What's new in endo & adenomyosis research

(No abstract on file for this paper.)

Corrected R1 release accompanying the revised manuscript submitted to the International Journal of Women's Health (manuscript 643362). This archive contains analysis code, cached inputs, derived result tables, reproducibility instructions and file checksums. The revision corrects variant-identity matching and duplicate handling, recalculates multiple-testing and power analyses, updates complete-window colocalization, and reanalyzes GSE7305 using paired samples. The corrected screen includes 9,157 unique gene–cell-type tests and prioritizes 10 genes across 28 MR/colocalization pairs. These findings support exploratory genetic prioritization and do not establish therapeutic efficacy. The README documents the reproducible analyses, archived ancillary results and remaining limitations.This record provides the corrected R1 analysis code and derived results for manuscript 643362. It supersedes the analysis files in the earlier deposit (https://doi.org/10.5281/zenodo.21234009) for the revised manuscript.

Some women with adenomyosis respond poorly to progestins, and conventional grey-scale ultrasound cannot reliably identify them before treatment. This thesis reviews studies published in 2022–2025 on ultrasound elastography of adenomyotic lesions. Lesion stiffness is higher than that of normal myometrium, is accompanied by higher expression of fibrosis markers and correlates with the severity of dysmenorrhoea. In women treated with dienogest for six months, higher lesion stiffness was associated with symptom relapse after treatment was stopped. No study has yet reported a stiffness threshold that predicts insufficient response during treatment. Elastography therefore deserves evaluation as a component of prognostic models of response to progestin therapy.

Background: Abnormal uterine bleeding (AUB) is a frequent gynecological disorder affecting women of reproductive age and beyond. It presents as irregular, heavy, or prolonged bleeding, negatively impacting the quality of life for a significant proportion of women globally. The FIGO PALM-COEIN classification facilitates the distinction between structural and non-structural etiologies of AUB, supporting evidence-based management strategies. Objective: To analyze the pharmacological treatments, causative factors, risk profile, and management approaches for AUB in women attending the Obstetrics and Gynecology Department at MIMS Tertiary Care Hospital, Mandya. Methodology: This prospective crosssectional observational study enrolled 172 women aged 18—50 years who presented with AUB. Patient demographic information, menstrual history, comorbidities, structural findings (via USG and PALM-COEIN classification), diagnostic modalities, and treatment regimens were systematically recorded and analyzed utilizing descriptive statistics and a structured patient profile format. Results: Women aged 39—50 years comprised the majority of cases (51%), with irregular heavy bleeding being reported by 76.2%, frequently accompanied by pelvic pain and dysmenorrhea (55.2%). Thyroid disorders were the predominant comorbidity (87%), followed by PCOS (7%) and diabetes (3%). Structural etiologies determined using PALM-COEIN classification revealed leiomyoma as the leading cause (54.7%), with polyp (19.8%), adenomyosis (15.1%), and endometriosis (10.5%) also commonly seen. Most cases (64%) were managed surgically, while 36% received medical treatment. Meprate (48.4%) and Regesterone (33.9%) were the preferred oral hormonal agents, both representing progestin therapy. Paracetamol was the most commonly prescribed analgesic (51.9%), and Tranexamic acid (53%) was slightly favored over Mefenamic acid (47%) for antifibrinolytic intervention. Postoperative support centered on iron and vitamin supplementation, with Metronidazole and Ceftriaxone as the primary antibiotic regimen. Conclusion: AUB most often affects middleaged women, manifesting with irregular heavy bleeding and thyroid gland dysfunction as the most frequent comorbidity. Leiomyoma remains the principal structural cause. Surgical management predominates, while rational, individualized medical therapy supports comprehensive, patient-centered care. Early diagnosis and tailored treatment improve outcomes in AUB

La endometriosis es una enfermedad inflamatoria crónica, estrógeno-dependiente y heterogénea, asociada con dolor pélvico, infertilidad y deterioro significativo de la calidad de vida. Durante los últimos años, su abordaje ha experimentado una transformación sustancial, particularmente por el abandono progresivo de la laparoscopia como requisito universal para establecer el diagnóstico, el mayor protagonismo de la evaluación clínica y de las técnicas de imagen especializadas, y la incorporación de nuevas alternativas farmacológicas. El objetivo de esta revisión fue analizar críticamente la evidencia contemporánea sobre el diagnóstico y tratamiento de la endometriosis, integrando estrategias farmacológicas, quirúrgicas y reproductivas, así como los avances dirigidos hacia una atención individualizada. Se realizó una revisión narrativa estructurada de literatura científica y guías clínicas, priorizando publicaciones entre 2020 y 2026. El manejo actual debe orientarse por los síntomas, fenotipo y localización de la enfermedad, edad, deseo reproductivo, reserva ovárica, tratamientos previos y preferencias de la paciente. Las terapias hormonales continúan siendo fundamentales para el control del dolor, mientras que los antagonistas de la hormona liberadora de gonadotropinas amplían las opciones en casos refractarios. La cirugía mantiene indicaciones específicas y requiere una valoración individualizada, especialmente ante endometriomas, endometriosis profunda e infertilidad. La evidencia actual favorece un modelo longitudinal, multidisciplinario y centrado en la paciente.

Диеногест широко применяется для консервативного лечения аденомиоза, однако часть пациенток не получает достаточного облегчения боли или прекращает приём из-за маточных кровотечений. Цель обзора — обобщить опубликованные в 2021–2026 гг. данные о клинических, эхографических и эластографических показателях, которые позволяют выделить таких пациенток до начала лечения. Поиск выполнен в базах PubMed и Europe PMC, в обзор включено 19 публикаций. По данным метаанализов, диеногест снижает дисменорею в среднем на 5,86 см по визуальной аналоговой шкале, но результаты исследований очень неоднородны. С худшим результатом связаны старший возраст, высокий уровень CA-125, объём матки более 352,7 см³, диффузная форма аденомиоза, сопутствующая миома и кровотечения на фоне терапии; размеры матки лучше всего предсказывают кровотечения. Ультразвуковые признаки MUSA связаны с тяжестью симптомов, но как предикторы ответа на диеногест не изучались. Жёсткость очага по данным эластографии отражает выраженность фиброза, коррелирует с тяжестью дисменореи и ассоциирована с рецидивом после отмены препарата. Прогностическая модель, объединяющая три группы показателей, пока не создана и требует проспективной проверки.

