Objective The aim of the German-language S3 guideline on lichen sclerosus (LS) is to provide an evidence- and consensus-based foundation for the diagnosis and management of this disease. The present publication offers a concise summary of the relevant content, focusing on genital LS in girls and women. This first part addresses, among other aspects, the definition, symptomatology, and diagnosis of LS, as well as its management during pregnancy. The separately published second part focuses on the treatment of LS. Methods The German-language, evidence- and consensus-based S3 guideline on LS was developed under the leadership of the German Society of Gynecology and Obstetrics (DGGG) and the German Dermatological Society (DDG), based on the European "EuroGuiDerm Guideline on Lichen Sclerosus." The interdisciplinary guideline panel included 24 experts from 16 professional societies and actively involved patient representatives in the development process. Recommendations LS is a chronic inflammatory skin disease with predominant manifestation in the anogenital region. It may be associated with pruritus, pain, sexual dysfunction, urinary symptoms, and constipation, although it can occasionally remain asymptomatic. Awareness of the broad spectrum of symptoms, as well as reversible and irreversible clinical signs, is essential to enable early diagnosis and appropriate treatment. Early and adequate therapy can not only alleviate symptoms but also reduce the risk of permanent damage and the development of associated carcinomas. During pregnancy, treatment with topical glucocorticoids should be continued as needed to control disease activity and prevent complications.

Objective: To evaluate the real-world effectiveness and tolerability of Iron Hydroxide Adipate Tartrate (IHAT[TM]) in women with iron deficiency across three common obstetric and gynecologic clinical settings: pregnancy, the postpartum period, and abnormal uterine bleeding. Methods: This prospective multicenter observational real-world study included women with iron deficiency managed in routine clinical practice across Italy. Participating gynecologists collected data using standardized case report forms. Patients received IHAT[TM] according to routine clinical practice and were followed for approximately three months. Baseline demographic and hematologic parameters were recorded, including hemoglobin and ferritin levels. The primary outcome was the change in hemoglobin between baseline and follow-up. Secondary outcomes included changes in ferritin levels, treatment adherence, and tolerability. Results: A total of 517 women was included in the analysis. The study population included pregnant women (N = 287, 55.5%), women with abnormal uterine bleeding (N = 161, 31.1%), and women in the postpartum period (N = 69, 13.3%). Improvements in hemoglobin were observed across all clinical settings, with hemoglobin increasing from 10.35 g/dL at baseline to 11.63 g/dL at three months, corresponding to a mean increase of 1.28 g/dL. Mean ferritin levels increased from 22.50 ng/mL to 37.74 ng/mL in three months. Treatment adherence was high or moderate in 93.4% of patients. Gastrointestinal adverse events were infrequent, with constipation (9.7%) and nausea (4.8%) among the most reported. Conclusions: In this prospective real-world multicenter study, treatment with IHAT[TM] was associated with meaningful improvements in hemoglobin and iron stores in women with iron deficiency across pregnancy, postpartum, and abnormal uterine bleeding. The treatment showed good adherence and a favorable tolerability profile in routine clinical practice.

Sunflower pectin is widely used as a food additive due to its gelling and stabilizing properties. However, its bioactive potential remains poorly understood. Here, we explored its effect on defecation. Using a diphenoxylate-induced constipation mouse model, we found that native sunflower pectins did not significantly promote defecation. Subsequently, we investigated whether they could be activated via biotransformation. For this, we enzymatically hydrolyzed the pectin and produced a number of fragments that covered a wide range of molecular weights (0.5 to 30 kDa) in two esterification states (0% and 10% methyl esterification). Interestingly, all fragments exhibited defecation-promoting effects. Moreover, the effect progressively increased as the molecular weight decreased, a trend that was observed with both esterified and non-esterified fragments. Comparative studies identified E3 as the most effective fraction. E3 also displayed a prebiotic effect in the gut of model mice. Structural analysis indicated that E3 comprises oligogalacturonides with degrees of polymerization from one to six, mainly DP3 and DP4. Overall, our study reveals an inverse correlation of molecular weight with defecation-promoting activities, and offers a simple and scalable approach to convert ineffective pectin into effective oligogalacturonides that have the potential to become functional food ingredients.

PACS1 neurodevelopmental disorder (PACS1-NDD) is characterized by mild-to-severe neurodevelopmental delays. Language skills are more severely affected than motor skills. Hypotonia is reported in about a third of individuals and is noted to improve over time. Approximately 60% of individuals are ambulatory. Feeding difficulty is common, with 25% requiring gastrostomy tube to maintain appropriate caloric intake. Other common features include constipation, seizures, behavioral issues, congenital heart anomalies, short stature, and microcephaly. Common facial features include hypertelorism, downslanting palpebral fissures, bulbous nasal tip, low-set and simple ears, smooth philtrum, wide mouth with downturned corners, thin upper vermilion, and wide-spaced teeth. To date approximately 35 individuals with PACS1-NDD have been reported.

