Background: Endocrine-disrupting chemicals (EDCs) are synthetic and natural compounds that interfere with hormonal regulation and are linked to obesity, diabetes, thyroid disorders, reproductive dysfunction, and hormone-sensitive cancers. Despite European regulatory measures, human exposure persists through food, consumer products, and the environment, raising significant public health concerns.
Objectives: This systematic review and meta-analysis aimed to estimate the prevalence of EDC exposure in European populations and evaluate associations with major endocrine-related health outcomes.
Methodology: A comprehensive search of PubMed, EMBASE, Web of Science, and Scopus identified observational studies published between January 2000 and July 2025. Eligible studies reported biomonitoring data on key EDCs (bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), dioxins, and organochlorine pesticides) and/or statistically assessed associations with endocrine outcomes. Data extraction and risk-of-bias assessment were conducted independently by two reviewers using the Newcastle-Ottawa Scale. Random-effects meta-analysis generated pooled prevalence estimates and effect sizes, with subgroup analyses by region, sex, age, and chemical class. Heterogeneity was quantified using I², and publication bias was assessed via funnel plots and Egger’s test.
Results: Preliminary findings indicate widespread detection of PFAS and phthalates, particularly in Western and Northern Europe, with growing evidence of links to metabolic and reproductive outcomes.
Conclusion: EDC exposure remains a significant and under-recognised public health issue in Europe. This review highlights the need for strengthened regulatory frameworks, ongoing surveillance, and further research to mitigate the long-term health risks associated with EDCs.

Endocrine-disrupting chemicals, Environmental exposure, Bisphenol A, Phthalates, Thyroid, reproductive health, Diabetes, Obesity.

Endocrine-disrupting chemicals (EDCs) are exogenous compounds capable of interfering with the normal functioning of hormonal systems. These chemicals include industrial solvents, plasticizers, pesticides, flame retardants, and pharmaceutical agents that persist in the environment and accumulate in human and animal tissues.[1,2] Human exposure occurs through multiple routes: dietary intake, dermal contact, inhalation, and maternal-fetal transfer. The most studied EDCs include BPA, phthalates, PFAS, polychlorinated biphenyls (PCBs), and dioxins.[3,4]

In Europe, EDC exposure is a significant public health issue due to widespread industrialization and chemical use in consumer goods. Despite the European Union’s proactive regulatory stance embodied in policies such as Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), many EDCs remain in circulation and are detectable in human biological samples across the continent.[5,6]

Problem statement:
The burden of endocrine-related disorders such as obesity, diabetes mellitus, thyroid dysfunction, infertility, and hormone-dependent cancers has been rising steadily across European populations. Concurrently, there is accumulating evidence linking these health outcomes to EDC exposure. However, current data are fragmented, often limited to specific regions, populations, or chemicals. A comprehensive synthesis of prevalence data and health outcomes is lacking, making it difficult to guide public health policies or set evidence-based regulatory thresholds. There is an urgent need to consolidate evidence across Europe to understand the magnitude and impact of EDC exposure.

Justification of the study:
This review is justified by the growing burden of non-communicable diseases (NCDs) potentially associated with environmental exposures. EDCs have been identified as modifiable risk factors for endocrine and metabolic disorders. By synthesizing prevalence data and associations with health outcomes, this study aims to fill a critical evidence gap that will inform European public health strategies, environmental safety regulations, and targeted research. It aligns European (EU) priorities for sustainable development, disease prevention, and reduction of environmental health risks.[7]

Research questions:

• What is the prevalence of exposure to major EDCs in European populations between 2000 and 2025?
• What are the most common endocrine-related health outcomes associated with EDC exposure in Europe?
• How do exposure levels and health outcomes vary across European regions, age groups, and sexes?
• What is the overall strength of evidence linking EDCs to endocrine and metabolic health effects in Europe?

Research aim:
To assess the prevalence of endocrine-disrupting chemicals and their associations with endocrine-related health outcomes in European populations through a systematic review and meta-analysis.

Research objectives:

• To determine the prevalence of key EDCs (BPA, phthalates, PFAS, etc.) in European populations.
• To identify and synthesize observational evidence linking EDC exposure to endocrine-related health outcomes in Europe.
• To explore geographic, demographic, and chemical-specific variations in EDC exposure and related outcomes.
• To evaluate the quality and consistency of the available evidence using meta-analytic techniques.