В тезисе рассмотрены исследования 2021–2025 гг. о клинических и ультразвуковых признаках, позволяющих до начала лечения заподозрить недостаточный эффект диеногеста у пациенток с аденомиозом. Худший долгосрочный результат связан со старшим возрастом и высоким уровнем CA-125, а объём матки более 352,7 см³ указывает на повышенный риск неудачи терапии. Диффузная форма аденомиоза и сопутствующая миома ассоциированы с более слабым ответом. Длинник матки и толщина миометрия по данным трансвагинального исследования предсказывают кровотечения, из-за которых препарат чаще всего отменяют. Признаки MUSA связаны с тяжестью симптомов, но как предикторы ответа на диеногест не изучались. Предложен минимальный набор показателей для оценки перед назначением препарата.

Background: Endometriosis causes pelvic pain and fatigue, impairing physical fitness and sports participation. While physical activity helps manage symptoms, precise exercise programming guidance remains limited. Aim: This narrative review evaluates sports science and clinical evidence relevant to individualized exercise programming for women with endometriosis. Material and methods: PubMed was the principal database, supplemented by Google Scholar and Scopus. The search covered publications from 2016–2026, including systematic reviews, meta-analyses, interventional studies, and guidelines. Evidence was classified as direct, component (multimodal), or extrapolated. Results: A favourable signal arises from progressive multimodal physical activity programmes, though evidence certainty is low and active components cannot be isolated. Yoga and assessment-guided pelvic floor training have direct, population-specific support. No validated endometriosis-specific FITT (Frequency, Intensity, Time, Type) training protocol is established. Modality selection should reflect dominant symptoms, pelvic floor findings, and responses to physical loading. Conclusions: Targeted physical activity is a valuable management component, but a universal training prescription is currently unjustified. A symptom-responsive framework is offered to guide exercise professionals; comparative dose-finding sports science trials are required before firm recommendations can be made.

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

We report a case of a 55-year-old female who presented to the emergency department with symptoms of appendicitis.Imaging demonstrated appendiceal mucocele and possible early appendicitis.She underwent a laparoscopic appendectomy and subsequent histopathology demonstrated irregular fibrosis of the appendiceal wall as a result of endosalpingiosis with secondary mucocele formation.In this report, we present an exceedingly rare case of endosalpingiosis causing an appendicitis mimic.Although endosalpingiosis is typically considered a benign incidental finding, appendiceal involvement can mimic acute appendicitis, as in this case, and may be associated with an increased risk of gynecologic malignancy.The patient was followed up with the gynecological team due to this malignancy risk and is planned for laparoscopic oophorectomy, with the final histopathology diagnosis being appendiceal endosalpingiosis with secondary mucocele.

Pelvic pain may persist despite guideline-concordant endometriosis care. Evidence for primary motor cortex repetitive transcranial magnetic stimulation (M1-rTMS) in this population is limited. We assessed daily pain and activity interference, treatment delivery and safety after clinically indicated M1-rTMS. A prospective, single-centre observational cohort enrolled women with confirmed endometriosis and chronic pelvic pain. Ten left M1-rTMS sessions were scheduled over two weeks (10 Hz, 80% resting motor threshold, 1500 pulses/session). Daily diaries recorded pelvic pain and activity interference during pre-treatment, treatment, and post-treatment days 1–28 and week 8. Changes were estimated using linear mixed-effects models. Forty-two participants were enrolled and 40 initiated treatment; analyses included 37 for pain and 35 for interference. Model-based marginal mean pain decreased from 5.69 to 4.69 (change, −1.00; 95% CI, −1.46 to −0.55; p < 0.001), and interference from 6.03 to 4.63 (change, −1.39; 95% CI, −1.84 to −0.95; p < 0.001). Both remained below pre-treatment at week 8. Ten of 34 evaluable participants achieved ≥30% pain reduction and three achieved ≥50%. Of the 400 planned sessions, 386 were delivered; a total of 33/40 participants attended all ten and 38/40 at least eight. Twenty-eight participants reported 47 treatment-emergent adverse events; one was severe, none was serious, and all were resolved. M1-rTMS was feasible to deliver with high protocol fidelity and acceptable tolerability. Modest reductions in pain and activity interference were observed, although clinically important pain relief occurred in a minority; without a sham, usual-care, or untreated comparator, these changes cannot be attributed causally to rTMS. Controlled trials are required to determine efficacy and optimal dosing.

Ectopic adrenal cortical tissue (EACT) is an uncommon developmental heterotopia and is exceptionally rare in the ovary of adult women. A 52-year-old woman, 6 years after menopause, was evaluated for progressive enlargement of a uterine leiomyoma and postmenopausal spotting. Transvaginal ultrasonography and pelvic magnetic resonance imaging demonstrated multiple uterine leiomyomas but no adnexal mass or endometrioma. During total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, dense adhesions between the sigmoid colon and posterior cul-de-sac were unexpectedly encountered. Histopathologic examination of the adhesion-related tissue revealed neither endometriosis nor significant inflammatory change. Microscopic examination of the ovary identified a 1.9 mm, sharply circumscribed nodule composed of clear, vacuolated zona fasciculata-like cells and compact eosinophilic zona reticularis-like cells. The lesional cells showed diffuse Melan-A immunoreactivity and focal-to-patchy inhibin-α positivity, supporting adrenocortical differentiation. The findings established a diagnosis of ovarian EACT. This case emphasizes that microscopic ovarian adrenal rests may be radiologically occult and should be distinguished from ovarian steroidogenic neoplasms by integrating clinical, morphologic, and immunohistochemical findings.

