DES and Endocrine Disruptors: Multiple Generations Research Trends 1990-2025

October 2025 Update

Scott Kerlin, Ph.D.
DES International Research Network

Overview

Since 1990, there has been a significant range of published research articles that recognize adverse effects of diethylstilbestrol (DES) in children born to mothers and fathers who were prenatally exposed to DES (i.e. third-generation “DES grandchildren”), as well as extensive studies of the epigenetic effects of endocrine disrupting chemicals.

Studies of DES impact on multiple generations have been substantially strengthened by the continually expanding body of literature emphasizing the human health effects of in utero exposure to endocrine-disrupting chemicals (EDCs) (Pan, 2024; Lite, 2022; Montjean, et al., 2022; Soyer-Goybillard, et al., 2021; Yim, et al., 2021; Rattan & Jodi A. Flaws, 2019; Walker & Gore, 2011). This section will continue to evolve as more related endocrine disruptors and epigenetics research citing DES is identified.

Frequently Listed Effects for Third Generation “DES Grandchildren”

* Increased risk for neurodevelopmental effects, particularly ADHD
* Increased risk for autism spectrum disorders (ASD)
* Increased risk for psychiatric disorders including: schizophrenia, bipolar disorder, behavioral disorders, eating disorders, obsessive-compulsive disorders, violence and addictions, major depression, gender dysphoria
* Increased risk in DES granddaughters of irregular menses and amenorrhea
* Increased risk of genital anomalies (particularly hypospadias and cryptorchidism) in DES grandsons
* Harmful effects on fertility and reproductive development in DES granddaughters
* Increased risk of endometriosis in DES granddaughters
* Increased risk of preterm delivery and possibility of ectopic pregnancy in DES granddaughters
* Cancer risk has not yet been conclusively identified in third-generation females or males
* MRKH Syndrome (congenital aplasia of the uterus and the upper two-thirds of the vagina)

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Journal References 1990-2025

2020-2025

• {NEW} Prenatal Exposure to Diethylstilbestrol has Multigenerational Effects on Folliculogenesis (2025), by Rachael E. Rogers, et al., published in Scientific Reports
  
  
• {NEW} In utero exposure to synthetic sex hormones and their multigenerational impact on neurodevelopmental disorders: Endocrine disruptors as neuroendocrine disruptors (2025), by Marie-Odile Soyer-Gobillard , Laura Gaspari , Charles Sultan, published in Journal of the Neurosciences (full-text)
  
  
• {NEW} The Invisible Influence: Can Endocrine Disruptors Reshape Behaviors Across Generations? (2025), by Antonella Damiano, et al., published in the journal Stresses (full-text)
  
  
• {NEW} Benign and Malignant Outcomes in the Offspring of Females Exposed In Utero to Diethylstilbestrol (DES): An Update from the NCI Third Generation Study (2024), by Linda Titus, et al., published in the journal Cancers (full-text)
  
  
• {NEW} The Adverse Role of Endocrine Disrupting Chemicals in the Reproductive System (2024), by Jing Pan, et al., published in the journal Frontiers in Endocrinology (full-text)
  
  
• {NEW} Observational Methods for Human Studies of Transgenerational Effects (2024), by Rebecca Richards-Steed, et al., published in the journal Epigenetics
  
  
• {NEW} The developmental origins of health and disease and intergenerational inheritance: a scoping review of multigenerational cohort studies (2024), by Jie Tan, et al., published in Journal of Developmental Origins of Health and Disease
  
  
• {NEW} Genome-wide methylation analysis in patients with proximal hypospadias – a pilot study and review of the literature (2024), by Yolande van Bever, et al., published in the journal Epigenetics (abstract)
  
  
• {NEW} Advancements in Hypospadias Management: Trends, Techniques, Training, and Patient-Centric Outcomes (2024), by Vinaya Bhatia, et al., published in Turkish Journal of Urology (abstract)
  
  
• Birth Outcomes in DES Children and Grandchildren: A Multigenerational National Cohort Study on Informative Families (2023), by Laura Gaspari, et. al, published in the International Journal of Environmental Research and Public Health (full-text)
  
  
• Effects of Prenatal Exposure to Synthetic Sex Hormones on Neurodevelopment: A Biological Mechanism (2023), by Marie Odile Soyer-Gorbillard, et al., published in the journal Frontiers in Molecular Neuroscience (full-text)
  
  
• Prenatal Exposure to Diethylstilbestrol has Long-Lasting, Transgenerational Impacts on Fertility and Reproductive Development (July 2023), by Rachael E. Rogers, et al., published in the journal Toxicological Sciences (full-text)
  
  
• A Scoping Review of Multigenerational Impacts of Grandparental Exposures on Mental Health in Grandchildren (2023), by Jingyuan Xiao, et al., published in the journal Current Environmental Health Reports (full-text)
  
