessment and management. This EMAS Clinical Guide is based on a narrative review and expert consensus. PubMed and Web of Science were searched in June 2026 for evidence on PCOS/PMOS during and after menopause, with additional references identified from key guidelines and publications. International guidelines, position statements, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and other clinically relevant publications were considered. There were notable evidence gaps in relation to postmenopausal women. The proposed change from PCOS to PMOS reflects a broader understanding of the condition as a lifelong endocrine and metabolic disorder rather than a syndrome defined mainly by reproductive features and ovarian morphology. After menopause, given that current menstrual and ovarian morphology cannot be used to establish the diagnosis de novo, recognition of PMOS should rely primarily on a documented diagnosis before menopause or a well-characterized reproductive history consistent with the syndrome. Women with PMOS have increased risk of cardiometabolic conditions, including obesity, impaired glucose metabolism, type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. Although evidence specifically in postmenopausal women remains limited, these risks remain clinically relevant during the menopausal transition and after menopause and should be considered during long-term follow-up. Clinical care should focus on cardiometabolic risk assessment, which should include evaluation of body weight, waist circumference, blood pressure, glycemic status, lipid profile, and other established cardiovascular risk factors. New, severe, or rapidly progressive hyperandrogenism after menopause should not be attributed to PMOS without further evaluation for alternative causes. Current evidence does not support additional endometrial, breast, or ovarian cancer screening or a separate osteoporosis screening strategy solely on the basis of PMOS. PMOS alone is not a contraindication to menopausal hormone therapy. Evidence specifically evaluating menopausal hormone therapy in women with PMOS is limited. Current recommendations are largely extrapolated from evidence and guidance for the general menopausal population. The decision to initiate menopausal hormone treatment and the choice of regimen and route should follow standard menopause guidance and be based on symptoms and the woman's overall individual risk.

Women with intellectual disabilities experience significantly poorer health outcomes than women from the general population, on average dying 15 years younger. Little is known about menopause in women with intellectual disabilities; therefore, this study explores the perceptions, experiences and knowledge of women with intellectual disabilities on the topic of menopause. Semi-structured interviews were utilised to collect qualitative data on menopause from women with intellectual disabilities. A sample of 13 women with mild or moderate intellectual disabilities over the age of 35 were purposively recruited from a linked service provider. Reflexive thematic analysis was utilised to generate themes reflecting the perceptions and experiences of participants on the topic of menopause. Ethical approval was obtained for the current study, and Patient and Public Involvement was embedded throughout. Five overarching themes were developed: a) Menopause takes control; b) Difficult to understand; c) Knowledge is power; d) Dismissed due to intellectual disability; e) A tailored approach. The findings indicate a dearth of knowledge among women with intellectual disabilities on the topic of menopause. The lack of understanding is pervasive and influences perceptions of menopause which can negatively affect the severity of menopausal symptoms and help-seeking behaviour. Understanding obtained from an in-depth exploration of menopause highlights the inequities faced by women with intellectual disabilities and can help to inform the production of specialised educational materials, care pathways and tailored policy initiatives on menopause to improve the health outcomes of this population.

Cardiovascular disease (CVD) remains the leading cause of death among women, yet CVD risk is frequently underrecognized during midlife, when the menopause transition is accompanied by significant biological changes. Emerging evidence demonstrates that menopause represents a critical window for adverse cardiometabolic and vascular changes that extend beyond the effects of chronologic aging alone. Because obstetrician-gynecologists often serve as the primary clinicians for midlife care in women, they are uniquely positioned to recognize emerging cardiovascular risk, implement preventive strategies, and coordinate care with primary care or cardiology when appropriate. This Clinical Expert Series synthesizes current evidence on menopause-related characteristics associated with CVD risk, including timing and type of menopause, as well as menopause-related symptoms, including vasomotor symptoms, sleep disturbances, and depression. We also review longitudinal data characterizing changes in lipids, blood pressure, glucose metabolism, body composition, and vascular structure and function across the menopause transition. Collectively, these data support framing menopause as a key opportunity for CVD risk identification and early intervention. Incorporating menopause-specific factors into routine CVD risk assessment may enable earlier prevention strategies and ultimately improve long-term cardiovascular outcomes for women.

This clinical perspective examines how social determinants of health (SDoH) such as economic stability, education and health literacy, health care access and quality, and social and community contexts shape menopause experiences and outcomes through a health equity lens. Menopause is not experienced uniformly: Black, immigrant, and LGBTQ+ (lesbian, gay, bisexual, transgender, queer+) individuals and those with low income often face earlier symptom onset, greater symptom burden, and reduced access to evidence-based care due to structural inequities, economic barriers, and cultural stigma. Menopause care must move beyond a purely biological model to incorporate the social, economic, and cultural realities that influence symptom recognition, treatment access, and long-term health. Integrating SDoH screening, expanding inclusive research, and advancing culturally responsive, trauma-informed, person-centered care are essential to improving menopause outcomes and promoting equitable healthy aging.

