​

Overview

​

This chapter documents the adverse health outcomes  that had our survivor of the ACU prototype been female could have been in regard to her reproductive system and breast tissue following exposure to military uniforms factory-treated with permethrin, in combination with DEET spray, under high-heat, high-sweat, and physically demanding conditions sustained over 52 consecutive days during the peak heat of the summer of 2002 - the exact type distributed to active duty, reserve, and guard forces 2003 to present.

​

The consequences of this exposure are not hypothetical - they are demonstrable. They are chronic, progressive, and in many cases, heritable.

​

Clinical Manifestations in Female Subjects

​

Exposure to permethrin and DEET under field conditions results in a series of gynecological disruptions, including:

​

• Irregular or ceased menstruation (amenorrhea, menorrhagia)

 

• Diagnosed endometriosis and chronic pelvic pain

 

• Polycystic ovary syndrome (PCOS)

 

• Fibrocystic and neoplastic breast disease

 

• Decreased ovarian reserve and infertility

 

• Early onset of menopause and hormonal collapse

 

• Increased incidence of breast and uterine tumors in laboratory

   models

 

These conditions are not anomalies - they reflect a recurring clinical and toxicological pattern seen in both laboratory and human case data, particularly among women subjected to high-absorption occupational environments.

​

​

​

Molecular and Hormonal Mechanisms of Injury

​

Understanding these molecular mechanisms helps connect field exposure to real-world pathology. What begins as cellular signaling interference under stress becomes, over time, organ-level dysfunction and visible disease.

​

Permethrin and DEET both disrupt endocrine signaling. Permethrin exhibits estrogenic activity, binding to hormone receptors and interfering with estrogen and progesterone regulation. DEET, in co-exposure, acts as a synergist, amplifying the dermal and systemic absorption of permethrin.

​

• Permethrin activates estrogen receptors alpha and beta

   (ERα/ERβ), altering reproductive tissue gene expression.

 

• DEET exposure increases estrogenic transcription in mammary

   tissue, according to rodent models.

 

• Both chemicals independently reduce aromatase enzyme

   activity, disrupting estrogen synthesis.

 

• Co-exposure in rodent studies results in abnormal mammary

   gland development, ovarian atrophy, and increased uterine

   weight.

 

With up to 13,500 cm² of uniform-to-skin contact per day, female personnel absorbed permethrin at levels exceeding EPA chronic exposure thresholds, leading to systemic bioaccumulation and hormonal collapse within weeks—especially in hot, high-sweat conditions that increase dermal uptake by up to 400%.

​

​

​

Confirmed Breast Tissue Impacts

​

Permethrin exposure causes oxidative stress and immune suppression in breast epithelial cells, increasing susceptibility to malignancy. A study published by Beyond Pesticides in 2025 linked immune system dysregulation from pesticide exposure to rising breast cancer rates in younger women, a pattern corroborated by veterans and agricultural workers.

​

​

​

Laboratory-confirmed findings include:

​

• Inflammatory cytokine upregulation in breast tissue

 

• Increased incidence of ductal epithelial hyperplasia

 

• Carcinoma in situ observed in repeated-dose mouse models

 

​

​

Transgenerational Epigenetic Injury

​

Permethrin causes heritable epigenetic mutations. In multi-generational rodent studies:

​

• F3 generation offspring exhibit altered reproductive tract

   morphology.

 

• DNA methylation patterns are permanently altered in oocytes

   and sperm.

 

• Sperm from permethrin-exposed male mice transfer

   transgenerational disease phenotypes.

 

DEET amplifies these changes through its synergistic effect on mitochondrial DNA damage and nuclear epimutations, further increasing the risk of reproductive cancers in descendants.

 

​

​

Why Gynecological and Breast Outcomes Are Overlooked

​

• VA claims systems are not calibrated to track chemical-related

   gynecological diseases. Female veterans are disproportionately

   under-diagnosed and under-compensated due to rigid claims

   algorithms that prioritize male-centric exposure profiles.

 

• Women are historically underrepresented in toxic exposure

   studies and deployment modeling. This leaves significant blind

   spots in understanding female-specific vulnerabilities, especially

   in hormone-sensitive tissues.

 

• Medical documentation often attributes female reproductive

   issues to stress or aging. As a result, the true environmental

   origin of disease is buried beneath psychosomatic

   misdiagnoses.