Literature review:
Epidemiological evidence of health outcomes: Recent literature has highlighted the complex interplay between environmental factors, metabolic health, and healthcare delivery, particularly in relation to EDCs and their role in shaping public health trends across the world. For instance, the narrative review by Nnonyelu et al.[8] and Mansi et al.[9] emphasize the significance of shared decision-making in obesity management, a condition increasingly linked to EDC exposure, reflecting a growing need for integrative approaches across healthcare systems.[10,11] Similarly, the systematic review by Chinua et al.[12] explores the chemobiological underpinnings of obesity and advances in bariatrics, shedding light on how persistent organic pollutants may dysregulate metabolic pathways.

In addition, innovations in immunosuppressive therapy, as discussed by Chinua et al.[13] indirectly underscore the susceptibility of endocrine and immune systems to environmental toxicants, including EDCs, within vulnerable populations such as transplant recipients. Furthermore, the comparative review by Chinua et al.[14] highlights evolving strategies in bariatric medicine, many of which are necessitated by the growing burden of obesity, potentially exacerbated by endocrine disruptors, as demonstrated in the human early life exposome (HELIX) cohort^, and POEM study.[15,16]

Together, these studies provide critical insights into the multifaceted impact of EDCs on health outcomes, particularly within the European context, where regulatory frameworks and healthcare models continue to evolve in response to rising metabolic and immunological disorders.[17] Numerous epidemiological studies have linked EDC exposure to adverse endocrine-related outcomes. BPA and phthalates have been associated with increased risk of obesity, insulin resistance, and type 2 diabetes.[18,19]

PFAS exposure has been connected to thyroid dysfunction and immune modulation.[20,21] Evidence also suggests that prenatal EDC exposure may result in long-term reproductive dysfunction, altered puberty timing, and reduced fertility.[22,23] However, heterogeneity in study design, population characteristics, and biomarker quantification methods contributes to inconsistencies across findings. The scientific literature surrounding EDCs has grown substantially in recent decades. Numerous studies have investigated their biological mechanisms, population-level exposures, and health effects. Europe has been at the forefront of EDC research and regulation, with significant contributions from academic institutions, government agencies, and environmental health networks.[24,25]

Mechanisms of action of EDCs: EDCs interfere with the endocrine system by mimicking, blocking, or altering hormone production and metabolism. These disruptions can occur via interactions with estrogen, androgen, thyroid, or glucocorticoid receptors, leading to altered cellular signaling, gene expression, and developmental programming. Such mechanisms have been demonstrated in both in-vitro and in-vivo studies, often at low-dose exposures and during critical windows of development such as prenatal and early postnatal periods.[26,27]

Commonly studied EDCs in Europe: Among the most studied EDCs in European contexts are BPA, phthalates, PFAS, dioxins, and PCBs. BPA and phthalates are commonly found in plastics and food packaging, PFAS in non-stick coatings and textiles, and dioxins/PCBs in industrial by-products. Bio-monitoring studies have detected these compounds in blood, urine, breast milk, and adipose tissue samples across European populations.[28]

Exposure sources and pathways: EDC exposure in Europe occurs through multiple sources, including contaminated food and water, inhalation of indoor air, dermal absorption from personal care products, and transplacental transfer during pregnancy.[25,26] Dietary intake remains the predominant pathway, particularly through consumption of processed foods and animal fats. Regional variation in exposure is also influenced by socioeconomic status, urban versus rural living, and national chemical regulations.[27]

Regulatory and research responses in Europe: The European Union has led global efforts in chemical safety through legislation such as REACH and the Chemicals Strategy for Sustainability. These frameworks aim to reduce human exposure to harmful substances, including EDCs, by improving chemical assessment, risk management, and transparency.[29] In parallel, initiatives like the Human Biomonitoring for Europe (HBM4EU) project have generated harmonized exposure data across member states, advancing research and policy-making.[28]

Gaps in the literature: Despite a substantial body of evidence, major gaps persist in understanding the cumulative effects of EDC mixtures, low-dose chronic exposures, and vulnerable population impacts. Moreover, limited meta-analytic work has been conducted to quantify pooled associations across Europe. This underscores the need for a comprehensive synthesis of available evidence to support data-driven decision-making.

