Introduction On average, women now spend more than one-third of their lives in the post-reproductive period, yet menopause care across Europe remains fragmented and uneven. Since the first publication of its model of care by the European Menopause and Andropause Society (EMAS) in 2016, major advances in precision medicine, digital phenotyping, biomarkers derived from data collected by wearable devices, artificial intelligence, hybrid care delivery, and workplace health have reshaped clinical opportunities and societal expectations. At the same time, population aging, rising multimorbidity, and increasing public and employer awareness position menopause as a public health inflection point rather than a narrow reproductive transition. Aim This updated EMAS Position Statement, ‘Healthy Menopause’, sets out a future-oriented framework for the coming decade. Materials and methods This Position Statement was developed through iterative consultation and consensus among the authors, informed by current evidence, existing clinical guidance, and relevant regulatory frameworks. Results and conclusions The framework integrates risk stratification, validated digital tools, and clinical decision support. It also structures menopause healthcare considerations into a scalable tiered care architecture comprising digital access, trained menopause healthcare professionals, multidisciplinary specialist centers, and a supportive policy and governance environment. It provides actionable recommendations for clinicians, health systems, professional societies, employers, and researchers, including on competency-based training and accreditation, quality standards, governance requirements for digital health and artificial intelligence, and mechanisms to monitor outcomes and equity. By linking clinical innovation, digital ecosystems, and societal determinants, this Position Statement outlines a blueprint for equitable, preventive, and personalized menopause care across Europe.

PURPOSE:Ductal carcinoma in situ (DCIS) is a non-invasive precursor of invasive breast cancer and is primarily treated surgically. Re-excision is commonly performed to achieve clear margins; however, its impact on local recurrence remains controversial. This study evaluated whether re-excision influences the risk of ipsilateral breast tumor recurrence in patients with DCIS. METHODS:In this retrospective single-center cohort study, all patients treated for DCIS at the University Hospital Münster between 2003 and 2015 were included. Clinical and pathological parameters, including age, menopausal status, tumor size, nuclear grade, re-excision, and adjuvant radiotherapy were analyzed. Follow-up data were obtained from the German cancer registry. The association between re-excision and local recurrence was analyzed using log-rank testing, and multivariate Cox regression was performed to identify independent risk factors. RESULTS:A total of 425 patients were treated for DCIS between 2003 and 2015, with follow-up data available for 247 patients (mean follow-up: 4.4 years). Re-excision was performed in 119 patients (48.2%). Local recurrence occurred in 8 patients (6.7%) with re-excision and in 9 patients (7.1%) without. The 5-year local recurrence rate was 2.9% with re-excision versus 6.0% without (P = .33). Multivariate analysis identified younger age (P = .03) and premenopausal status (P = .02) as significant risk factors, while adjuvant radiotherapy showed a protective effect (P = .01). CONCLUSION:Re-excision was not associated with a significantly different risk of local recurrence. Younger age and premenopausal status were associated with increased recurrence risk, whereas adjuvant radiotherapy was associated with improved local control.

Die Langzeittherapie mit Opioiden ist ein wichtiger Bestandteil der Behandlung chronischer Schmerzen. Sie kann jedoch neben bekannten Nebenwirkungen auch erhebliche endokrinologische Folgen verursachen. Eine der wichtigsten Komplikationen ist der Opioid-induzierte Hypogonadismus (OiH), der durch eine Störung der Hypothalamus-Hypophysen-Gonaden-Achse (HHG-Achse) entsteht. Trotz der hohen klinischen Relevanz wird der OiH häufig nicht erkannt. Gründe hierfür sind unspezifische Symptome sowie ein mangelndes Bewusstsein bei Behandelnden. Auch eine Leitlinie zur Diagnostik und Therapie des OiH existiert bislang nicht. Empfohlen werden aktuell eine Aufklärung der Patientinnen über mögliche Symptome vor Therapiebeginn, die Erhebung eines hormonellen Ausgangsstatus sowie regelmäßige symptomorientierte Kontrollen bei langfristiger Opioideinnahme. Da die hormonellen Veränderungen durch eine Dosisreduktion oder das Absetzen der Opioide reversibel zu sein scheinen, gelten diese therapeutisch als bevorzugte Maßnahme. Ist dies nicht möglich, kann eine Opioidrotation oder in ausgewählten Fällen eine Hormonersatztherapie erwogen werden. Insgesamt sind weitere Studien notwendig, um evidenzbasierte Empfehlungen für Screening und Behandlung des OiH zu entwickeln.