Slow transit constipation (STC) involves impaired colonic motility, and effective therapies remain limited. Inulin-type fructans (ITFs) are prebiotic polysaccharides linked to intestinal function, but mixtures with broad chain-length distributions hinder structure-function interpretation. In this study, we adopted a degree of polymerization (DP)-anchored strategy to compare two structurally related ITFs from Asparagus cochinchinensis: ACO (DP = 6) and ACNP (DP = 15). In a loperamide (LOP)-induced STC model, ACNP, but not ACO, improved fecal output and water content, shortened the time to first black stool, and enhanced intestinal transit. ACNP alleviated colonic injury, restored mucus-associated protection, improved epithelial barrier integrity, and preserved enteric neurons and nerve-fiber networks. Multi-omics analyses showed that ACNP treatment was associated with enrichment of Akkermansia muciniphila (AKK), restoration of kynurenic acid (KYNA), reduced proinflammatory mediators, and attenuated NLRP3 inflammasome activation. Antibiotic depletion largely abolished these benefits, whereas fecal microbiota transplantation (FMT) restored them. Moreover, live AKK supplementation and exogenous KYNA reproduced key protective effects and were associated with reduced NLRP3 inflammasome activation. Overall, this DP-anchored comparison identified ACNP as the more effective fructan fraction and supports a microbiota-dependent protective response involving AKK enrichment, KYNA restoration, NLRP3 inflammasome attenuation, barrier protection, and enteric nervous system (ENS) preservation.

Endometriosis is a benign yet chronic gynecologic condition that, in rare cases, may undergo malignant transformation. Although endometriosis-associated malignancies most commonly arise in the ovary, extragonadal sites may also be affected. Endometriosis-associated intestinal tumors (EAITs) are exceptionally rare and often difficult to diagnose. We report the case of a 73-year-old woman with a remote history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with rectal bleeding and constipation. Imaging and colonoscopy revealed a nearly obstructing mass in the sigmoid colon, initially suspected to be primary colorectal carcinoma. Biopsy demonstrated a poorly differentiated carcinoma with squamous features. Immunohistochemical analysis supported a Müllerian origin, an unexpected finding given the patient's prior gynecologic surgery. Sigmoidectomy subsequently revealed a high-grade endometrioid carcinoma with extensive squamous differentiation arising from intestinal endometriosis. This rare case highlights that endometrioid carcinoma can develop from intestinal endometriosis decades after definitive gynecologic surgery. Accurate diagnosis requires the integration of clinical history, histopathological findings, and immunohistochemical results to differentiate this entity from primary colorectal carcinoma. Increased awareness of EAITs is essential to ensure accurate diagnosis and appropriate management.

Uterine leiomyomas are the most common benign tumors in women of reproductive age. Although hysterectomy is the definitive treatment for symptomatic fibroids, uterine-preserving procedures are preferred in young women, particularly when fertility is desired. Hysterectomy in women in their 20s due to extensive leiomyomatosis is uncommon. We report the case of a 25-year-old multiparous woman who presented with progressive abdominal distension, constipation, heavy menstrual bleeding, and dysmenorrhea for one year. Examination revealed a large abdominopelvic mass extending to the xiphisternum. Imaging demonstrated a massive, multinodular uterine mass that replaced the uterus. Following counseling regarding myomectomy and possible hysterectomy, an exploratory laparotomy was performed. Intraoperatively, the uterus was completely replaced by multiple leiomyomata, making myomectomy impossible. Total abdominal hysterectomy with ovarian conservation was undertaken. The specimen measured 22 × 17 × 8 cm and weighed 4.1 kg. Histopathology confirmed multiple benign leiomyomas without atypia or malignant features. Recovery was uneventful. This case highlights that uterine preservation should be pursued whenever safely feasible; however, hysterectomy may represent the safest option when complete replacement of the uterus precludes reconstruction.

Imlunestrant is a next-generation, oral, selective estrogen receptor degrader approved for treating adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated advanced/metastatic breast cancer. Imlunestrant is metabolized partly by cytochrome P450 (CYP)3A4 oxidation and conjugation with glucuronic acid and sulfate; thus, pharmacokinetic and drug-drug interaction (DDI) studies for treatments utilizing similar pathways are essential for clinical development. Three open-label, phase 1 studies enrolled 182 healthy females of nonchildbearing potential to assess the tolerability, safety, and pharmacokinetics of imlunestrant as monotherapy or coadministered with other drugs. Drug concentrations were quantified by validated liquid chromatography-mass spectrometry. Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Frequent treatment-related adverse events included headache (range, 4%-20%), diarrhea (2%-20%), and constipation (0%-16%). In the presence of imlunestrant, exposures (AUC0-∞) increased for dextromethorphan 1.33-fold (90% CI, 1.22-1.46), digoxin 1.39-fold (1.22-1.59), and rosuvastatin 1.49-fold (1.14-1.97). Imlunestrant exposure (AUC0-∞) decreased in combination with quinidine (CYP2D6 inhibitor) 0.87-fold (90% CI, 0.76-1.00) and carbamazepine (CYP3A4 inducer) 0.58-fold (0.49-0.69), but increased in combination with itraconazole (CYP3A4 inhibitor) 2.11-fold (1.77-2.53). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities.