Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures.
Abstract
Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes—bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances—demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform.
Overall, pesticide exposure is a significant factor in the development and progression of women’s cancers, although the strength of the evidence varies across pesticide classes.
M.Hossein Mirasheh, Zahra Shahabinia, A. Mazidimoradi et al.· Diseases· 0 citations
Overall, evidence linking BPA exposure to ovarian-cancer-related outcomes remains limited, and current findings do not establish that BPA causes OC or worsens patient prognosis in humans.
Lu-Lu Zhang, Tong Yu, Zhong-Liu Bian et al.· Frontiers in Cell and Develo...· 0 citations
Infertility is a growing worldwide health issue that cannot be addressed only by hereditary or behavioural causes. Growing research suggests that endocrine-disrupting chemicals (EDCs), which are pervasive environmental pollutants, are substantial contributors to poor male and female reproductive health, particularly in fast industrialising nations like India. The objective was to comprehensively map and synthesise current knowledge on the origins, mechanisms, and clinical reproductive consequences of EDC exposure, with an emphasis on the implications for infertility practice and public health policy. A scoping review was conducted using the PRISMA-ScR framework. The PubMed/MEDLINE, Scopus, and Web of Science databases were searched for systematic reviews, meta-analyses, umbrella reviews, and significant human and animal research published between January 2014 and June 2025. The Endocrine Society, World Health Organisation, and United Nations Environment Programme provided authoritative position statements. Evidence was synthesised thematically based on exposure sources, molecular pathways, and clinical consequences. EDCs, which include bisphenols, phthalates, pesticides, PFAS, and heavy metals, have been linked to poor sperm quality, testosterone shortage, ovulatory dysfunction, decreased ovarian reserve, endometriosis, poor pregnancy outcomes, and possible transgenerational impacts. Disruption of the hypothalamic-pituitary-gonadal axis, interference with hormone receptors, poor steroidogenesis, oxidative stress, mitochondrial dysfunction, and epigenetic alteration were among the mechanisms implicated. Exposure reduction treatments showed short-term reversibility of biomarker load, indicating therapeutic significance. EDCs are controllable yet underappreciated risk factors for infertility. Integrating exposure assessment, preventative counselling, biomonitoring, and regulatory tightening, particularly in India, may improve reproductive outcomes and supplement assisted reproductive technology.
Vinoth Gnana Chellaiyan Devanbu, J. John, Vijayalakshmi Sridharan· International Journal of Rep...· 0 citations
Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic–pituitary–gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods.
Codruța Claudia Gherman Lencu, Cezara-Andreea Gerdanovics, O. Orășan et al.· International Journal of Mol...· 0 citations
Microplastics (MPs) and nanoplastics (NPs) have emerged as pervasive environmental contaminants with increasing evidence of human exposure and biological accumulation. Recent studies have confirmed their presence in multiple human reproductive tissues and fluids, including semen, testicular tissue, ovarian follicular fluid, cervicovaginal secretions, placenta, and breast milk, raising concerns regarding their potential implications for reproductive health. Beyond their widespread distribution, MPs have been shown in experimental studies to interact with cellular and molecular processes, including oxidative stress, inflammatory responses, mitochondrial dysfunction, and DNA damage, which are pathways commonly implicated in carcinogenesis. This review provides a comprehensive and critical synthesis of current evidence linking microplastic exposure to reproductive cancers, including prostate, testicular, ovarian, endometrial, cervical, and vaginal malignancies. Available mechanistic studies suggest that MPs may influence cancer-related biological processes through dysregulation of programmed cell death, genotoxicity, endocrine disruption, and modulation of signaling pathways such as PI3K/AKT and MAPK. Experimental findings also indicate that MPs may alter the tumor microenvironment and affect cellular behaviors associated with proliferation, migration, and invasion. However, the majority of current evidence is derived from in vitro studies, animal models, and indirect mechanistic observations, while direct epidemiological evidence in humans remain limited. Furthermore, methodological heterogeneity in microplastic detection and characterization complicates comparisons across studies and hinders causal inference. Overall, current evidence supports the biological plausibility of an association between microplastic exposure and reproductive cancer-related processes, while highlighting the need for standardized methodologies and well-designed longitudinal human studies to clarify potential health risks.
B. Rais, A. Vafa, Faten F. Bin Dayel et al.· Journal of Xenobiotics· 0 citations
Major depressive disorder (MDD) accounts for a substantial share of global disability-adjusted life years and remains inadequately treated despite pharmacological advances. Growing evidence implicates endocrine-disrupting chemicals (EDCs)—particularly phthalates and bisphenols—as environmental contributors to the onset of these conditions. This narrative review examines evidence from PubMed, Scopus, and Web of Science (January 2000–March 2025) on the relationship between early-life exposure to these compounds and the development of mood disorders, with emphasis on molecular and neurobiological mechanisms. Phthalates such as di(2-ethylhexyl) phthalate (DEHP), and bisphenols such as bisphenol A (BPA), are detected ubiquitously in human urine, blood, placenta, and umbilical cord blood. Key mechanisms identified include Nrf2/HO-1-driven oxidative stress and neuronal apoptosis, disruption of calcium signalling and synaptic plasticity via CREB phosphorylation deficits, epigenetic suppression of brain-derived neurotrophic factor (BDNF) via promoter hypermethylation, NF-κB/NLRP3/IL-1β neuroinflammatory cascades, interference with thyroid hormone bioavailability through transthyretin competition, and PPAR-mediated disruption of brain lipid metabolism. Prenatal and early-life exposure has been associated with ADHD, cognitive impairment, autism spectrum disorder, and elevated risk of depressive and anxiety phenotypes in epidemiological cohorts. Psychological vulnerability factors—perceived stress, deficient emotion regulation, and adverse childhood experiences—likely amplify this biological susceptibility through HPA axis sensitisation. Methodological limitations of current evidence, including reliance on single-spot urine samples and residual confounding, are critically appraised. Future research priorities include longitudinal biomonitoring cohorts, brain organoid mechanistic models, and integration of validated psychiatric assessments into environmental health study designs.
M. Lastretti, Andrea Faa, Monica Piras et al.· Environments· 0 citations
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