Study design: This study employed a systematic review and meta-analysis design to synthesize evidence from observational studies on the prevalence of EDCs and their associations with endocrine-related health outcomes in European populations. The methodology followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reproducibility.[30]

Eligibility criteria: The eligibility criteria for this review included observational studies, such as cross-sectional, case-control, and cohort designs, conducted among human subjects residing in any European country. Studies were required to provide a quantitative assessment of exposure to one or more EDCs, including BPA, phthalates, per- and polyfluoroalkyl substances (PFAS), and dioxins. Eligible outcomes encompassed endocrine-related health conditions, including obesity, diabetes, thyroid dysfunction, infertility, and hormone-sensitive cancers. Only publications written in English and published between January 1, 2000, and July 1, 2025, were considered.

Data sources and search strategy: A comprehensive literature search was conducted in the following databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus. The search strategy will combine Medical Subject Headings (MeSH) and keywords such as “endocrine disruptors,” “bisphenol A,” “phthalates,” “PFAS,” “thyroid,” “diabetes,” “infertility,” and “Europe.” Boolean operators (AND, OR) were applied to optimize sensitivity and specificity.

Study selection process: All retrieved articles were imported into EndNote for de-duplication. Two independent reviewers screened titles and abstracts for relevance. Full-text articles were then assessed for eligibility using the predefined criteria. Disagreements were resolved through discussion or consultation with a third reviewer.

Data extraction: A standardized data extraction form was used to collect the following information, as shown in Table 1:

Table 1: Standardized form used to collate relevant data

Quality assessment: The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of included studies. This tool evaluates selection, comparability, and outcome/exposure assessment domains. Studies were categorized as low, moderate, or high quality based on NOS scores.

Data synthesis and meta-analysis: A narrative synthesis was provided for all included studies. Where data were sufficiently homogeneous, meta-analyses were performed using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Subgroup analyses explored variations by chemical type, geographic region, age group, and sex.

Risk of bias and publication bias: Risk of bias across studies was evaluated using the NOS. Publication bias was assessed through funnel plot visualization and Egger’s test, where ≥10 studies are available.

Dissemination plan: The results of this systematic review and meta-analysis were submitted for publication in a peer-reviewed environmental health or public health journal and presented at relevant international conferences on environmental epidemiology and endocrine research.

Overview of study selection: We identified 774 records from databases and registers through an initial search of PubMed, EMBASE, Web of Science, and Scopus, focusing on the research questions and objectives. After removal of 576 duplicates, 198 articles remained, which were screened by title and abstract, leading to exclusion of 126 records outside the specified timeframe, non-observational designs, or lacking quantitative chemical exposure data.

In the second screening stage, 72 reports were sought for retrieval. Of this, 17 were not retrieved due to data access constraints and paywall restrictions. The 55 articles retrieved were reassessed for eligibility. Twenty-seven articles were excluded at this stage, as they were found to be non-eurocentric and lacking a biomonitoring focus. This process thus yielded 28 distinct and eligible studies, which were included in the final synthesis. A detailed PRISMA flow diagram (Figure 1) is provided below, illustrating this rigorous process.[30]

Figure 1: PRISMA flow diagram

Table 2: Characteristics of included studies

The 28 studies included in the final synthesis were published between 2000 and 2025, encompassing diverse populations across Northern, Western, Southern, and Central Europe. The study designs comprised: Cohort studies: 16 (57%), Case–control studies: 7 (25%), Cross-sectional studies: 2 (7%), Other observational designs (e.g., nested case-control within cohorts): 3 (11%). These studies involved participants from key European countries, including Spain, Denmark, Norway, Sweden, Belgium, France, Greece, the Netherlands, and the UK, reflecting broad geographic coverage.

Sample sizes ranged from small cohorts (~150 participants) to large population-based registries exceeding 50,000 individuals. Age groups covered included children, adolescents, pregnant women, and adults of reproductive age, ensuring representation across critical life stages. Notably, a substantial portion of studies focused on pregnant women and mother–child dyads, reflecting the emphasis on prenatal and early-life exposure to endocrine-disrupting chemicals and their potential health impacts.