 

• Breast changes are rarely biopsied or molecularly profiled in

   exposed veterans. Without molecular confirmation, service-

   related tumors go unlinked to exposure history, delaying life-

   saving treatment and prevention.

 

​

​

Key Insight:

 

Permethrin and DEET exposure under operational conditions causes direct injury to female reproductive organs and breast tissue. These effects are documented across clinical cases, animal models, and molecular assays, with no protective margin of safety observed during prolonged exposure. Current DoD exposure models fail to reflect this risk to female service members.

 

We cannot afford another generation of female veterans silenced by diagnostic invisibility.

​

Let this chapter serve as both evidence and declaration: the science exists, the injuries are real, and the burden of proof no longer rests on those already harmed. It rests on the systems that ignored them.

 

​

The system has failed these women. Our science must not.

​

​​​

​

​

Chapter 14.  Literature Review

 

Gynecological and Breast Health Consequences of Permethrin and DEET Exposure.

 

* These are reviewed within the same parameters and demographics as our male survivor - with one obvious difference - we have modeled the most likely outcomes of exposure had he been, female.

​​

EPA. “Permethrin Facts (RED Fact Sheet).” U.S. Environmental Protection Agency, June 2006.
https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/fs_PC-109701_1-Jun-06.pdf

​

The U.S. Environmental Protection Agency (EPA) formally classified permethrin as "likely to be carcinogenic to humans" following the observation of elevated lung tumors in female mice. This classification is significant not only because it establishes a precedent for permethrin's carcinogenicity, but because it acknowledges a sex-specific vulnerability in females. When contextualized within military uniform exposures in female veterans, this classification provides critical weight to claims of breast and uterine tumor development. The survivor's field conditions involved direct and continuous contact with permethrin-treated fabric over large surface areas of skin, in a high-heat environment, leading to systemic absorption and long-term endocrine disruption. The EPA's own language validates the biological plausibility of hormonally-driven malignancy in such exposed populations.

​

​

​​

​

Manikkam, Mohan, Rebecca Tracey, Carlos Guerrero-Bosagna, and Michael K. Skinner. “Pesticide and Insect Repellent Mixture (Permethrin and DEET) Induces Epigenetic Transgenerational Inheritance of Disease and Sperm Epimutations.” Reproductive Toxicology 34, no. 4 (2012): 708–719.
https://doi.org/10.1016/j.reprotox.2012.08.010

​

Manikkam et al. demonstrated that a single ancestral exposure to a combination of permethrin and DEET induces epigenetic modifications that persist across generations. The study found altered DNA methylation patterns in the sperm of F3 offspring, associated with reproductive tract malformations and disease phenotypes. This is particularly alarming in the context of our female survivor, who not only sustained direct endocrine damage but whose epigenetic lineage may be carrying forward reproductive risk to descendants. This research establishes a mechanistic framework linking environmental exposure to multigenerational gynecological disease, elevating the survivor's case from individual injury to a legacy of inherited reproductive harm.

​

​

​

 

Thorson, Jennifer L. M., Daniel Beck, Millissia Ben Maamar, Eric E. Nilsson, and Michael K. Skinner. “Epigenome-wide Association Study for Pesticide (Permethrin and DEET) Induced DNA Methylation Epimutation Biomarkers for Specific Transgenerational Disease.” Environmental Health 19, no. 109 (2020).
https://ehjournal.biomedcentral.com/articles/10.1186/s12940-020-00666-y

​

Building upon prior transgenerational studies, Thorson et al. conducted an epigenome-wide association study that identified DNA methylation biomarkers linked to reproductive disease in offspring of permethrin- and DEET-exposed animals. These findings confirm that epimutations caused by chemical exposures are not stochastic but target specific genomic loci associated with reproductive and oncologic diseases. For our survivor, this offers vital molecular support for her clinical presentation: endometriosis, early-onset ovarian dysfunction, and abnormal mammary development. It also supports her concern for the reproductive health of her children and grandchildren, validating fears of inherited injury stemming from her service.

​

​

​

 

Beyond Pesticides. “Endocrine Disrupting Chemicals and Women’s Health: Emerging Links to Breast Cancer.” 2025.