To assess the midlife and menopause experiences and unmet health needs of servicewomen and veterans. For this qualitative study, we conducted virtual focus groups with servicewomen and veterans aged 45-60 years using a semi-structured, open-ended interview guide focused on midlife and menopause experiences and related health care access. Focus groups were held from June to August 2025 until thematic saturation was met. Transcripts were coded and thematic analysis performed using Atlas.ti software. We conducted five focus groups with 30 participants (mean age 51.5 years; 53.3% active duty). Participants received health care across the Military Health System, Veterans Health Administration (VHA), and private sector. Four categories emerged: effects on personal life, menopause-related care delivery, effects on military and professional career, and recommendations for improvements. Within these categories, seven themes were identified: feeling unprepared and navigating menopause independently, effects on relationships, frustration with care delivery, positive care delivery experiences, effects on military performance and readiness, unique military settings complicating symptoms and treatment, and recommendations to improve menopause experiences and care delivery in the military. Frustration with care delivery included feeling dismissed, symptom misattribution or treatment of individual symptoms, lack of menopause knowledge among clinicians, inconsistent access to knowledgeable clinicians, and seeking care outside the Military Health System or VHA. Positive care experiences included symptom validation, provision of treatment, and continuity of care. Menopause symptoms substantially affect quality of life and occupational functioning among servicewomen and veterans, with system-level gaps in menopause care overshadowing positive experiences. Findings highlight deficiencies in anticipatory guidance, workplace support, clinician education, access to care, and continuity of care across health systems. Targeted interventions to improve workplace culture surrounding menopause, menopause-specific clinical competency, and access to evidence-based care are needed to support quality of life and maintain military readiness.

Menopause care in the United States is limited by inadequate access, insufficient clinician training, and the absence of scalable care models. Despite increasing awareness and intolerance of menopause symptoms, few health systems offer coordinated menopause services, and no published frameworks exist to guide program development. We present a practical, evidence-informed flexible nine-step blueprint for designing, implementing, and sustaining comprehensive menopause programs, including a structured needs assessment and a resource-tiered implementation framework for program development. Drawing on implementation science, multidisciplinary care models, and the authors' real-world experience from large academic health systems, we describe each of the essential steps. This approach provides practical strategies for developing standardized clinical workflows, scalable care pathways, and workforce capacity. Case examples demonstrate stepwise adoption across diverse settings, beginning with foundational activities and expanding as resources grow. This blueprint offers a scalable approach to addressing persistent gaps in women's health for midlife and beyond.

Breast cancer survivors (BCSs) receiving endocrine therapy frequently develop genitourinary syndrome of menopause, characterized by vaginal dryness, pain, and urinary symptoms. Fractional CO 2 vaginal laser therapy has been proposed as a non-hormonal management option, but the optimal number of treatment sessions remains unclear. As preparation for a forthcoming randomized, blinded, sham-controlled trial, this dose-determining study evaluated how the number of fractional CO 2 laser sessions influences urogenital symptoms and objective vaginal parameters to identify session-dependent dose-response patterns. This single-center dose-determining study was conducted at Randers Regional Hospital, Denmark. Thirty BCSs on endocrine therapy with symptomatic genitourinary syndrome of menopause underwent five monthly sessions of fractional microablative CO 2 vaginal laser using a standardized intravaginal probe protocol. Outcomes were evaluated at baseline and 4 weeks after the third, fourth, and fifth sessions. The primary outcome was vaginal dryness (VAS 0-10). Secondary outcomes included vaginal pain, itching, and soreness (VAS); sexual function (FSFI, SCS-W); urinary symptoms (UDI-6, ICIQ-FLUTSsex); and vaginal health (VHI). Statistical analyses involved paired within-participant comparisons across time points. Twenty-seven participants (90%) completed all five sessions. Vaginal dryness decreased significantly after three treatments, with a further incremental reduction by the fifth, representing the largest session-dependent change. FSFI scores increased significantly from baseline, with additional improvements across later sessions. SCS-W and ICIQ-FLUTSsex scores decreased steadily, while UDI-6 improved from baseline but remained stable across subsequent assessments. Treatments were well tolerated, with no serious adverse events. Fractional CO 2 vaginal laser therapy demonstrated incremental, session-dependent changes in urogenital symptoms and vaginal health measures, with the greatest improvements after five sessions. The protocol was feasible and acceptable for BCSs receiving endocrine therapy. Overall, these findings provide clinically relevant dose-response insight to help guide optimization of treatment parameters ahead of future randomized, sham-controlled trials overall.