Exposure matrices varied by chemical class, as shown in Table 2:
Urine is commonly used for assessing exposure to phthalates and bisphenols, while serum or plasma samples are primarily employed for the measurement of PFAS, PCBs, dioxins, and other persistent organochlorines. In addition, breast milk and cord blood have been applied in several prenatal exposure studies to evaluate maternal and fetal exposure levels. Laboratory methods included gas chromatography-mass spectrometry (GC–MS) and liquid chromatography-mass spectrometry (LC–MS), with trimester- and birth-time-specific sampling sessions. In terms of quality, NOS scores averaged 7.9 out of 9, indicating generally high methodological rigor, with only a minority rated as moderate or low quality.

Prevalence of EDCs in European populations:

Table 3: Summary of biomonitoring data across Europe

BPA: Near-ubiquitous adult exposure; 92% detection, with means of ~0.8–2.5 µg/L depending on age and country. Notably, nearly all adult samples exceeded the EFSA health-based guidance value derived for urine (~11.5 ng/L).[31-33]

Substitutes (BPF/BPS): Emerging but lower prevalence. BPF was detected in 95% of Polish 7-year-olds (~1.0 µg/L), while BPS was less frequently detected (~20%).[28,43]

PFAS: High prevalence across Europe, with measurable serum levels in nearly all teens and adults. PFOS levels average ~2.1 µg/L; PFOA ~1.0 µg/L. Declines observed since peak levels, but persistence remains troubling.[34]

Dioxins & PCBs: Continuously detected in human tissues near industrial zones; data remain sparse relative to more widely monitored chemicals.

Phthalates: While pan-European summary data are limited, urinary DEHP metabolites are widely present (>90%) in European population subsets, warranting comprehensive aggregation in the final synthesis.

This section demonstrates that EDC exposure remains widespread across Europe, with BPA and PFAS concentrations frequently exceeding health-based guidance benchmarks.

Summary of effects of EDC exposure on health outcomes:
This forest plot in Figure 2 visualizes effect sizes from selected studies examining the association between exposure to endocrine-disrupting chemicals (EDCs), primarily PFAS, and various health outcomes.[21,34]

Figure 2: Forest plot: EDC exposure and health outcomes

As shown in Figure 2, PFAS exposure was associated with an increased risk of gestational diabetes (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.10 – 1.91) and type 2 diabetes (OR 1.18, 95% CI 1.05 – 1.32), highlighting consistent metabolic disruption across life stages.[27,39] In contrast, PFAS exposure was inversely associated with TSH levels (β = 0.07, CI −0.02 – 0.16), and positively linked to thyroid hormone levels (β = 0.22, CI 0.01 – 0.44) and cholesterol (β = 4.2 mg/dL, CI 0.8 – 7.7), suggesting potential impacts on endocrine and lipid metabolism.[21,34] These findings support the growing evidence that PFAS compounds can influence metabolic and hormonal pathways, with varying degrees of statistical significance.

Figure 3: Forest plot showing the association between phthalate exposure and BMI Outcomes

Figure 3 clearly shows that phthalate exposure has a significant impact on elevated BMI outcomes. Without significant bias, this clearly supports cohort studies assessing associations between environmental exposures and obesity, BMI, adiposity, or metabolic syndrome. Each dot represents a β coefficient (effect size) with its confidence interval.[35-37]

Heterogeneity metrics for Figure 3 are as follows:

• Cochran’s Q = 28.46
• Degrees of Freedom (df) = 4
• p-value (Q test) < 0.001
• I² = 85.94% (substantial heterogeneity)

Interpretation: Approximately 86% of the variability is attributable to heterogeneity rather than chance.

Publication bias assessment for Figure 3 is as follows:

• Egger’s Intercept: –0.236
• Egger’s p-value: 0.902

Interpretation: No evidence of publication bias detected (p > 0.05)

Figure 4: Heatmap of EDCs and health outcomes

The heatmap in Figure 4 visually reinforces the multifaceted and persistent health risks posed by EDCs across Europe. Darker colors indicate stronger associations based on synthesized study findings. Phthalates and PFAS are more strongly linked with metabolic and developmental outcomes, while bisphenols are prominently implicated in thyroid and reproductive health. These findings emphasize the importance of targeted policy, biomonitoring, and regulatory actions aimed at reducing EDC exposures, especially during vulnerable periods such as pregnancy and early childhood.

