Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin‐releasing hormone analogue (GnRH‐a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low‐grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early‐staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone‐sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small‐sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS‐associated endometrial cancer (LS‐EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS‐EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS‐EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR‐immunohistochemistry (MMR‐IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo‐oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS‐EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability‐high (MSI‐H)/mismatch repair‐deficient (dMMR) EC.

The female reproductive tract microenvironment includes microorganisms, metabolites, and immune components, and the balance of the interactions among them plays an important role in maintaining female reproductive tract homeostasis and health. When any one of the reproductive tract microorganisms, metabolites, or immunity is out of balance, it will affect the other two, leading to the occurrence and development of diseases and the appearance of corresponding symptoms and signs, such as infertility, miscarriage, premature delivery, and gynecological tumors caused by infectious diseases of the reproductive tract. Nutrients in the female reproductive tract provide symbiotic and pathogenic microorganisms with a source of nutrients for their own reproduction and utilization. At the same time, this interaction with the host forms a variety of metabolites. Changes in metabolites in the host reproductive tract are related not only to the interaction between the host and microbiota under dysbiosis but also to changes in host immunity or the environment, all of which will participate in the pathogenesis of diseases and lead to disease-related phenotypes. Microorganisms and their metabolites can also interact with host immunity, activate host immunity, and change the host immune status and are closely related to persistent genital pathogen infections, aggravation of infectious diseases, severe pregnancy outcomes, and even gynecological cancers. Therefore, studying the interaction between microorganisms, metabolites, and immunity in the reproductive tract cannot only reveal the pathogenic mechanisms that lead to inflammation of the reproductive tract, adverse pregnancy outcomes and tumorigenesis but also provide a basis for further research on the diagnosis and treatment of targets.

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Uterine leiomyosarcoma (uLMS) is a rare but malignant gynaecological tumour with a poor survival outcome. The present study was aimed at identifying the key genes and pathways in the development of uLMS through bioinformatics analysis. To minimize the frequency of false-positive results of the bioinformatics analysis, 3 microarrays including GSE764, GSE64763 and GSE68312 were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened out using the online tool GEO2R. Then, Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. Finally, a protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape, and module analysis was conducted using the plug-in MCODE. A total of 95 DEGs including 21 upregulated genes and 74 downregulated genes were identified. The upregulated DEGs were annotated with 'DNA metabolic process', 'nucleobase-containing compound biosynthetic process' and 'cellular macromolecule biosynthetic process', while the downregulated DEGs were annotated with 'cellular response to chemical stimulus', 'movement of cell or subcellular component' and 'response to inorganic substances'. The results of the PPI network analysis demonstrated that matrix metallopeptidase 9, apolipoprotein E, cyclin E1 and syndecan 1 were the predominant upregulated genes in uLMS. Additionally, the genes in the main module were enriched in 'proteoglycans in cancer', 'p53 signalling pathway' and 'extracellular matrix-receptor interaction'. The key genes and pathways identified in the present study may provide valuable clues for clarifying the molecular mechanism underlying the development of uLMS and demonstrate promise for use as diagnostic markers and therapeutic targets.