Endometriosis and adenomyosis are characterized by the presence of endometrial-like tissue outside its normal anatomical location and are associated with pain, infertility, and other clinical manifestations. Although they share pathogenic features, including inflammation, hormonal responses, immune dysregulation, and fibrosis, their clinical and histopathological phenotypes are highly heterogeneous. This review integrates tissue mechanics and mechanobiology with inflammation, hormonal signaling, oxidative stress, angiogenesis, and neurogenesis to propose a microenvironment-dependent framework for understanding lesion formation, maintenance, and progression. Direct measurements of tissue stiffness, including elastography, have been reported, but standardized comparisons among lesion types remain limited. Existing evidence suggests that tissue stiffening may affect cellular proliferation, invasion, fibrosis, and tissue remodeling through mechanotransduction pathways such as integrin signaling. However, much of this evidence derives from in vitro studies, experimental models, or other fibrotic diseases, and direct causal relationships in human endometriosis and adenomyosis remain insufficiently established. Conversely, chronic inflammation, recurrent bleeding, and ECM accumulation may contribute to both tissue stiffening and fibrosis, indicating reciprocal interactions between mechanical and biological processes. Thus, lesion phenotypes may reflect interactions among lesion origin, cell-intrinsic properties, and the local microenvironment. Mechanobiology may complement established inflammatory, hormonal, immune, and fibrotic concepts and provide hypotheses for understanding lesion heterogeneity and progression. Longitudinal, lesion-level studies integrating mechanical and biological parameters are needed to test these hypotheses.

Ovarian fibromas are uncommon benign sex cord-stromal tumors that frequently present as unilateral solid masses and may mimic ovarian malignancy, particularly in postmenopausal women.Preoperative diagnosis remains challenging because imaging findings and tumor markers often overlap with those of other adnexal lesions.We present the case of an ovarian fibroma initially misdiagnosed as an endometrioma, illustrating the limitations of preoperative assessment.We report the case of a 60-year-old postmenopausal woman with an incidentally detected right adnexal mass initially interpreted as an endometrioma on transvaginal ultrasound and computed tomography (CT).The patient subsequently underwent laparoscopic resection, and histopathological examination confirmed the diagnosis of ovarian fibroma.Ovarian fibromas may mimic other adnexal masses, making preoperative diagnosis challenging.Imaging studies and serum tumor markers have limited specificity and may be insufficient to reliably distinguish these tumors from other ovarian lesions.In postmenopausal women, persistent solid adnexal masses generally warrant surgical exploration regardless of ancillary findings.Therefore, definitive diagnosis of ovarian fibroma relies on histopathological examination.Ovarian fibroma remains an important differential diagnosis of solid adnexal masses in postmenopausal women.The limitations of preoperative assessment reinforce the role of surgical excision, while histopathological examination remains the gold standard for definitive diagnosis.

Endosalpingiosis (ES) is a benign, nonneoplastic condition of the Müllerian system characterized by the ectopic implantation of fallopian tube-like ciliated columnar epithelium. Unlike endometriosis, ES lacks endometrial stroma and therefore does not produce the characteristic hemorrhagic episodes or extensive inflammatory responses associated with endometriosis. Although ES is primarily identified in the visceral pelvic peritoneum, extrapelvic manifestations are exceedingly rare, with pulmonary and pleural localization, accounting for ∼0.1% of reports. This report describes the clinical presentation of thoracic ES in a 40-year-old woman who presented with catamenial spontaneous primary pneumothorax. Despite a remote surgical history for ovarian endometriosis 10 years earlier, the patient had a prolonged period of clinical latency and no evidence of current pelvic recurrence. Videothoracoscopic surgery revealed a 5-mm apical pulmonary nodule and diffusely calcified pleural plaques. Histopathology and immunohistochemistry are remain gold-standard diagnostic methods for differentiating ES from thoracic endometriosis syndrome or malignancy. The diagnosis was confirmed by epithelial immunoreactivity for Müllerian transcription factors (PAX8 and WT1), keratin 7, and estrogen/progesterone receptors, together with the absence of cluster of differentiation 10 expression, which argued against endometrial stroma, and calretinin negativity, which argued against mesothelial origin. The pathophysiology of thoracic ES may resemble that of pulmonary endometriosis, involving transdiaphragmatic or vascular migration of Müllerian cells. For symptomatic presentations, surgical excision combined with long-term suppressive hormonal therapy is recommended to reduce epithelial proliferation. Given that the emerging literature suggests a possible link between ES and gynecological malignancies, rigorous long-term postoperative surveillance remains essential.

(No abstract on file for this paper.)

Secondary analysis of the NIH All of Us Research Program examining how polyendocrine metabolic ovarian syndrome (PMOS, formerly polycystic ovary syndrome) and endometriosis are recorded across participant surveys and electronic health records, and whether agreement between the two sources varies with access to care. Protocol and preregistration by Akshaya Sahasra Ganji and Aamuktha Yalamanchili (The Unknown Now).