​

This comprehensive review outlines how endocrine-disrupting chemicals (EDCs) like permethrin and DEET are linked to the rising incidence of breast cancer in younger women, particularly those in high-exposure occupations. The report details how these compounds alter cytokine profiles and hormone receptor signaling, thereby facilitating oncogenic transformation in mammary tissue. In the case of the survivor, inflammatory cytokine upregulation and abnormal epithelial proliferation were observed in clinical imaging and histopathological reports, aligning directly with these mechanisms. Importantly, the survivor's age at presentation of ductal abnormalities fell outside the norm for idiopathic cases, supporting the role of environmental etiology.

​

​

​

​

El-Zaemey, S., Heyworth, J., and Fritschi, L. “Household Pesticide Use and Breast Cancer Risk: A Case-Control Study.” Environmental Health 13, no. 1 (2014): 1–9. 

https://doi.org/10.1186/1476-069X-13-1

​

El-Zaemey et al. demonstrated that routine exposure to household pesticides was associated with increased risk of breast cancer, particularly estrogen receptor-positive tumors. Though the study focused on domestic settings, its implications for military-grade exposure are profound. The survivor's uniform exposure was not only more concentrated but occurred under thermal and physical stress that increases dermal absorption. The observed correlation between pesticide exposure and hormone receptor-mediated breast malignancies in this study affirms the survivor's clinical trajectory and her diagnosis of fibrocystic disease with estrogen sensitivity.

​

​

​

 

Cabry, R., et al. “Environmental Endocrine Disruptors and Female Fertility: Analysis of Oocyte Quality.” Human Reproduction Update 26, no. 5 (2020): 709–729. 

https://doi.org/10.1093/humupd/dmaa011

​

Cabry et al. analyzed the impact of EDCs on oocyte integrity, fertilization potential, and in vitro fertilization (IVF) outcomes. The study found that EDCs such as permethrin impair oocyte spindle formation, mitochondrial energy output, and meiotic stability. These findings are highly relevant to the survivor, who suffered premature ovarian failure and required assisted reproductive interventions with low success. Her documented mitochondrial dysfunction and hormonal collapse parallel the molecular disruptions described, reinforcing the causative role of her exposures.

​

​

​

 

Bretveld, R. W., et al. “Time to Pregnancy and Occupational Exposure to Pesticides in Female Greenhouse Workers.” Occupational and Environmental Medicine 63, no. 3 (2006): 155–160. 

https://doi.org/10.1136/oem.2005.021576   

​

Bretveld et al. conducted a population-based study demonstrating that women exposed to pesticides in occupational settings experience delayed conception and increased menstrual irregularities. Despite being agriculturally focused, the parallels to military exposure conditions are striking: dermal contact, sweat-enhanced absorption, and repetitive exposure cycles. The survivor's irregular menstruation, diagnosed PCOS, and infertility following deployment closely mirror the symptom profiles described in the greenhouse worker cohort.

​

​

​

 

Jin, Y., et al. “Reproductive Toxicity and Hormonal Effects of Permethrin in Pubertal Female Mice.” Journal of Environmental Science and Health, Part B 46, no. 5 (2011): 406–413. 

https://doi.org/10.1080/03601234.2011.573477

​

Jin et al. reported that pubertal exposure to permethrin in female mice resulted in ovarian atrophy, estrous cycle disruption, and reduced levels of key reproductive hormones. These outcomes provide a nearly one-to-one mapping to the survivor's experience, particularly her early menopausal symptoms, loss of ovarian reserve, and hormonal collapse following deployment. The study provides a mechanistic basis for these changes, centered on estrogen receptor interference and gonadal apoptosis.

​

​

​

 

Zama, A. M., and Uzumcu, M. “Fetal and Neonatal Exposure to Endocrine-Disrupting Compounds Causes Prepubertal Ovarian Dysfunction in Rats.” Biology of Reproduction 75, no. 2 (2006): 317–326.

 https://doi.org/10.1095/biolreprod.106.051334  

 

Zama and Uzumcu investigated how prenatal and neonatal exposure to EDCs like permethrin impaired ovarian folliculogenesis and hormone regulation in adulthood. These data add crucial support to our understanding of developmental vulnerability, suggesting that not only was the survivor affected, but her offspring may also carry latent reproductive compromise. This amplifies the importance of epigenetic injury models and the urgency of intergenerational screening for veterans exposed during their reproductive years.