Introduction: Hormone receptor negative breast cancer lacking HER2 overexpression is associated with poor prognosis and limited treatment options. Recent efficacy of anti HER2 antibody drug conjugates in HER2-low (HER2 1+ and HER2 2+/ISH-negative) disease suggests that this subgroup represents a biologically and clinically distinct entity. Analyses of cohorts treated before the availability of HER2 targeted therapies are needed to define the natural disease course and prognostic relevance of HER2 low status. Methods: We retrospectively analyzed data of HR-negative and either HER2-zero or HER2-low breast cancer patients treated in a single clinical center between 2014 and 2024. Primary endpoints included overall survival (OS) and event-free survival (EFS), secondary endpoints included pathological complete response (pCR) after neoadjuvant chemotherapy and clinicopathological characteristics. Results: Among 277 patients, 160 (57.8 %) had HER2-zero, 75 (27.1 %) had HER2 1+ and 42 (15.2 %) HER2 2+/ISH-negative tumors. Higher tumor stages (p = 0.053) and lower Ki-67 indices (p = 0.038) were more prevalent in HER2 2+/ISH-negative patients. OS was significantly worse in HER2 2+/ISH-negative patients (HR 8.12, 95 % CI 1.98–33.37, p = 0.004), whereas EFS and pCR rates did not differ significantly. Patients with pCR after neoadjuvant chemotherapy had significantly better OS (p = 0.007) and EFS (p = 0.003) than those with non-pCR, with no differences among the HER2 subgroups. Conclusion: HER2 2+/ISH-negative status was associated with poorer OS. Distinct clinicopathological features associated with lower pCR rates may have contributed to the inferior survival in this group.

Endometriosis is a common gynecologic disorder often associated with chronic pelvic pain, infertility, and reduced quality of life. Conventional imaging modalities, such as transvaginal ultrasound and MRI, may underestimate the extent of disease, particularly in deep infiltrating endometriosis. Fibroblast activation protein (FAP) is highly expressed in remodeling endometrium and has been implicated in endometriotic lesions. This study investigates the feasibility of integrating FAP-targeted PET/MRI to improve endometriosis detection. Methods: This retrospective study included 18 premenopausal women. The test cohort consisted of 9 patients with suspected or confirmed endometriosis who had undergone FAP-targeted PET/MRI or PET/CT with the FAP inhibitor (FAPI) [68Ga]BED003 (previously known as [68Ga]Ga-OncoFAP-DOTAGA). The reference cohort consisted of 9 premenopausal women without known endometriosis who had undergone FAPI PET/MRI or PET/CT with either [68Ga]BED003 or [68Ga]Ga-FAPI-46 for initial staging of breast cancer. Examinations were not scheduled with regard to the patients' menstrual cycles. Lesions were assessed using a segment-based analysis derived from the #Enzian classification. Focal radiopharmaceutical uptake was semiquantitatively assessed using SUVmax and SUVmean Clinical assessments and laparoscopic findings, when available, served as reference standards. Results: In the test cohort with available PET/MRI data (7 patients and 91 segments), MRI alone identified endometriosis-suspicious findings in 19% of segments. In contrast, combined PET/MRI identified findings in 49% of segments. Among all PET datasets (108 segments per cohort), focal extrauterine FAP uptake was observed in 41% of the test cohort's segments compared with 13% of the reference cohort's segments (P < 0.01). The mean number of PET-positive segments per patient was higher in the test cohort than in the reference cohort (4.9 ± 2.4 vs. 1.7 ± 1.3, P = 0.009), with the greatest difference observed in peritoneal, ovarian, and tubal segments. Uterine SUVmax did not differ significantly between the 2 cohorts (P = 0.489). Where available, PET/MRI findings showed substantial concordance with laparoscopic results. Conclusions: FAPI PET/MRI increased the detection of lesions suggestive of endometriosis compared with MRI alone. These findings support further prospective evaluation of FAPI PET/MRI as an adjunct imaging modality for preoperative assessment of endometriosis.