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

Chanchan Ma,1– 3 Shibo Huang,4 Lihuan Song,5 Ying Luo,6 Honglan Zhu1,31Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Obstetrics and Gynecology, North China Medical Health Group Fengfeng General Hospital, Handan, Hebei, People’s Republic of China; 3Obstetrics and Gynecology Teaching and Research Office, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 5Independent Researcher, Fuzhou, Fujian, People’s Republic of China; 6Department of Pathology, Fujian Maternal and Child Health Hospital, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Honglan Zhu, Email [email protected]: Endometriosis (EM) and polycystic ovary syndrome (PCOS) are two prevalent endocrine-related gynecological conditions with shared pathophysiological pathways, yet their population-level burden patterns and socioeconomic correlates across Europe remain unclear. This study examines the geographic overlap in population-level disease burden patterns of EM and PCOS (hereafter referred to as ecological co-distribution), which does not represent individual-level comorbidity.Methods: Using the Global Burden of Disease (GBD) 2023 dataset, we retrieved incident cases and disability-adjusted life years (DALYs) data for EM and PCOS among women aged 15– 49 years covering 44 European countries (1990– 2023). Countries were classified into three population-level burden phenotypes (consistent pattern, EM-predominant pattern, PCOS-predominant pattern) by cross-tabulating quartiles of age-standardized incidence rates (ASIR). Temporal trajectories were quantified via the estimated annual percentage change (EAPC) method combined with Joinpoint regression modeling. Additional analyses included age-stratified burden distribution, correlation with the Socio-demographic Index (SDI), and decomposition analysis of burden drivers.Results: EM and PCOS exhibited diametrically opposite spatial gradients: EM burden concentrated in Central and Eastern Europe, while PCOS burden predominated in Western Europe. Only 7 countries showed consistent dual-disease burden levels, with 19 EM-dominant and 18 PCOS-dominant countries. From 1990 to 2023, ASIR of both diseases declined across most subregions. The age-standardized DALY rate (ASDR) of EM declined in Western Europe but showed a non-monotonic trajectory in Eastern Europe, whereas PCOS ASDR increased substantially across all regions. EM incidence was weakly but significantly negatively correlated with SDI, whereas both incidence and disability burden of PCOS showed significant positive associations with SDI. Decomposition analysis indicated that epidemiological shifts drove rising PCOS disability, while demographic changes mainly contributed to EM burden reduction.Conclusion: EM and PCOS exhibit geographically divergent burden patterns with differing socioeconomic gradients across Europe, underscoring the need for regionally differentiated reproductive health strategies.Keywords: Endometriosis, Polycystic ovary syndrome, GBD 2023, Geographic disparity, SDI

Objective: to investigate changes in uterine artery blood flow across stages I–II of adenomyosis. Material and methods : a prospective cohort study was conducted in 45 women of reproductive age. The main group consisted of 31 patients with adenomyosis (18 with stage I, 13 with stage II). The control group included 14 healthy women without gynecological or other medical condition. All participants underwent spectral Doppler examination of the uterine arteries with assessment of the pulsatility index (PI), resistance index (RI), and systolic-diastolic ratio. Statistical analysis was performed using the Mann-Whitney U test. Results : the study demonstrated pronounced stage-dependent variability of uterine artery blood flow parameters in adenomyosis. In stage I adenomyosis, a significant decrease in vascular resistance compared to the control group was observed (RI 0.77±0.003 vs 0.91±0.005; p<0.001), which may reflect enhanced local vascularization and reduced arteriolar tone. In stage II adenomyosis, a phenomenon of “pseudonormalization” of hemodynamic parameters was identified (PI 2.97±0.003), which could be indirectly related to subsequent structural remodeling of the myometrium, including possible fibrotic changes and vascular compression. Conclusions: the hemodynamic profile of uterine arteries in adenomyosis is dynamic and changes with disease progression: from hypervascularization and decreased vascular resistance in early stages to a relative increase in vascular resistance.

(No abstract on file for this paper.)

Ovarian endometrioma is associated with infertility, whereas its treatment may compromise ovarian reserve. This retrospective cohort evaluated factors associated with spontaneous pregnancy after laparoscopic treatment of ovarian endometrioma, with particular attention to the Endometriosis Fertility Index (EFI) and reproductive outcomes after cystectomy using the stripping technique vs ethanol sclerotherapy. Forty-eight infertile women with histologically confirmed ovarian endometrioma and revised American Society for Reproductive Medicine stage III-IV endometriosis underwent laparoscopic treatment between 2022 and 2024 in Kinshasa, Democratic Republic of the Congo, with follow-up through June 2026; 33 underwent cystectomy, and 15 underwent ethanol sclerotherapy. Overall, 29/48 women (60.4%) had primary infertility, 30/48 (62.5%) had bilateral endometriomas, and 29/48 (60.4%) had stage IV disease. Spontaneous pregnancy occurred in 17/48 women (35.4%), and 11/48 (22.9%) achieved a live birth. Pregnancy occurred in 9/15 women (60.0%) after sclerotherapy vs 8/33 (24.2%) after cystectomy (p = 0.024). Among women with EFI ≥7, 15/26 (57.7%) conceived, compared with 2/22 (9.1%) with EFI <7 (p < 0.001). In the adjusted Cox model, EFI ≥7 (adjusted hazard ratio (aHR) 7.96, 95% confidence interval (CI) 1.78-35.57; p = 0.007) and ethanol sclerotherapy (aHR 3.11, 95% CI 1.17-8.29; p = 0.023) were associated with a higher rate of spontaneous pregnancy. Both ovarian-reserve markers improved in 15/15 women (100.0%) after sclerotherapy vs 9/33 (27.3%) after cystectomy (p < 0.001). These findings suggest that a favorable EFI identifies women with a higher likelihood of spontaneous pregnancy and that ethanol sclerotherapy may offer reproductive advantages over cystectomy; however, the retrospective design, small sample, and nonrandomized treatment allocation limit causal inference.

Purpose: We aim to synthesize recent clinical and translational evidence on the relationship between endometriosis and ovarian cancer, with emphasis on publications from 2024 to 2026 and on clinically conservative risk stratification. Materials and methods: This state-of-the-art narrative review prioritizes major peer-reviewed publications from July 2024 to June 2026. Older landmark publications were used only where necessary to contextualize recent findings. Results: Recent evidence supports a selective, phenotype-dependent association instead of a generalized malignant potential of endometriosis. The strongest and most reproducible signal concerns epithelial ovarian cancer, especially clear-cell and endometrioid ovarian carcinoma, with the highest relative risks reported for ovarian endometrioma and/or deep endometriosis. The ENDOCANCER meta-analysis found increased ovarian cancer risk across odds ratio, hazard ratio and standardized incidence ratio estimates but confirmed low absolute incidence and substantial heterogeneity. Contemporary reviews, including Leone Roberti Maggiore et al. and Bogani et al., emphasize low absolute lifetime risk and the absence of evidence supporting universal oncologic surveillance. Newer clinicopathological studies distinguish endometriosis-correlated tumors supported by transitional lesions indicative of malignant transformation from incidental coexistence. Molecular data support biological plausibility through ARID1A, PIK3CA, KRAS, PTEN, mismatch repair deficiency, POLE-mutated disease and p53-abnormal phenotypes, but these markers are not ready for routine prediction in endometriosis care. Conclusions: The immediate clinical implication is individualized risk assessment in place of routine cancer screening or prophylactic surgery based solely on the increased cancer risk associated with endometriosis. Counseling should integrate endometriosis phenotype, age, menopausal status, lesion dynamics, imaging atypia, hereditary cancer risk, reproductive goals and surgical consequences.