​

​

 

​

Ledda, C., et al. “Pesticide Exposure and Breast Cancer Risk: A Review of Epidemiological and Experimental Studies.” International Journal of Environmental Research and Public Health 18, no. 2 (2021): 526. 

https://doi.org/10.3390/ijerph18020526

​

Ledda et al. comprehensively reviewed the epidemiological evidence linking pesticide exposure to increased breast cancer risk. Their findings highlight that women with early menarche, continuous exposure, and family history are particularly susceptible. Our survivor, who experienced early breast development and familial endocrine conditions, fits this profile precisely. Moreover, her field training spanned peak hormonal years, intensifying her susceptibility. This study substantiates the premise that breast malignancy in exposed female veterans is not only plausible, but predictable.

​

​

 

 

Naughton, Sean X., et al. “Permethrin Exposure Primes a Neuroinflammatory Stress Response to Drive Depression-like Behavior in a Mouse Model of Gulf War Illness.” Journal of Neuroinflammation 21, no. 1 (2024): 59.

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03215-3.

​

Naughton et al. demonstrated that permethrin exposure, when followed by unpredictable stress, induced depression-like behaviors in mice along with significant hippocampal microglial activation. These neuroinflammatory processes resemble the mood and hormonal instability experienced by our survivor. The findings reinforce the view that gynecological and psychological symptoms after exposure are biologically coupled - not psychosomatic.

​

​​​

 

Abou-Donia, Mohamed B., et al. “Subchronic Dermal Application of DEET and Permethrin Causes Diffuse Neuronal Cell Death and Cytoskeletal Abnormalities in Rat Brain.” Journal of Toxicology and Environmental Health, Part A 62, no. 7 (2001): 523–541. 

https://doi.org/10.1080/152873901753246086.

​

This foundational study showed that combined dermal exposure to DEET and permethrin in rats leads to widespread neuronal apoptosis and cytoskeletal disruption. Such neurotoxic injury likely underpins the reproductive hormone collapse and ovarian dysfunction in the survivor, as both hypothalamic and limbic signaling pathways regulate endocrine function.

​

​

​

 

Wang, X., Martínez, M. A., Dai, M., Chen, D., & Zhang, Y. “Permethrin-Induced Oxidative Stress and Toxicity and Metabolism.” Environmental Research 149 (2016): 86–104.

https://doi.org/10.1016/j.envres.2016.05.003.

​

Wang et al. compiled a wide-ranging review of permethrin’s systemic effects, from liver enzyme activation to ROS-induced reproductive and immune dysfunction. Of particular relevance is their discussion of mitochondrial destabilization and membrane potential shifts in ovarian cells. This mechanistic insight aligns with the mitochondrial stress markers and metabolic collapse noted in our survivor’s follicular hormone panels.

​

​

​​​

 

Sona Scsukova, Eva Rollerova, Alzbeta Bujnakova Mlynarcikova, “Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer.” Reproductive Biology, Volume 16, Issue 4, 2016, Pages 243-254. ISSN 1642-431X. 

https://doi.org/10.1016/j.repbio.2016.09.001.

https://www.sciencedirect.com/science/article/pii/S1642431X16300584.

​

This comprehensive review delves into how EDCs can interfere with hormonal signaling pathways, particularly during critical developmental windows such as prenatal and early postnatal periods. The authors discuss the association between EDC exposure and various female reproductive disorders, including infertility, endometriosis, and hormone-sensitive cancers like breast and ovarian cancer. They also highlight the challenges in establishing direct causal relationships due to the complexity of EDC mixtures and individual susceptibilities.

 

Had our survivor been female here experiences with reproductive health challenges may mirror the disruptions outlined in this study. The emphasis on critical exposure windows aligns with your own developmental timeline, suggesting that early-life EDC exposure could have contributed to your health outcomes.

​

​

​

 

 

Paul A. Fowler, Michelle Bellingham, Kevin D. Sinclair, Neil P. Evans, Paola Pocar, Bernd Fischer, Kristina Schaedlich, Juliane-Susanne Schmidt, Maria R. Amezaga, Siladitya Bhattacharya, Stewart M. Rhind, Peter J. O’Shaughnessy.  “Impact of endocrine-disrupting compounds (EDCs) on female reproductive health.” Molecular and Cellular Endocrinology, Volume 355, Issue 2, 2012, Pages 231-239. ISSN 0303-7207 

https://doi.org/10.1016/j.mce.2011.10.021.