Endometriosis is a disease associated with pain symptoms and reduced fertility, characterized by the presence of endometrial tissue outside the uterus. SETD3 is an actin-specific histidine N-methyltransferase that regulates actin stability and flexibility. Here, we investigate the effects of altered SETD3 expression on cytoskeletal function and endometriotic cell motility. SETD3 expression in endometriotic lesions was analyzed using EndometDB, and in uteri of the superfertile Dummerstorf mouse line FL1 by RT-qPCR. The functional impact of siRNA-mediated SETD3 depletion on endometriotic 12Z cells and primary endometriotic stroma cells was studied in vitro. Cell motility, contractility, invasiveness, morphology and gene expression were analyzed by RT-qPCR, Western blotting, immunofluorescence, scratch wound, collagen contraction and Matrigel invasion assays. In patient tissue, SETD3 expression was slightly increased in deep endometriotic lesions, whereas SETD3 was downregulated 1.6-fold in the uteri of superfertile mice. SETD3 depletion delayed cell motility, reduced invasiveness of 12Z cells, and reduced the capability to contract collagen gels. Cytoskeletal gene expression was moderately changed. Our data suggest that the histidine N-methyltransferase SETD3 contributes to cytoskeletal remodeling that plays a key role in cell migration and invasion. A dysregulation of SETD3 could therefore be related to the pathogenesis of endometriosis, particularly in deep endometriosis.

Background: Most skin diseases have a hormonal genesis or endocrine trigger factors. Therefore, hormonal contraceptives offer indications for dermatologic treatments. Objectives: The aim of this study was to summarize the effects of oral, vaginal, intrauterine as well as injectable and implantable contraceptives on hormonally adressable dermatoses. Materials and methods: This review was created on the basis of a literature search in Pubmed using the search terms contraception, skin disease, dermatology, hormonal therapy, seborrhea, acne and hirsutism. Results: Combined oral contraceptives and vaginal rings are the most important treatment pillars for the treatment of seborrhea, acne, hirsutism and androgenetic alopecia. Individualized hormonal contraception through the targeted use of gestagen partial effects and advantageous routes of application can minimize unwanted skin rashes. Estrogen-free therapeutics such as hormonal intrauterine devices, the progesterone-only pill or gestagen implants worsen most of the dermatological diseases presented here. Conclusions: Through more intensive research into known contraceptives with objective recording of dermatological (side) effects, further indication areas can be identified in the future.