Endometriosis is a chronic, systemic, inflammatory disease characterized by the presence of endometrium-like tissue growing outside of the uterus. Affecting one in ten individuals assigned female at birth, it causes chronic pain and inflammation that significantly impairs quality of life. Yet the mechanisms that drive pain and disease progression remain poorly defined. This study establishes the precise spatial transcriptomic cartography of human ovarian and peritoneal lesions, two of the most commonly found lesions. We identify shared spatial features across lesion types, including immune cell infiltration, fibroblast compartments surrounding epithelial glands, and distinct distributions of neuronal and macrophage subsets. We precisely defined sensory neuronal subtypes and mapped their spatial location relative to immune cells. We further validate the epithelial-neuronal interactome, using an in vitro 3D model of peripheral sensory brain organoids co-cultured with human endometriosis epithelial and fibroblast cells. By mapping spatial cellular interactions and conserved features across lesion types linked to pain, our study advances understanding of endometriosis pathophysiology and informs targeted therapeutic development. Haney et al. map human endometriosis lesions and reveal shared cellular organization across endometriosis lesion types, identifying fibroblast compartments, neuro-immune interactions, and painsensing neurons, modeled in 3D co-culture systems.

A endometriose é uma doença ginecológica crônica, inflamatória e estrogênio-dependente, marcada pela presença de tecido semelhante ao endométrio fora da cavidade uterina, com repercussões importantes sobre dor, fertilidade e qualidade de vida. Sua fisiopatologia é multifatorial e envolve alterações hormonais, imunológicas, genéticas, epigenéticas, inflamatórias e metabólicas, além da interação com o microbioma e mecanismos relacionados ao estresse oxidativo e à fibrose. Nesse contexto, a heterogeneidade clínica e molecular da doença contribui para atrasos diagnósticos e limitações terapêuticas, uma vez que as abordagens disponíveis frequentemente controlam os sintomas, mas não eliminam a doença nem impedem sua recorrência.

(No abstract on file for this paper.)

(No abstract on file for this paper.)

This study aimed to investigate temporal changes in epithelial–mesenchymal transition (EMT), hormone receptor balance, and inflammatory markers at the tissue protein level following dienogest (DNG) treatment in a mouse model of adenomyosis, and to propose preliminary hypotheses regarding the temporal differences in the expression of these proteins. A mouse model of adenomyosis was established using tamoxifen. Following successful model establishment, the model and control groups received peanut oil by gavage, whereas the 2-, 4-, and 6-week DNG intervention groups received DNG at 0.303 mg/kg/day by gavage for 2, 4, and 6 weeks, respectively. At the end of each treatment period, the expression of E-cadherin, N-cadherin, ER, PR, IL-6, IL-1β, vimentin, NGF, and VEGF in uterine tissues was assessed by immunohistochemistry, followed by statistical analysis using the appropriate methods. Compared with the control group, the expression of N-cadherin, IL-1β, NGF, ER, Vimentin, IL-6, and VEGF in the uterine tissues of mice in the model group increased (P<0.05), E-cadherin decreased (P0.05). Compared with the model group, after 2 weeks of intervention with dienogest, the protein levels of NGF, Vimentin and VEGF were down-regulated (P<0.05), and the protein levels of PR and IL-6 were increased (P<0.05). After 4 weeks of intervention with dienogest, the expression levels of N-cadherin, NGF, ER, and E-cadherin were decreased (P<0.05). When the intervention was extended to 6 weeks, IL-6 expression level increased (P0.05). Short-term (2-4 weeks) DNG intervention appears to modulate EMT, exhibit a regulatory trend on hormone receptors, and temporarily alleviate the local inflammatory microenvironment. However, long-term (6 weeks) intervention suggests a potential attenuation of these observed effects, which may be related to the combined effects of multiple tissue-level changes, including altered progesterone receptor responsiveness, inflammatory microenvironment disorders, and the pathological progression of EMT. However, direct evidence for receptor desensitization or other specific mechanisms is currently lacking. This study merely observed changes in protein expression at the tissue level, further research is needed to elucidate the underlying mechanisms.

Ovarian endometrioid carcinoma (OEC) is a major histotype of endometriosis-associated ovarian carcinoma, yet the spatial distribution of cancer-associated mutations and the clonal relatedness of synchronous endometrial and ovarian carcinomas (SEOC) remain incompletely understood. In this study, we performed spatially controlled molecular profiling of OEC using laser capture microdissection, droplet digital PCR, targeted amplicon sequencing, and exploratory whole-exome sequencing. We analyzed multiple tumor regions and selected stromal compartments from OEC and SEOC cases to assess the intratumor distribution of hotspot mutations in CTNNB1, PIK3CA, and KRAS and to evaluate molecular relatedness between ovarian and endometrial lesions in SEOC. Cancer-associated mutation signals showed spatially heterogeneous distributions in a subset of histologically uniform OEC. In SEOC, shared alterations supported clonal relatedness in selected cases. Low-level hotspot mutation signals were also detected in microdissected stromal compartments immediately adjacent to tumor glands, although their cellular origin remains to be determined. These findings suggest that single-region molecular testing may underestimate spatial molecular heterogeneity in OEC and provide a framework for understanding the clonal relatedness of endometriosis-associated gynecologic carcinomas.