Table 4: Key EDCs and selected health outcomes

Table 4 is a concise summary of pooled associations between key EDCs and selected endocrine-related health outcomes from European observational studies.

DerSimonian and Laird’s random-effects meta-analysis was used where applicable. Meta-analyses indicate a positive association with increased adiposity. One report found perinatal phthalate exposure was negatively associated with body mass index (BMI) z-score in children (β = −0.05; 95% CI: −0.10-−0.001) while other observational studies link postnatal phthalate exposure to higher obesity risk among teens and adults.[36,37]

Cohort and cross-sectional-based meta-analyses consistently show PFAS exposure is associated with a higher risk of incident T2DM.[38, 39] A Swedish nested case–control study (2001–2016) reported significant associations between pre-diagnostic PFHpA, PFNA, PFHxS, and later T2DM.[37]

Mixed findings exist, as some large surveys like the Northern Norway Mother–Child Contaminant Study (MISA) and Vogel et al (HBM4EU Phthalates) found inverse or non-linear associations, underscoring complexity.[39] While less robust, some European studies suggest urinary BPA is positively linked to glucose dysregulation and insulin resistance.

PFAS have been implicated in altered thyroid hormones. For example, elevated serum PFAS correlated with abnormal TSH/T4 levels, particularly in women, across several European and U.S. cohorts.[18] Phthalates and BPA were associated with delayed menarche, reduced ovarian reserve, and fertility impairment in women. While an increased risk of endometriosis has been reported in some cohort and case-control studies.[40]

Interpretations:

• Strongest evidence: PFAS exposure shows consistent links with T2DM and thyroid hormone disruption, particularly in prospective cohort designs.[33,37]
• Moderate evidence: Associations of phthalates with obesity/metabolic dysfunction are biologically plausible, though some age and exposure-timing heterogeneity persists.[16,18]
• Emerging evidence: BPA and other phenols point toward metabolic and reproductive impacts, but effect sizes vary across studies.[23]
• Mixture effects and non-linear dose–response: Several studies highlight complex dose–response patterns, e.g., non-monotonic or U-shaped curves for PFAS/diabetes associations.[10]

These findings collectively support targeted subgroup analyses (e.g., by age, sex, geographic region) and further highlight the need for long-term prospective studies in Europe.

Subgroup analyses:
Subgroup analyses revealed notable differences in EDC exposure and associated health outcomes across European regions, age categories, and sex groups.

Table 5: Summary of subgroup findings

Teenagers in Northern and Western Europe exhibited the highest serum PFAS concentrations. A cross-sectional analysis within the HBM4EU study (2014–2021) reported elevated median levels in these regions compared to Eastern and Southern Europe.[43] Approximately 24% of teens in Northern/Western Europe exceeded the European Food Safety Authority (EFSA) health-based guidance value for combined PFAS exposure.[30,44] Urinary BPA and phthalate metabolites were highest in Western European countries, particularly in Northern Italy and France, with positive associations between processed-food consumption (e.g., sauces in plastic containers) and EDC levels among reproductive-age women.[44]

Evidence shows higher urinary phthalate body burdens during early childhood compared to adults. PFAS exposure in teenagers reflects current environmental contamination, with lifestyle factors contributing to variability. A Northern Italian pilot study (median age 36) reported 100% detection rates of BPA and phthalate metabolites, with dietary habits significantly influencing urinary EDC levels.[45,46] Pregnant women in European cohorts frequently exhibited higher bisphenol and phthalate concentrations during the first trimester, reflecting both geographic and behavioral influences.[47]

EDCs such as BPA and phthalates demonstrate sex-dependent effects on puberty timing. For example, BPA is associated with earlier onset in girls and delayed onset in boys, as reported in multiple European and international studies. Phthalate and BPA levels positively correlated with markers of reproductive dysfunction—including delayed menarche, diminished ovarian reserve, and increased endometriosis risk—in predominantly female cohorts.[2,36]

Risk of bias assessment: The methodological quality of the 28 included studies was assessed using the Newcastle–Ottawa Scale (NOS), which evaluates three core domains: selection of study groups, comparability of groups, and ascertainment of exposure or outcome. The NOS assigns a maximum score of 9, with thresholds defined as follows: high quality (7–9), moderate quality (5–6), and low quality (0–4).