Women transitioning through menopause are often affected by vasomotor symptoms (VMS), bone loss, metabolic dysfunction, and increased cardiovascular risk. Although menopausal hormone therapy remains the most effective treatment for menopause, nonhormonal strategies are essential for women with contraindications, personal preference, or a history of hormone-sensitive cancers. This narrative review evaluates evidence-based integrative approaches to menopause care, including lifestyle interventions, mind-body therapies, nutritional strategies, botanicals, and complementary modalities. Cognitive behavioral therapy and clinical hypnosis have been shown to significantly reduce vasomotor symptom distress and are recommended as nonhormonal options. Although mindfulness-based interventions may improve sleep and quality of life (QOL), they are not recommended for the relief of VMS. Regular physical activity and dietary optimization are foundational for bone health and improving metabolic risk factors. Acupuncture may provide subjective improvements in overall symptom burden and QOL for some individuals. Despite the common use of phytoestrogens and various botanical therapies, high-quality evidence supporting their efficacy for VMS remains inconsistent. Consequently, these modalities are not advised for routine symptom management, particularly given their lack of standardization and potential safety concerns. Integrative approaches should be incorporated as part of an individualized, patient-centered care plan. Further research is needed to clarify effectiveness, safety, and optimal integration of these treatment approaches into clinical practice.

This Narrative Review provides a practical, symptom-based framework for the management of menopause in patients with cancer, emphasizing risk stratification and collaboration with oncology. Current evidence and guideline recommendations were synthesized from randomized trials, observational studies, systematic reviews, and major society position statements, with findings organized by symptom domain and stratified by cancer type and hormone sensitivity to support clinical decision making. Menopausal symptoms are common and often severe in patients undergoing cancer treatment, particularly in those with treatment-induced menopause, and management requires balancing symptom relief with oncologic safety. Nonhormonal therapies are first-line treatment across cancer types, with strong evidence supporting selective serotonin and norepinephrine reuptake inhibitors, gabapentin, and lifestyle interventions for vasomotor symptoms. Vaginal estrogen is effective for genitourinary syndrome of menopause, is appropriate in most gynecologic cancers, and may be considered in select breast cancer survivors after shared decision making. Systemic hormone therapy remains contraindicated in hormone receptor-positive breast cancer but may be considered in carefully selected patients with non-hormone-dependent malignancies or low-risk gynecologic cancers. Nonhormonal considerations-including thrombotic risk, hepatic function, drug-drug interactions, and cardiometabolic health-are critical to safe management. A symptom-based, risk-stratified approach enables gynecologists to manage menopause in patients with cancer through collaboration with oncology, supporting individualized care and improved quality of life.

Age-associated estrogens decline is increasingly recognized as a systemic driver of neurodegeneration, yet the mechanisms by which estrogen deficiency alters neuronal resilience remain incompletely understood. Here, we investigated how mimicking age-related endocrine decline influences the susceptibility of retinal neurons to ischemic stress and whether simultaneous targeting of survival and apoptotic pathways restores neuronal resilience. Using a mouse model of surgical menopause (total N = 62 divided into groups containing 4-6 specimen), we demonstrate that estrogen deficiency markedly exacerbates retinal ganglion cell (RGC) loss by approximately 60% and severely impairs functional recovery following ischemia-reperfusion injury. Pharmacological modulation revealed that selective estrogen receptor signaling or Fas pathway inhibition alone provided partial neuroprotection. However, combined treatment with the selective estrogen receptor modulator Raloxifene and the Fas receptor antagonist KP7-6 produced a powerful synergistic effect, limiting RGC somatic loss to a mere 18% and restoring stratified retinal function to near-physiological levels in both ovariectomized and non-ovariectomized animals. Ex vivo retinal explants (N = 15) confirmed that dual pathway modulation drives a 2-fold increase in neuronal survival and significantly limits cytotoxicity, supporting a direct cellular mechanism. These findings identify endocrine aging as a modifiable driver of neuronal vulnerability and demonstrate that simultaneous targeting of estrogen-dependent survival signaling, and Fas-mediated apoptosis can restore a youthful neuroprotective phenotype. Our results establish convergent hormonal and apoptotic pathways as one of regulators of neuronal resilience during aging and suggest a combinatorial therapeutic strategy for age-related neurodegenerative disorders.