Adenomyosis, a prevalent gynecologic condition involving invasion of endometrial tissue into the myometrium, remains poorly understood in terms of its molecular pathogenesis. Numb, an important regulator of cellular destiny and stem cell maintenance, has been implicated in numerous proliferative diseases; however, the role for Numb in adenomyosis has not yet been investigated. This research examines the degree to which Numb protein may play a role in the pathogenesis of adenomyosis and additional invasive endometrial diseases. This study analyzed Numb protein expression in tissues from 21 adenomyosis patients and 14 controls using immunohistochemistry. Numb levels were evaluated in eutopic endometrium, ectopic lesions, and myometrium. Additionally, comprehensive bioinformatics analyses were performed including TCGA expression analysis, STRING protein-protein interaction network analysis, and Kaplan-Meier survival analysis to elucidate the clinical significance and mechanistic role of NUMB in endometrial pathology linked to invasive growth. Compared to controls (p < 0.001), adenomyosis patients' eutopic endometrium and myometrium showed considerably higher levels of numb expression. It was predominantly observed in single cells rather than clusters. No significant variation was noted across menstrual cycle phases. Elevated Numb levels in the myometrium suggest a potential role in tissue invasion. TCGA analysis revealed significant associations between NUMB alterations and expression patterns in endometrial carcinoma, with copy number alterations showing a dose-dependent relationship with the expression levels. STRING network analysis identified NUMB as a central hub protein with 20 high-confidence interactions, particularly enriched in Notch signaling pathway components (FDR = 1.0 × 10-15). Kaplan-Meier survival analysis demonstrated that endometrial carcinoma patients with NUMB alterations had significantly better overall survival compared to unaltered cases (p = 9.119 × 10-3), with 92% vs. 73% survival at 100 months. This study presents new evidence of elevated Numb expression in adenomyosis, suggesting that it may play a part in the pathophysiology of the disease and that it is a useful marker for dysregulation of endometrial stem cells. The comprehensive bioinformatics analyses establish NUMB as a central regulator of endometrial homeostasis with significant prognostic value in endometrial malignancies, providing mechanistic insights into the pathogenesis of invasive endometrial diseases and identifying potential therapeutic targets.

Viele Hauterkrankungen haben eine hormonelle Genese oder endokrine Triggerfaktoren. Daher bieten hormonelle Kontrazeptiva interessante dermatologische Einsatzgebiete. Der vorliegende Beitrag fasst anhand hormonell gut adressierbarer Dermatosen erwünschte und unerwünschte Wirkungen oraler, vaginaler, intrauteriner sowie injizier- und implantierbarer Kontrazeptiva zusammen. Diese Arbeit ist auf Basis einer Literaturrecherche in PubMed mit den Suchbegriffen contraception, skin disease, dermatology, hormonal therapy, seborrhea, acne und hirsutism entstanden. In der Behandlung von Seborrhö, Akne, Hirsutismus und androgenetischer Alopezie stellen orale kombinierte Kontrazeptiva und Vaginalringe die wichtigsten Therapiesäulen dar. Eine individualisierte hormonelle Verhütung unter gezielter Nutzung gestagener Partialwirkungen und vorteilhafter Applikationswege kann unerwünschte Hauteffloreszenzen minimieren. Östrogenfreie Therapeutika wie Hormonspirale, „progestogen-only pill“ (POP) oder Gestagenimplantate verschlechtern die meisten hier vorgestellten dermatologischen Erkrankungen. Durch intensivere Erforschung bekannter Kontrazeptiva mit objektivierter Erfassung dermatologischer (Neben‑)Wirkungen lassen sich in Zukunft sicher weitere Indikationsgebiete identifizieren.

Purpose:Endometriosis is a chronic gynecological disorder associated with pain symptoms and infertility. The expression of microRNA miR-29c-3p is dysregulated in endometriosis. We aimed to identify novel molecular targets of miR-29c-3p functionally linked to proliferation and invasive growth in endometriosis. Methods:The epithelial endometriotic cell line 12Z and primary endometriotic stromal cells (PESC) were transfected with control miRNA or pre-miR-29c-3p, and subjected to cell cycle analysis, cell viability, wound healing, and Matrigel invasion assays. Expression of bioinformatically predicted miR-29c-3p targets was analyzed by qPCR and western blot. Target gene expression in endometriotic lesions and healthy endometrium was studied in the EndometDB endometriosis database. Results:miR-29c-3p decreased 12Z and PESC cell viability and the proportion of PESC in the S-phase. 12Z cell invasion, but not migration, was decreased after miR-29c-3p upregulation. miR-29c-3p decreased the mRNA expression of CDK6, BCCIP, TCF7L1, TCF7L2, PTEN, COL4A1, E-Cadherin, and N-Cadherin. A decrease of CDK6 and PTEN and an increase of p21 were confirmed at the protein level. EndometDB database analysis demonstrated dysregulated expression of the selected targets in both deep endometriosis and ovarian endometriosis. Conclusions:miR-29c-3p effectively curbs endometriotic cell proliferation and invasion by combined inhibition of cell cycle regulators and transcription factors, unveiling a promising therapeutic strategy.

