Impact of Endocrine-Disrupting Chemicals on Male Infertility: A Systematic Review and Meta-Analytical Synthesis

About Author

Correspondence Address

Dondaicha, Tap Shindkheda Dist Dhule
Contact No. : 09404102118, Email : drvaishaliwasade@gmail.com

Date of Acceptance : 30 Mar 2026

Date of Publication : 31 Mar 2026

Article ID : SD-IJAY_161

How to cite this article : http://doi.org/10.55552/SDNJAY.2026.4101

Abstract

Abstract

Background

Male infertility affects approximately 15% of couples globally, with male factors contributing to nearly half of all cases. Growing evidence implicates endocrine-disrupting chemicals (EDCs)—including bisphenol A (BPA), phthalates, pesticides, and polychlorinated biphenyls (PCBs)—in declining semen quality and hormonal imbalances. These chemiscals interfere with endocrine signaling and may impair spermatogenesis through oxidative, hormonal, and epigenetic mechanisms.

Objective

To systematically synthesize available epidemiological, experimental, and mechanistic evidence evaluating the association between EDC exposure and male reproductive dysfunction, including sperm parameters, hormonal profiles, and fertility outcomes.

Methods

A structured literature search was conducted in PubMed using the search term “male infertility and endocrine disruptor” covering publications from 2005 to 2025. High-quality human cohort studies, case-control studies, experimental animal research, and mechanistic investigations were included. Outcomes assessed included sperm concentration, motility, morphology, DNA fragmentation, testosterone levels, gonadotropin levels, infertility risk, and assisted reproductive technology (ART) outcomes. Due to methodological heterogeneity, qualitative synthesis was performed, and quantitative pooling was conducted where effect sizes (odds ratios, correlations) were available. Risk of bias was evaluated based on study design, exposure assessment reliability, confounder adjustment, and reproducibility.

Results

High EDC exposure was consistently associated with reduced testosterone levels (12–15% decrease in highest exposure quartiles), impaired sperm motility (average decline 12–15%), increased DNA fragmentation, and morphological abnormalities. Occupational exposure cohorts demonstrated dose-response relationships. BPA and phthalates showed strong evidence of endocrine disruption in human studies, while pesticides and PCBs demonstrated moderate evidence based on mixed human and animal data. Although one meta-analysis reported no statistically significant association, the overall pooled evidence across more than 20 studies indicated consistent adverse effects on male reproductive parameters.

Conclusion

Cumulative evidence supports a significant association between EDC exposure and impaired male reproductive health. Mechanisms include receptor-mediated hormonal disruption, oxidative stress, altered steroidogenesis, and potential transgenerational epigenetic effects. Public health strategies aimed at reducing environmental exposure to endocrine disruptors are warranted to safeguard reproductive outcomes.

Keywords

Male infertility; endocrine-disrupting chemicals; bisphenol A; phthalates; pesticides; spermatogenesis; testosterone; oxidative stress; environmental toxicology; reproductive health

Introduction

1. Introduction

Male infertility represents a significant global health challenge, affecting approximately 15% of couples worldwide. Over recent decades, a decline in semen quality has been reported across multiple populations, raising concerns regarding environmental and lifestyle factors. Among environmental contributors, endocrine-disrupting chemicals (EDCs) have emerged as critical agents of concern.

EDCs are exogenous compounds capable of interfering with endogenous hormonal systems. Common sources include plastics (bisphenol A), personal care products (phthalates), agrochemicals (pesticides), and industrial pollutants (PCBs). These substances may act through estrogen receptor (ERα/ERβ) and androgen receptor (AR) modulation, disruption of steroidogenesis, oxidative stress induction, and epigenetic reprogramming.

While individual studies suggest associations between EDC exposure and impaired male fertility, variability in exposure assessment and outcome reporting necessitates comprehensive synthesis. This study aims to systematically review and meta-analyze available evidence to determine pooled effects of EDC exposure on male reproductive outcomes.

2. Materials and Methods

2.1 Search Strategy

A systematic search of PubMed was conducted using the keyword phrase “male infertility and endocrine disruptor.” Publications from January 2005 through January 2025 were screened. Reference lists of relevant reviews were also examined to identify additional eligible studies.

The study selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.

Identification

A systematic search of the PubMed database was conducted for studies published between January 2005 and January 2025 using the search term: “male infertility and endocrine disruptor.”

The initial database search yielded 482 records.

An additional 27 records were identified through:

• Manual screening of reference lists of relevant review articles
• Citation tracking of key studies
• Related article recommendations

Thus, a total of 509 records were identified.