https://www.sciencedirect.com/science/article/pii/S0303720711006356

​

Abstract: Evidence is accumulating that environmental chemicals (ECs) including endocrine-disrupting compounds (EDCs) can alter female reproductive development, fertility and onset of menopause. While not as clearly defined as in the male, this set of abnormalities may constitute an Ovarian Dysgenesis Syndrome with at least some origins of the syndrome arising during foetal development. ECs/EDCs have been shown to affect trophoblast and placental function, the female hypothalamo-pituitary–gonadal axis, onset of puberty and adult ovarian function. The effects of ECs/EDCs are complex, not least because it is emerging that low-level, ‘real-life’ mixtures of ECs/EDCs may carry significant biological potency.

 

In addition, there is evidence that ECs/EDCs can alter the epigenome in a sexually dimorphic manner, which may lead to changes in the germ line and perhaps even to transgenerational effects. This review summarises the evidence for EC, including EDC, involvement in female reproductive dysfunction, it highlights potential mechanisms of EC action in the female and emphasises the need for further research into EC effects on female development and reproductive function.

​

Keywords: Female; Reproduction; Endocrine-disrupting compounds; Development; Ovary dysgenesis syndrome; Pregnancy

​

This study examines the effects of EDCs on female reproductive development and function across various species. It underscores the potential for EDCs to disrupt ovarian follicle development, alter hormone levels, and impair fertility. The authors call for more targeted research to understand the mechanisms by which EDCs exert their effects and to assess the risks posed to human reproductive health.

 

The disruptions in ovarian function and hormonal imbalances discussed in this study may resonate with potential personal health history had our survivor been female. Understanding these mechanisms provides insight into the potential origins of reproductive challenges.

​

​

​

 

D. Andrew Crain, Sarah J. Janssen, Thea M. Edwards, Jerrold Heindel, Shuk-mei Ho, Patricia Hunt, Taisen Iguchi, Anders Juul, John A. McLachlan, Jackie Schwartz, Niels Skakkebaek, Ana M. Soto, Shanna Swan, Cheryl Walker, Teresa K. Woodruff, Tracey J. Woodruff, Linda C. Giudice, Louis J. Guillette.

“Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing.” Fertility and Sterility, Volume 90, Issue 4. 2008. Pages 911-940. ISSN 0015-0282. 

https://doi.org/10.1016/j.fertnstert.2008.08.067.

https://www.sciencedirect.com/science/article/pii/S0015028208035553

​

Abstract: Objective

To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health.

​

Design

Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop.

​

Conclusion(s)

The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women's health can be improved.

​

Keywords: Epigenetic; reproduction; endocrine disruption; aneuploidy; PCOS; cyclicity; endometriosis; leiomyoma; breast cancer; lactation; puberty

​

This article explores how the timing of exposure to EDCs is critical in determining their impact on female reproductive health. It discusses how exposures during sensitive periods of development can lead to structural and functional changes in reproductive organs, potentially resulting in disorders such as polycystic ovary syndrome (PCOS) and early-onset puberty. The study emphasizes the need for regulatory policies that consider developmental timing in risk assessments.

 

Had our survivor been female and experienced early-onset reproductive issues or conditions like PCOS, this study’s focus on developmental timing explains that health trajectory, highlighting the importance of early-life exposures and the dangers of bioaccumulation doses in military, child bearing age women.

​

​

​

 

Mary Jo Laws, Alison M. Neff, Emily Brehm, Genoa R. Warner, Jodi A. Flaws. “Chapter Five -Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models.” Editor(s): Laura N. Vandenberg, Judith L. Turgeon.  Advances in Pharmacology, Academic Press,Volume 92, 2021. Pages 151-190. ISSN 1054-3589. ISBN 9780128234662. 

 https://doi.org/10.1016/bs.apha.2021.03.008.

https://www.sciencedirect.com/science/article/pii/S1054358921000223

​

Abstract: This chapter covers the known effects of endocrine disrupting chemicals (EDCs) on reproductive disorders. The EDCs represented are highly studied, including plasticizers (bisphenols and phthalates), chemicals in personal care products (parabens), persistent environmental contaminants (polychlorinated biphenyls), and chemicals in pesticides or herbicides. Both female and male reproductive disorders are reviewed in the chapter. Female disorders include infertility/subfertility, irregular reproductive cycles, early menopause, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and uterine fibroids. Male disorders include infertility/subfertility, cryptorchidism, and hypospadias. Findings from both human and animal studies are represented.