INTRODUCTION:Endometriosis is a common gynecological condition, and problems may persist or develop after the menopause. Endometriosis or its treatment in premenopausal women may lead to premature or early menopause. Thus, it is imperative that healthcare providers are appropriately trained in management of endometriosis at the menopause and beyond. AIM:To provide an evidence-based clinical guide for the assessment and management of menopausal health in women with a history of endometriosis. MATERIALS AND METHODS:Review of the literature and consensus of expert opinion. SUMMARY RECOMMENDATIONS:Surgery is the preferred option for managing symptomatic endometriosis after the menopause, as it should reduce pain, ensure an accurate diagnosis, and decrease risk of malignancy. Women with endometriosis may experience a spontaneous early menopause or surgically induced menopause. Endometriosis is also associated with an increased risk of cardiovascular disease, ovarian, breast, and thyroid cancers, as well as osteoporosis. Menopausal hormone therapy (MHT) is indicated for managing vasomotor and genitourinary symptoms and maintaining bone health. Continuous combined MHT may be safer than other forms in both hysterectomized and non-hysterectomized women with endometriosis as the risk of recurrence and malignant transformation of residual endometriosis may be reduced. Estrogen-only MHT should be avoided, even for women who have had a hysterectomy. For women not using MHT, alternative pharmacological treatments, such as neurokinin-3 receptor antagonists, should be considered for managing vasomotor symptoms. Additionally, antiresorptive and anabolic therapies, along with calcium and vitamin D supplementation, should be provided as indicated to ensure skeletal protection. If endometriosis recurs during MHT use and the patient is symptomatic, several management strategies may be employed: altering the regimen, discontinuation, and use of non-hormonal strategies. Herbal preparations should be avoided as their efficacy is uncertain and some may contain estrogenic compounds.

Endometriosis, affecting up to 10% of women in their reproductive years, is a chronic and multifactorial disease characterized by the presence of endometrial tissue outside the uterus. Traditionally associated with pain and infertility, recent studies highlight its systemic nature, implicating inflammatory, immunological, and hormonal dysregulation in its pathogenesis. This paper explores the emerging role of microRNAs (miRNAs) in the pathophysiology of endometriosis and its related infertility. Evidence suggests that dysregulation of specific miRNAs influences cellular proliferation, migration, and progesterone resistance, thereby contributing to the development and progression of endometriotic lesions. Additionally, altered miRNA expression profiles hold promise as non-invasive biomarkers for improving diagnostic accuracy and as potential targets for novel therapeutic interventions. Although current diagnostic methods, such as laparoscopy, remain the gold standard, the integration of miRNA-based approaches could reduce reliance on invasive procedures and enhance treatment outcomes. Ultimately, further research—particularly regarding the interplay between endometriosis and infertility—is crucial to fully elucidate these complex mechanisms and foster the development of more effective diagnostic and therapeutic strategies.

Endometriose ist eine chronisch-entzündliche gynäkologische Erkrankung, deren Prävalenz weltweit bei etwa 10