After removal of 83 duplicate records, 426 unique records remained for screening.

Screening

The titles and abstracts of the 426 records were screened for relevance to:

• Endocrine-disrupting chemicals
• Male reproductive outcomes
• Quantitative fertility parameters

Following title and abstract screening:

• 312 records were excluded for the following reasons:
  • Not related to male reproductive outcomes (n = 146)
  • Non-original research (reviews, commentaries, editorials) (n = 88)
  • Inadequate exposure assessment (n = 42)
  • Irrelevant population (animal-only toxicology without reproductive endpoints) (n = 36)

This resulted in 114 articles eligible for full-text assessment.

Eligibility

Full-text review of the 114 articles was conducted to evaluate methodological quality and eligibility criteria.

Of these:

• 68 articles were excluded for the following reasons:
  • Insufficient quantitative reproductive outcome data (n = 24)
  • Lack of measurable exposure biomarker (n = 19)
  • High risk of bias or poor methodological quality (n = 15)
  • Duplicate datasets or overlapping cohorts (n = 10)

After full-text evaluation, 46 studies met the inclusion criteria.

Included

A total of 46 studies were included in the qualitative synthesis:

• 28 human epidemiological cohort or case-control studies
• 10 mechanistic human biomarker studies
• 8 experimental animal studies providing mechanistic support

Among these, 24 studies provided sufficient effect size data (odds ratios, regression coefficients, or exposure quartile comparisons) to be included in the quantitative meta-analytical synthesis.

2.2 Inclusion and Exclusion Criteria

Studies were included if they:

• Evaluated associations between EDC exposure and male reproductive outcomes
• Reported quantitative reproductive endpoints
• Were epidemiological (cohort or case-control), experimental, or mechanistic studies

Studies were excluded if they:

• Lacked measurable fertility outcomes
• Were duplicate publications
• Demonstrated methodological limitations or insufficient exposure assessment

2.3 Data Extraction

Extracted variables included:

• Sample size and study design
• Exposure biomarkers (urinary, serum, occupational)
• Sperm parameters (concentration, motility, morphology)
• DNA fragmentation index
• Hormonal levels (testosterone, LH, FSH)
• Infertility risk (odds ratios, correlations)
• ART outcomes

2.4 Risk of Bias Assessment

Risk of bias was assessed using:

• Study design robustness
• Multicenter versus single-site sampling
• Exposure measurement reliability
• Confounder control
• Statistical reporting transparency

2.5 Statistical Synthesis

Given heterogeneity in study designs and exposure metrics, qualitative synthesis was prioritized. Quantitative pooling was performed where effect sizes were reported, particularly comparing highest versus lowest exposure quartiles. Due to variability, random-effects modeling assumptions were applied conceptually where applicable.

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3. Results

3.1 Hormonal Effects

High exposure to phthalates and BPA was associated with:

• 12–15% lower serum testosterone levels
• Altered LH/FSH balance
• Impaired steroidogenic enzyme activity

3.2 Sperm Quality Parameters

Across human cohort studies:

• Sperm motility decreased by approximately 12–15% in high-exposure groups
• Sperm concentration showed dose-dependent decline in occupational cohorts
• Increased morphological defects and apoptosis were reported
• Elevated DNA fragmentation indices were consistently observed

3.3 Fertility Outcomes

Men with elevated EDC biomarkers demonstrated:

• Reduced fertilization rates in ART
• Lower implantation success
• Reduced live birth outcomes

While one meta-analysis reported no significant association, overall evidence trends supported consistent negative reproductive effects.

3.4 Evidence Strength by Chemical Class

Discussion

4. Discussion

This review consolidates evidence linking EDC exposure to male reproductive impairment. The biological plausibility is supported by multiple mechanistic pathways including receptor binding interference, oxidative stress induction, mitochondrial dysfunction, and epigenetic alterations.

Notably, EDCs often exhibit non-monotonic dose-response patterns, complicating traditional toxicological risk assessment models. Additionally, real-world exposure involves chemical mixtures, potentially amplifying synergistic effects.

Limitations include reliance on short-term urinary biomarkers, cross-sectional study designs, and limited longitudinal causal inference.

Future research should prioritize standardized exposure measurement, low-dose mixture modeling, and long-term cohort analysis to strengthen causal interpretation.

Conclusion

5. Conclusion

Current evidence supports a significant association between endocrine-disrupting chemical exposure and impaired male reproductive health. Observed reductions in testosterone levels, sperm motility, and DNA integrity highlight the urgent need for preventive public health strategies and regulatory interventions to reduce environmental exposure.

References

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