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Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women

ABSTRACT: This study aims to elucidate the effect of stress, measured by different approaches, in the endometrial function in In Vitro Fertilization treatments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE310309 | GEO | 2026/02/16

REPOSITORIES: GEO

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Project description:Background: The endometrium, regulated by steroid hormones, is particularly susceptible to disease under imbalanced hormonal conditions. Progesterone regulates cell growth differently across tissues, acting as a pro-tumorigenic agent in the breast while serving as a tumor suppressor in the endometrium by countering the effects of oestradiol. Progesterone receptor modulators like mifepristone may prevent breast cancer formation but raise concerns about unopposed oestradiol exposure in the endometrium. This study examines mifepristone’s impact on the endometrium, particularly its potential link to endometrial carcinogenesis in BRCA mutation carriers, who have DNA repair and replication vulnerabilities. Methods: This study was part of a randomised, double-blind, placebo-controlled trial in which pre-menopausal women carrying BRCA1 or BRCA2 mutations were assigned to a three-month treatment with either mifepristone (50 mg) or a non-hormonal comparator (TrioB) every second day. Endometrial biopsies were collected pre- and post- treatment, processed, and analysed for changes in endometrial thickness, cellular composition, methylation patterns, and gene expression profiles. Compliance and safety monitoring were rigorously maintained. Results: Mifepristone treatment led to amenorrhea in all treated participants, consistent with its inhibition of ovulation. Ultrasound showed a non-significant increase in endometrial thickness post-treatment. Cellular analysis indicated a shift in composition, with a reduction in epithelial cells and an increase in fibroblast levels, suggesting that endometrial thickening may primarily reflect stromal expansion rather than epithelial proliferation. This distinction is clinically important, as epithelial proliferation is more closely associated with carcinogenesis. DNA methylation analysis revealed no significant alterations in the TCGA-EC methylation index, and gene expression profiling showed no significant elevation in carcinogenesis-related genes. Conclusions: Mifepristone treatment in BRCA mutation carriers does not significantly impact methylation or gene expression profiles associated with endometrial carcinogenesis. The findings support from the safety of short-term mifepristone use in this population, although long-time safety of mifepristone use in BRCA mutation carriers will be needed.

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Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women

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