Endometriosis is a chronic gynecological disorder associated with pain symptoms and infertility. The expression of microRNA miR-29c-3p is dysregulated in endometriosis. We aimed to identify novel molecular targets of miR-29c-3p functionally linked to proliferation and invasive growth in endometriosis. The epithelial endometriotic cell line 12Z and primary endometriotic stromal cells (PESC) were transfected with control miRNA or pre-miR-29c-3p, and subjected to cell cycle analysis, cell viability, wound healing, and Matrigel invasion assays. Expression of bioinformatically predicted miR-29c-3p targets was analyzed by qPCR and western blot. Target gene expression in endometriotic lesions and healthy endometrium was studied in the EndometDB endometriosis database. miR-29c-3p decreased 12Z and PESC cell viability and the proportion of PESC in the S-phase. 12Z cell invasion, but not migration, was decreased after miR-29c-3p upregulation. miR-29c-3p decreased the mRNA expression of CDK6 , BCCIP , TCF7L1 , TCF7L2 , PTEN , COL4A1 , E-Cadherin , and N-Cadherin . A decrease of CDK6 and PTEN and an increase of p21 were confirmed at the protein level. EndometDB database analysis demonstrated dysregulated expression of the selected targets in both deep endometriosis and ovarian endometriosis. miR-29c-3p effectively curbs endometriotic cell proliferation and invasion by combined inhibition of cell cycle regulators and transcription factors, unveiling a promising therapeutic strategy.

The 19th World Congress on Menopause, hosted by the International Menopause Society in 2024, convened global experts to discuss the latest advances in menopause management. This review highlights key focus areas presented at the congress, offering insights into best practices for clinical application. Cardiovascular health remains a priority, with emphasis on recognizing sex-specific risk factors and exploring emerging therapies. Osteoporosis management underscores the role of menopausal hormone therapy (MHT) as foundational, complemented by anti-resorptive and bone-forming agents in high-risk populations and those not candidates for MHT. Addressing genitourinary symptoms and sexual health, vaginal estrogen therapy is confirmed as a safe and effective option with vaginal dehydroepiandrosterone (DHEA) and oral ospemifene as suitable alternatives, while testosterone therapy offers benefits for hypoactive sexual desire disorder in postmenopausal women. Sleep disturbances, depression and workplace challenges linked to menopause were explored, with tailored interventions such as MHT and cognitive behavioral therapy specifically for sleep recommended. Cancer risk management stressed the need for a multidisciplinary approach to risk reduction beginning with lifestyle modification, and with non-hormonal therapies prioritized for symptomatic treatment of menopausal symptoms in those with hormone-sensitive cancers. Lastly, perimenopause management highlighted comprehensive approaches integrating symptom relief and contraceptive needs.

INTRODUCTION:Adenomyosis is a special subtype of endometriosis, affecting the myometrium, affecting about 20% of women in the reproductive age period. Clinical symptoms and intensity are diverse and can vary from heavy menstrual bleeding and dysmenorrhea to infertility and repeated pregnancy losses. Thus, patients often present with a long history of illness pending presumptive clinical or surgical diagnosis. A definitive diagnosis of adenomyosis is made upon histopathological examination verifying ectopic endometrial tissue (endometrial glands and/or stroma) within the myometrium, surrounded by hyperplastic and hypertrophic smooth muscles. However, nowadays ultrasonographic and/or MRI signs can precisely detect it as well. The precise etiology and pathogenesis remain unclear. One theory assumes that adenomyosis occurs through metaplastic transformation or migration of stem cell-like cells. MATERIAL AND METHODS:Our study examined the immunohistochemical expression of the transmembrane proteoglycan Syndecan-1 (CD 138), a multifunctional matrix receptor and signaling co-receptor, in the endometrium of 35 patients (n = 21 with adenomyosis and n = 14 as a control group) in the period 2016-2017. RESULTS:As a pilot study, we concluded that Syndecan-1 is downregulated in adenomyosis patients compared to the control group, supporting its potential role in the development of adenomyosis. Our study did not find a correlation between the immune-expression of Syndecan-1 and the menstrual cycle phase. CONCLUSIONS:For clinical significance in relation to our results, the investigated data showed that the downregulation of Syndecan-1 in adenomyotic patients in our study may suggest a role in promoting the invasiveness of endometriotic islands within the myometrium. However, further studies are still needed to understand the mechanistic contribution of Syndecan-1 to the pathogenesis of adenomyosis.