• High quality (NOS ≥ 7): 21 studies (75%)
• Moderate quality (NOS 5–6): 6 studies (21%)
• Low quality (NOS ≤ 4): 1 study (4%)

The majority of included studies were rated as high quality, particularly among large cohort and biomonitoring studies with standardized exposure assessments and robust outcome measures. This distribution is consistent with trends observed in comparable systematic reviews of environmental epidemiology, where longitudinal and nationally aligned biomonitoring studies frequently meet higher methodological standards.

Table 6: NOS domain details by study design

Bias impact and sensitivity analyses: As demonstrated in Table 6, the strong methodological performance of cohort studies reinforces the validity of observed associations, particularly for PFAS exposures in relation to type 2 diabetes and thyroid dysfunction. These longitudinal designs provided robust exposure assessments and outcome tracking, minimizing temporal ambiguity. Conversely, observational biases were most pronounced in cross-sectional studies, which predominantly examined outcomes such as obesity and reproductive hormone disruption. These studies were more susceptible to confounding and single-timepoint exposure misclassification.

While 70% of studies achieved high-quality NOS scores, the remaining moderate-to-low quality studies still contributed valuable data for pooled prevalence estimates. Their limitations were explicitly addressed through sensitivity analyses and grade-of-evidence stratification.

Sensitivity and subgroup approaches used:
Risk-stratified meta-analysis: Effect sizes were compared across studies stratified by NOS rating. High-quality studies generally yielded more stable associations with narrower confidence intervals.

Leave-one-out sensitivity tests: Excluding low-quality studies had minimal effect on pooled estimates. However, in BPA obesity models, attenuation of effect sizes by approximately 10–15% was observed.

Meta-regression: Associations between study quality (NOS scores) and effect size were explored. Higher-quality studies tended to report more conservative, yet more statistically robust, estimates.

Overall, the methodological rigor of the included studies, as demonstrated in Table 4.6, was acceptable, with most demonstrating adequate participant selection and validated exposure/outcome ascertainment.

Regional Meta-Regression: PFAS and BPA Exposure Across European Subregions
To explore regional variability in exposure levels, we conducted, as shown in Tables 7 and 8, a simplified meta-regression using harmonized serum concentrations for PFAS and urinary concentrations for BPA. Data were drawn from aligned European biomonitoring datasets (e.g., HBM4EU, Consortium to Perform Human Biomonitoring on a European Scale (COPHES)/DEMOCOPHES, national studies) with standardized methods.[31,32]

Table 7: PFAS exposure (e.g., PFOS, PFOA – Serum ng/mL)

Table 8: BPA exposure (Urinary, GM µg/L, adjusted for creatinine)

Meta-Regression interpretation: PFAS exposure was significantly higher in Northern and Western Europe compared to Southern regions (p < 0.01), with population-level differences reflecting legacy contamination, industrial activity, and regulation history. BPA exposure was highest in Western and Central Europe (p < 0.05), possibly due to dietary packaging, product use, and regulatory enforcement lag.

Implications: Regional disparities highlight the importance of tailored risk communication and policy enforcement.[47] Countries with higher exposure levels may require targeted interventions, including stricter regulation of consumer products, safer alternatives, and improved public awareness.

Summary of key findings:
Widespread exposure across Europe: Human biomonitoring studies consistently demonstrate widespread exposure to EDCs across European populations. BPA was detected in approximately 92% of adult urine samples (geometric mean [GM]: 0.8–2.5 µg/L), while PFAS compounds—particularly PFOS and PFOA were present in over 97% of adolescent serum samples (GM: 2.1 and 1.0 µg/L, respectively). DEHP phthalate metabolites were found in >90% of urine samples across diverse cohorts. Although less frequently measured, dioxins, PCBs, and alternative bisphenols (e.g., BPS, BPF) were also detected, especially in maternal and industrial exposure contexts.[48]

Metabolic health risks:
Phthalates: Prenatal DEHP exposure was associated with modest but statistically significant increases in childhood BMI z-scores (e.g., β = –0.05), while postnatal exposures correlated with elevated obesity risk in both children and adults.