Oxidative stress (OS) has been proposed to play a role in the development of endometriosis (EMs). Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. Our previous study has shown that ROS generation is obviously increased in ectopic endometrial stromal cells with inhibition of PRXD4 expression. In our present study, IHC results indicate that the PRDX4 expression was increased in the ectopic endometria of ovarian EMs. Moreover, overexpression of PRDX4 effectively promotes cell migration. In addition, compared with vector group, overexpression of PRDX4 significantly reduces oxidative stress damage induced by H2O2, including increased cell viability, decreased intracellular H2O2 content, and reduced apoptosis rate. Interestingly, we found that the antioxidation effect of PRDX4 disappeared when the active cysteine residues (Cys124 and Cys245) were replaced with serine. To gain further insight into the antioxidant mechanism of PRDX4, our results shown that overexpression of PRDX4 decreased PTP1B oxidation and phosphorylation cascades. The in vivo findings showed that PRDX4 promoted the growth of ectopic lesions. Taken together, our results indicate that PRDX4 functions as a suppressor in injuries caused by oxidative stress, suggesting that inhibiting PRDX4 expression could be an effective treatment strategy for EMs.

“Endometriosis and Secondary Musculoskeletal Pain: A Scoping Review” explores the musculoskeletal manifestations that may occur secondary to chronic pain and inflammation associated with endometriosis. Persistent pelvic pain may contribute to pelvic floor overactivity, myofascial pain, low-back and hip pain, altered movement patterns, and lumbopelvic dysfunction, leading to functional limitations and reduced quality of life. This scoping review aims to map the existing evidence on secondary musculoskeletal pain in women with endometriosis, including its characteristics, possible mechanisms, associated factors, assessment methods, functional impact, and rehabilitation approaches. It will also identify gaps in current evidence and highlight the need for comprehensive multidisciplinary and physiotherapy-based management.

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

The female reproductive tract microbiome is associated with reproductive outcomes, but its composition and clinical meaning vary by anatomical site, hormonal state and sampling method. Evidence was assessed across vaginal community structure, low-biomass endometrial sampling, infertility, endometriosis and pregnancy complications. Lactobacillus-associated functions, including lactic-acid production and host interaction, provide plausible mechanisms, while community-level and strain-level variation complicate simple classifications of health and dysbiosis. Assisted reproduction and pregnancy studies identify associations that require careful adjustment for treatment, gestational timing and host characteristics. Experimental work on Fusobacterium and microbial metabolites offers mechanistic hypotheses for endometriosis, but does not establish routine antimicrobial treatment. Trials of selected lactobacilli demonstrate that microbiome-directed interventions can alter vaginal outcomes; their findings cannot automatically be extended to fertility or live birth. Functional measurements, contamination control and prospectively validated clinical endpoints are essential before microbiome profiles can reliably guide reproductive care.

Background: Adenomyosis is a common benign gynecological condition associated with dysmenorrhea, heavy menstrual bleeding, and chronic pelvic pain. Symptoms may become more troublesome during the perimenopause. This study aimed to evaluate the effectiveness of hormonal treatment in perimenopausal women with adenomyosis. Methods: This hospital-based observational study was conducted in the Department of Obstetrics and Gynecology, Netrokona Medical College and Hospital, Netrokona, Bangladesh, over a period of one year, from January 2025 to December 2025. The study included 100 premenopausal women diagnosed with adenomyosis who visited the Obstetrics and Gynecology department during the study period. Results: Dienogest was the most commonly used treatment (35.0%), followed by combined oral contraceptives (25.0%) and the levonorgestrel-releasing intrauterine system (22.0%). The mean VAS pain score decreased significantly from 6.1 ± 1.8 at baseline to 3.2 ± 1.6 at 6 months (p<0.001). Heavy menstrual bleeding decreased from 44.0% to 12.0%, while dysmenorrhea decreased from 82.0% to 38.0% after treatment. Overall, 78.0% of participants showed clinical improvement. The highest improvement rate was observed with dienogest (85.7%), although the difference between treatment groups was not statistically significant (p=0.083). Irregular vaginal bleeding or spotting was the most common adverse effect (27.0%), while 48.0% of participants reported no adverse effects. Conclusion: Hormonal treatment was effective in reducing pain and menstrual bleeding and improving clinical symptoms among perimenopausal women with adenomyosis. These findings suggest that hormonal therapy may provide an effective conservative option for symptom control and uterine preservation

Endometriosis is a chronic, oestrogen-dependent inflammatory disease affecting an estimated 10% of women of reproductive age. The mean diagnostic delay is 6–7 years.Current evidence supports viewing endometriosis beyond a purely gynaecological condition: it combines peripheral inflammation, central sensitisation, genetic susceptibility and associations with other chronic conditions.Objective. To provide a structured protocol integrating the contributions of the gynaecological (endometriosis) surgeon, reproductive medicine specialist, radiologist, pain specialist, colorectal surgeon, urologist, psychologist, pelvic-floor physiotherapist, dietitian and other team members.Methods. The protocol synthesises the ESHRE 2022 guideline, NICE NG73, ACOG guidance, the IDEA ultrasound and WES classification consensus statements, Cochrane reviews and key randomised trials (Section 4). Primary sources and GRADE-based guidelines were prioritised.Results. A six-step patient pathway is proposed: (1) clinical suspicion and early recognition; (2) non-invasive imaging; (3) empirical therapy and a personalised plan; (4) surgery in a centre of expertise where indicated; (5) recovery, rehabilitation and long-term suppression; (6) outcome monitoring (PROMs) and comorbidity screening.Conclusions. Managing endometriosis as a chronic, multisystem condition through a coordinated team may improve pain control, quality of life and reproductive outcomes. The protocol requires local adaptation and independent expert verification before clinical use