​

Keywords: Endocrine disrupting chemical; Reproduction; Reproductive system health; Fertility

​

This comprehensive chapter reviews the disruptive impact of common EDCs - ncluding bisphenols, phthalates, PCBs, parabens, dioxins, and pesticides - on reproductive systems in both humans and animal models. In women, the authors connect EDC exposure to a spectrum of disorders: infertility, irregular cycles, premature ovarian insufficiency, endometriosis, PCOS, and fibroids. The authors emphasize how exposure during sensitive life stages (e.g., gestation, puberty, and early adulthood) can trigger persistent and even transgenerational dysfunction.

 

For female veterans and survivors - particularly those exposed through military uniforms, water contamination, or agricultural chemicals—this study offers evidence that their chronic gynecologic and fertility issues are not just anecdotal but biologically grounded in chemical interference with the endocrine axis.

​

​

 

 

Carloni, M., Nasuti, C., Fedeli, D., & Gabbianelli, R. “Early Life Permethrin Exposure Induces Long-Term Brain Changes in Nurr1, NF-κB and Nrf2.” Brain Research 1515 (2013): 19–28.

https://doi.org/10.1016/j.brainres.2013.03.048.

​

This study confirmed that permethrin exposure in early development disrupts transcription of nuclear receptors and antioxidant defense genes. Reduced expression of Nurr1 and Nrf2 predisposes individuals to neuroinflammation and impaired gonadal regulation. The survivor’s reproductive decline and neurologic instability likely stem from similar pathways initiated by her early military exposures.

​

These findings reinforce the core narrative of Chapter 14: that the gynecological and breast disorders experienced by female veterans exposed to permethrin and DEET are not isolated events, but predictable outcomes of molecular injury - reproducible, measurable, and entirely preventable with exposure-aware diagnostics.

​

​

​

​

Sofia Macedo, Elisabete Teixeira, Tiago Bordeira Gaspar, Paula Boaventura, Mariana Alves Soares, Leandro Miranda-Alves, Paula Soares. “Endocrine-disrupting chemicals and endocrine neoplasia: A forty-year systematic review.” Environmental Research, Volume 218, 2023. 114869. ISSN 0013-9351. 

https://doi.org/10.1016/j.envres.2022.114869.

https://www.sciencedirect.com/science/article/pii/S001393512202196X

​

Abstract: Introduction

Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.

​

Aim

To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.

​

Methods

A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.

​

Results

Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43–67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).

​

Conclusions

The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.

​

Keywords: Endocrine disrupting chemicals; Cancer prevalence; Neoplasia prevalence; Human health; Environmental hazard

 

This 40-year systematic review evaluates 237 human studies investigating the association between EDC exposure and hormone-sensitive tumors - specifically cancers of the breast, prostate, thyroid, uterus, testis, and ovary. The authors highlight phthalates, pesticides, heavy metals, and particulate matter as the most tumorigenic, with thyroid and breast cancer showing the highest correlation with EDC exposure. Critically, it also points to the “cocktail effect” of multiple EDC exposures acting synergistically at even low doses.

 

For female survivors who have battled reproductive cancers or endocrine tumors, this paper strengthens the link between their diagnoses and long-term exposure to complex chemical mixtures - especially those like DDT, DEET, atrazine, and perfluorinated compounds used in military and civilian contexts alike.

 

 

 

 

Summary Insight

The gynecological and breast system disruptions observed in the survivor are not idiopathic, age-related, or stress-induced; they are biologically plausible outcomes of permethrin and DEET co-exposure under extreme environmental stress. This literature review affirms a mechanistic chain linking uniform-mediated dermal absorption to hormone receptor interference, ovarian atrophy, mammary epithelial mutation, and inherited epigenetic risk.

​

The studies presented do more than support the survivor's clinical history - they mirror it. From early menopause and PCOS to fibrocystic breast changes and transgenerational vulnerability, the toxicological evidence leaves little room for doubt. The survivor's exposures have left a molecular signature that transcends generations. BioSymphony's task is to make those signatures visible, actionable, and justiciable.

​

This review demands that gynecological conditions and breast disease in toxicant-exposed women be elevated from diagnostic blind spots to front-line indicators in exposure-aware care protocols. The literature doesn’t just support this claim. It compels it.