PFAS: Robust cohort evidence links PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA)) with a higher risk of type 2 diabetes and dyslipidemia.[16,23] Associations with obesity in children were more variable, with prenatal exposure often linked to increased waist circumference, while childhood exposure sometimes showed inverse associations.[33,48]

Bisphenols: BPA exposure was associated with glucose and insulin dysregulation, with several studies suggesting links to childhood adiposity. Evidence from animal and cohort studies supports endocrine-mediated metabolic disruption.[16,18]

Thyroid dysfunction: PFAS exposure, especially PFOA and PFNA, was consistently associated with altered thyroid hormone levels (e.g., thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)) in both adolescents and adults.[24] Importantly, these associations often remained significant even after adjustment for confounding factors such as BMI.[16,23]

Reproductive effects: BPA and phthalate exposures were linked to delayed menarche, reduced ovarian reserve, subfertility, and increased risk of endometriosis. Evidence also points to sex-specific disruptions in pubertal timing—e.g., earlier puberty in girls and delayed onset in boys exposed to BPA.[36,45]

Non-linear and complex exposure–response patterns: Some PFAS-related health outcomes exhibited non-linear or U-shaped dose–response relationships.[2,33] For example, both low and high PFAS exposures were sometimes associated with reduced BMI, suggesting complex interactions.[21,34] These effects varied by sex, age, exposure timing, and presence of co-exposures, underscoring the need for nuanced interpretation.[24,35]

Integrated overview and implications:
The evidence indicates a persistent chemical burden across Europe, with near-ubiquitous exposure to BPA, phthalates, PFAS, and other EDCs.[49] The strongest and most consistent associations were observed between PFAS and metabolic or thyroid outcomes, particularly in longitudinal studies. Associations involving phthalates and BPA with obesity and reproductive endpoints align with known biological mechanisms, including endocrine mimicry and PPAR-γ activation, though effect sizes are generally modest.[4,36]

Marked heterogeneity was observed across studies, highlighting the influence of demographic factors (e.g., age, sex), timing of exposure, and regional context.[24,47] These findings reinforce the need for stratified analyses, mixture modeling, and continued investment in longitudinal biomonitoring and exposure prevention policy across Europe.

This systematic review and meta-analysis synthesized evidence from European observational studies published between 2000 and 2025 on the prevalence of EDCs and their associations with endocrine-related health outcomes. Our findings confirm widespread human exposure to various EDCs, including BPA, phthalates, PFAS, and legacy pollutants such as PCBs and dioxins.

Exposure levels varied geographically, with higher PFAS concentrations observed in Northern and Western Europe and increased phthalate exposure among children and adolescents. Importantly, epidemiological evidence links EDC exposure to increased risks of obesity, type 2 diabetes, thyroid dysfunction, reproductive disorders, and gestational diabetes mellitus. Although heterogeneity across studies exists, meta-analytic results suggest moderate but consistent associations between EDC levels and adverse endocrine outcomes.

Implications for policy and practice: The findings underscore the urgent need for enhanced regulatory oversight and public health interventions in Europe to reduce human exposure to harmful EDCs. Despite existing EU chemical safety frameworks, such as REACH and the Chemicals Strategy for Sustainability, ongoing exposure, particularly to PFAS and phthalates, remains.

Policy actions should include:

• Stricter limits on EDC use and emissions, with continuous revision based on emerging biomonitoring data.
• Increased transparency and public reporting of EDC presence in consumer products and the environment.
• Promotion of safer chemical alternatives in manufacturing and agriculture.
• Targeted risk communication and prevention programs focused on vulnerable populations such as children, pregnant women, and workers in high-exposure industries.
• Integration of human biomonitoring data into health surveillance systems to enable timely risk assessment and policy adjustments.
• Clinicians should be aware of environmental EDC exposures as potential contributing factors to endocrine and metabolic diseases and incorporate this knowledge into preventive care and patient education.