To evaluate whether the intensity of pain symptoms in women with adenomyosis and endometriosis is associated with the specific lesion localizations or with disease extension. A retrospective investigation was performed on 234 women with sonographic diagnosis of adenomyosis and endometriosis (cases), of whom 174 (74.4%) had adenomyosis, 89 (38.0%) superficial endometriosis, 103 (44.0%) ovarian endometriosis, and 131 (56.0%) deep infiltrating endometriosis (DIE) of the utero-sacral ligaments (USL; n = 76), rectum ( n = 61), parametrium ( n = 46), and vesical-uterine folder ( n = 13); 75 control women were also enrolled. Menstrual and intermenstrual pain, deep dyspareunia, dysuria, dyschezia, and low back pain were rated on a visual analogue scale (VAS). The modification of each symptom with therapy was evaluated in the 123 women receiving progestin-only (P; n = 81) or estro-progestin (EP; n = 42) treatment, also comparing P versus EP. Concomitant lesions were more frequent (78.6%) than single localizations (21.4%). Superficial endometriosis was independently associated with more intense menstrual pain (median difference 2.62, 95% CI 1.10–4.15), deep dyspareunia (median difference 1.91, 95%CI 0.09–3.74), and low back pain (median difference 2.03, 95%CI 0.06–3.99), and with higher odds of dyschezia (OR 2.44, 95%CI 1.01–5.89). Ovarian endometriosis was associated with more intense menstrual pain (median difference1.93, 95%CI 0.63–3.24) but with less intense intermenstrual pain (median difference − 2.30, 95%CI -3.89 to -0.71) and deep dyspareunia (median difference − 3.17, 95%CI -4.97 to -1.38). DIE of the USL was associated with lower odds of dyschezia (OR 0.36, 95%CI 0.14–0.92), whereas adenomyosis and DIE of the rectum or parametrium were not independently associated with any pain symptom. The response to therapy did not differ among localizations for most symptoms: women with ovarian endometriosis had higher odds of a smaller-than-average reduction of intermenstrual pain (OR 3.04, 95%CI 1.12–8.26), and women with DIE of the parametrium of deep dyspareunia (OR 5.31, 95%CI 1.02–27.60). A poorer response of deep dyspareunia was observed in women receiving P than EP (OR 4.03, 95%CI 1.49–10.92). At baseline all symptoms were more intense in cases than in controls except dysuria; at follow-up they remained higher except for menstrual pain and dysuria. The intensity of pain and its response to hormonal therapy were associated with the specific lesion localizations, rather than with the number of concomitant lesions. Superficial endometriosis appears to be the localization associated with more intense pain symptoms.

Endometriosis Profunda en Ginecología: Diagnóstico, Evaluación y Abordaje Terapéutico es una obra especializada que aborda de manera integral el diagnóstico y manejo de la endometriosis profunda, considerando sus manifestaciones clínicas, evaluación diagnóstica y alternativas terapéuticas. Su enfoque busca facilitar la toma de decisiones en ginecología y contribuir a una atención individualizada de las pacientes.

This review compares perioperative and selected postoperative outcomes between robotic-assisted surgery and conventional laparoscopy in females undergoing surgical treatment for colorectal or rectosigmoid endometriosis.This systematic review and meta-analysis followed the PRISMA 2020 guidelines.PubMed, Web of Science, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and African Journals Online (AJOL) were searched from January 2020 to August 2026 for comparative observational studies evaluating robotic-assisted versus conventional laparoscopic surgery specifically for colorectal or rectosigmoid endometriosis.Manual bibliographic searches of the reference lists of relevant articles were also conducted to identify additional eligible studies.Studies involving general, superficial, ovarian, or deep endometriosis without separately identifiable colorectal disease were excluded.Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers, with disagreements resolved by discussion.Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), and random-effects meta-analysis was undertaken only for outcomes with sufficiently comparable and non-duplicated data.Eight comparative observational reports met the eligibility criteria.Across studies reporting operative duration, robotic-assisted surgery was generally associated with longer operative time than conventional laparoscopy, although the magnitude and statistical significance of this difference varied between cohorts.Estimated blood loss, overall postoperative complications, conversion to open surgery, and most other perioperative outcomes were broadly comparable between approaches.Length of hospital stay showed inconsistent findings across studies, while selected reports suggested possible differences in voiding dysfunction, reoperation, recurrence, postoperative opioid use, and other longer-term outcomes.Considerable clinical and methodological heterogeneity was present because of differences in colorectal lesion complexity, extent of bowel surgery, associated pelvic procedures, institutional experience, follow-up duration, and outcome definitions.Potential overlap between several reports from the same specialist centre was addressed at the outcome level to avoid duplicate contribution of participants to pooled estimates.Overall, robotic-assisted surgery appears to be a feasible alternative to conventional laparoscopy for colorectal endometriosis, but current evidence does not demonstrate a consistent perioperative superiority of either approach.Because all available evidence is observational and susceptible to selection bias, residual confounding, temporal effects, and cohort overlap, causal conclusions cannot be drawn.Further prospective, multicentre, independently recruited comparative studies with standardized perioperative and long-term outcome reporting are required.

Introduction Adenomyosis is a uterine disorder defined by presence of endometrial glands and stroma within the myometrium with surrounding myometrial hyperplasia. Research has shown that ultrasound (US) can play a key role in early adenomyosis diagnosis and treatment. The Morphological Uterus Sonographic Assessment (MUSA) recently published standardized criteria for ultrasonographic diagnosis of adenomyosis, but the relationship between these criteria and clinical symptoms, has yet to be clinically validated. Objectives To assess the prevalence of MUSA ultrasound criteria of adenomyosis and relationship between rates of ultrasound features and clinical symptoms of adenomyosis. Methods This is an analytical cross-sectional study of patients aged 18–52 receiving a transvaginal ultrasound for any indication at a single outpatient imaging center. Patients were excluded if they had a hysterectomy and/or bilateral oophorectomy, were in menopause, or had active gynecologic malignancy. Patients completed a survey to assess for infertility or fertility-related healthcare use, heavy menstrual bleeding, and pelvic pain. Ultrasound images were assessed by a radiologist using MUSA criteria to evaluate for adenomyosis. Multivariate analyses assessed association between MUSA features and patient-reported symptoms. Results Of 271 recruited participants, 11.4% had at least one direct feature of adenomyosis, 57.6% had no direct features but at least one indirect feature, and 31.0% had no features. After controlling for potential confounders in multivariable analysis, patients with direct features resulted in 5.955-point higher heavy bleeding scores compared to those with no features (95% CI 1.970-9.939, p=0.004). When controlling for covariates, the association between indirect features and adenomyosis symptoms were not significant. Subjects with middle myometrium invasion reported increased rates of infertility (p=0.006), whereas subjects with outer myometrial involvement reported significantly higher heavy bleeding (p=0.002). Conclusions Per MUSA criteria, 1 in 10 participants displayed ultrasonographic findings strongly suggestive of presence of adenomyosis. Patients with direct features were more likely to experience heavy menstrual bleeding. Layer of uterine involvement were found to have greater association with infertility and pelvic pain than any one MUSA feature.

Endometriosis and ovarian cancer share invasive, inflammatory, and pro-survival mechanisms in which CXCR4 signaling may play an important role, yet phytochemical modulators of this receptor remain insufficiently characterized. This study addressed that gap by integrating receptor reconstruction, ligand-guided docking, pharmacokinetic and toxicity prediction, pharmacophore mapping, density functional theory, replicated membrane-embedded molecular dynamics, and MM/GBSA analysis. A native human CXCR4 model was generated using SWISS-MODEL with 98.2% template coverage and 100% sequence identity, while the co-crystallized IT1t ligand defined the docking cavity. Eighteen phytochemicals were screened, and naringenin achieved the most favorable predicted docking score (-6.361 kcal/mol), exceeding apigenin (-5.927 kcal/mol) and IT1t (-5.155 kcal/mol). Naringenin formed predicted interactions with Tyr116, Arg188, and Tyr255, showed acceptable drug-likeness, solubility, and gastrointestinal absorption, and displayed a wider HOMO-LUMO gap than apigenin. Two independent 100 ns simulations of the CXCR4 complexes with naringenin, apigenin, and IT1t indicated comparatively consistent structural behavior for naringenin, supported by RMSD, SASA, radius of gyration, hydrogen-bond, PCA, FEL, and DCCM analyses. MM/GBSA estimates were also more favorable for naringenin than apigenin across both replicas. Its predicted LD50 was 2000 mg/kg (toxicity class 4), emphasizing that favorable receptor interactions do not establish safety and require experimental toxicological assessment during further preclinical development. Collectively, naringenin emerged as the most coherent in silico prioritized CXCR4-binding candidate. However, the absence of receptor-binding assays, functional validation, and in vivo confirmation remains a major limitation.

To compare the 12-month clinical outcomes of laparoscopic RFA alone with those of laparoscopic RFA combined with LNG-IUS in patients with symptomatic adenomyosis. This single-center retrospective cohort study included 70 patients with adenomyosis who had complete 12-month follow-up data. Based on the treatment documented in their medical records, patients were classified into an RFA-alone group (group A, n = 35) and an RFA-plus-LNG-IUS group (group B, n = 35). The primary outcome was the change in VAS score from baseline to 12 months. Continuous outcomes were analyzed using two-way mixed-design repeated-measures analysis of variance, with particular attention to the group-by-time interaction. Significant group-by-time interactions were observed for VAS score, menstrual volume, and uterine volume at 12 months. Compared with RFA alone, RFA plus LNG-IUS was associated with greater reductions in VAS score (difference in change, − 0.60 points; 95% CI, − 1.06 to − 0.14; P = .012), menstrual volume (− 25.00 mL; 95% CI, − 35.11 to − 14.89; Holm-adjusted P < .001), and uterine volume (− 14.00 cm³; 95% CI, − 17.10 to − 10.90; Holm-adjusted P < .001). At 1 month, the combined-treatment group showed a greater increase in hemoglobin (difference in change, 14.00 g/L; 95% CI, 11.51 to 16.49; Holm-adjusted P < .001) and a greater reduction in CA125 (− 7.10 U/mL; 95% CI, − 11.09 to − 3.11; Holm-adjusted P = .003). No significant group-by-time interactions were observed for white blood cell count, red blood cell count, or platelet count. In this retrospective cohort, adding LNG-IUS to laparoscopic RFA was associated with greater 12-month improvements in pain, menstrual volume, and uterine volume than laparoscopic RFA alone. These preliminary findings require confirmation in larger prospective studies with longer follow-up.

The aim of this study is to develop a new drug for the prevention and treatment of endometriosis in women based on the phytoestrogen combination with one of the most widely used progestogens – dydrogesterone. The study was conducted on sexually mature female rats weighing 200–220 g. Endometriosis was experimentally modelled according to the method of M.W. Vernon and E.A. Wilson, with modifications. Females with a regular 4–5-day oestrous cycle were selected for the surgical modelling of endometriosis. All operations were performed during the oestrus phase, standardising the conditions for the transplantation of uterine fragments at the same stage of the oestrous cycle. Following the induction of acute endometriosis, which developed 30 days after the operation, the rats were divided into three groups of six animals each. Group 1 (the control group with endometriosis) received distilled water orally once daily for 21 days; Group 2 – endometriosis + medication (Investigate sum 5 + dydrogesterone 10 mg/kg); Group 3: endometriosis + a drug comparable to that used in clinical practice – Lindinet 20 mg/kg administered orally once daily for 21 days. Following the final administration of the test drug, the rats were euthanised by instantaneous decapitation under light ether anaesthesia. Following necropsy, a visual assessment was carried out to evaluate the formation of endometrioid heterotopias at the implantation sites. The implanted tissues were measured in two planes, excised from the surrounding tissues and fixed in neutral 10% formalin for subsequent histological examination. The experiments revealed that, under the influence of the drug and Lindinet 20, the volume of endometriotic implants decreased significantly by a factor of 1.8 and 1.4, respectively, compared with the control group. The volume of endometriotic implants in the control group increased 1.2-fold after 30 days compared with the initial value.

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)

(No abstract on file for this paper.)