Strengths of the study: This review followed rigorous PRISMA guidelines to identify and synthesize a broad range of European observational studies spanning two decades. Meta-analytic quantification enabled estimation of overall effect sizes, adding statistical power and precision to individual study findings. Furthermore, our synthesis covered children, adults, pregnant women, and a spectrum of EDC classes, improving generalizability across Europe. By restricting European studies, this review provides actionable regional insights relevant to EU policy frameworks.

Limitations of the study: Differences in biomonitoring methods, chemical measurement techniques, and exposure windows limited direct comparability. Negative or null results might be underrepresented. Most studies were cross-sectional, which restricts causal inference regarding EDC exposure and health outcomes. Furthermore, novel and less-studied compounds such as replacement plasticizers and newer variants of PFAS appeared to be slightly underrepresented. Inclusion of solely English-language peer-reviewed studies may exclude relevant data published in other languages or grey literature.

Recommendations for future research: This systematic review and meta-analysis was groundbreaking. It exposed the effects of EDC within the European population over the past two and a half decades. However, we strongly recommend longitudinal cohort studies in delineating more aspects of this public health issue. Longitudinal cohort studies are key to better elucidating temporal and causal relationships between EDC exposure and endocrine health outcomes.

Research on combined exposures to multiple EDCs is needed to reflect real-world environmental conditions. It is also vital to focus on sensitive groups, including infants, pregnant women, and occupational cohorts. Standardization of biomonitoring methods is essential to improve comparability across studies and regions.

Finally, evaluation of regulatory impact is key. This involves monitoring trends post-implementation of new policies to assess effectiveness in reducing exposures and health burdens. It is also vital to promote broader geographic representation. We encourage data collection from underrepresented Eastern and Southern European countries.

This systematic review and meta-analysis highlight pervasive exposure to endocrine-disrupting chemicals across European populations and their association with significant adverse endocrine and metabolic health outcomes. Despite regulatory advances, ongoing exposure to compounds such as PFAS and phthalates demands sustained policy attention and preventive strategies. Enhancing biomonitoring efforts, advancing epidemiological research, and translating findings into effective regulation and public health action are critical to mitigating the endocrine-related disease burden in Europe.

We declare that this work is original. Data were sourced and referenced in line with ethical standards of the General Data Protection Regulation (GDPR). We acknowledge the use of publicly accessible scientific databases and repositories, including CrossRef, PubMed, Cochrane Library, Scopus, and Google Scholar, for providing the peer-reviewed literature that formed the foundation of this paper. We also thank Evidence Synthesis Hackathon for access to PRISMA 2020 software.

None

Corresponding Author:
Chinua Onyebuchi
Department of Medicine
Institute of Medicine, Royal College of Physicians of Ireland, Dublin, Ireland
Email: chinuaonyebuchi@gmail.com

Co-Authors:
Ifeanyichukwu MUOGBO
Department of Medicine
University of Ibadan, College of Medicine, Nigeria

Christopher Okolo CHUKWURAH
Department of Medicine
University of Nigeria, Enugu, Nigeria

Madina ABDULKADIR
Department of Medicine
University of Ibadan, College of Medicine, Nigeria

Oghenekevwe Princess GORDON
Department of Medicine
Niger Delta University, Bayelsa State, Nigeria

Susan Ayobami OGUNDARE
Department of Medicine
Ladoke Akintola University of Technology, Nigeria

Innocent AGABA
Department of Paediatrics
Modibbo Adama University Teaching Hospital, Yola, Nigeria

All authors contributed to the Conceptualization, Investigation, and Data Curation by acquiring and critically reviewing the selected articles. They were collectively involved in the Writing – Original Draft preparation and Writing – Review & Editing to refine the manuscript. Additionally, all authors participated in the Supervision of the work, ensuring accuracy and completeness. The final manuscript was approved by all named authors for submission to the journal.

The study was conducted in accordance with the principles of academic integrity and transparency. Data were sourced and referenced in line with ethical standards of the General Data Protection Regulation (GDPR).

The authors declare no conflict of interest.

None

https://doi.org/10.63096/medtigo30612310

Onyebuchi C, Muogbo I, Chukwurah CO, et al. Endocrine Disrupting Chemicals and Health in Europe: A Systematic Review and Meta-Analysis. medtigo J Pharmacol. 2025;2(3):e30612310. doi:10.63096/medtigo30612310 Crossref