  
• Role of Epigenetics in the Etiology of Hypospadias through Penile Foreskin DNA Methylation Alterations (2023), by Martin Kaefer, et al., published in the journal Scientific Reports (full-text)
  
  
• Like Mother, Like Daughter, Like Granddaughter… Transgenerational Ignorance Engendered by a Defective Reproductive Health Technology (2022), by Emmanuelle Fillion & Didier Torny, published in the journal Reproductive Medicine & Society Online
  
  
• Exposure to Distilbène® in utero: Transgenerational Effects (2022), by Sylvie Epelboin, Michel Tournaire, & Emmanuel Devouche, published in the French journal Reproductive Medicine (Médecine de la Reproduction) (Abstract only)
  
  
• Diethylstilbestrol and Autism (2022), by by Marie Odile Soyer-Gorbillard, Laura Gaspari, Philippe Courtet, and Charles Sultan, published in the journal Frontiers in Endocrinology (full-text)
  
  
• In utero Exposure to Endocrine-disrupting Chemicals, Maternal Factors and Alterations in the Epigenetic Landscape Underlying Later-life Health Effects (2022), by Chrysty Lite, et al., published in the journal Environmental Toxicology and Pharmacology (abstract only)
  
  
• Prenatal diethylstilbestrol exposure: Transgenerational transmission of adverse effects (2022), by Sylvie Epelboin, Michel Tournaire and Emmanuel Devouche, published in Médecine de la Reproduction
  
  
• Impact of Endocrine Disruptors upon Non-Genetic Inheritance (2022), by Debbie Montjean, et al., published in the International Journal of Molecular Sciences (full-text)
  
  
• Epidemiology of Hypospadias (2022), by Loes F. M. van der Zanden, et al., published in the textbook Hypospadias Surgery (Ahmed T. Hadidi, ed.)
  
  
• High Incidence of Mayer-Rokitansky-Küster-Hauser Syndrome in Third-Generation DES Women (2022), by Daniel Guerrier, et al., published in the journal Therapies (abstract)
  
  
• Prenatal Exposure to Diethylstilbestrol and Multigenerational Psychiatric Disorders: An Informative Family (2021), by Marie-Odile Soyer-Gobillard, et. al, published in the International Journal of Environmental Research and Public Health (full-text)
  
  
• Are the Effects of DES Over? A Tragic Lesson from the Past (2021) by Pilar Zamora-Leon, published in the International Journal of Environmental Research and Public Health (f-t)
  
  
• Pregnancy Endocrine Disruption and Obesity-related Outcomes in the Third Generation (2021), by G. Yim, A. Roberts, and M. Weisskopf, produced by the journal Environmental Health Perspectives (Abstract only)
  
  
• Consequences of in utero Exposure to Synthetic Estrogens and Progestens for Children and Grandchildren (2021), by Marie Odile Soyer Goybillard, Laura Gaspari, and Charles Sultan, published in the International Journal of Clinical Studies & Medical Case Reports  (full-text)
  
  
• Grandmothers’ Endocrine Disruption during Pregnancy, Low Birth weight, and Preterm Birth in Third Generation (2021), by Gyeyoon Yim, et al, published in the International Journal of Epidemiology (full-text)
  
  
• Chapter Five – Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models (2021), by Mary Jo Laws, et al., published in Advances in Pharmacology (abstract)
  
  
• Endocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives (2021), by Deidre M. Mattiske & Andrew J. Pask, published in Current Research in Toxicology (abstract)
  
  
• Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics (2021), by Lucia Migliore, et al., published in the journal Biomedicines (full-text)
  
  
• Diethylstilbestrol Exposure During Pregnancy with Primary Clear Cell Carcinoma of the Cervix in an 8-year Old Granddaughter: A Multigenerational Effect of Endocrine Disruptors? (2021), by Laura Gaspari, et. al, published in the journal Human Reproduction
  
  
• The Heritable Legacy of Diethylstilbestrol: A Bellwether for Endocrine Disruption in Humans (2021), by Suzanne Robotti, published in the journal Biology of Reproduction
  
  
• Evidence of Intergenerational Transmission of Diethylstilbestrol Health Effects: Hindsight and Insight (2021), by Linda Titus, published in the journal Biology of Reproduction (abstract only)
  
  
• Multigenerational Endometriosis: Consequence of Fetal Exposure to Diethylstilbestrol? (2021) by Laura Gaspari, et. al, published in the journal Environmental Health (full-text)
  
  
• The Prenatal Hormone Milieu in Autism Spectrum Disorder (2021), by Whitney Worsham, et. al., published in Frontiers in Psychiatry (full-text)
  
  
• Chapter Three – Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs), and the brain (2021), by Madeline Streifer & Andrea C. Gore, published in Advances in Pharmacology
  
  
• “Idiopathic” Partial Androgen Insensitivity Syndrome in 11 Grandsons of Women Treated by Diethylstilbestrol During Gestation: A Multigenerational Impact of Endocrine Disruptor Contamination? (2020), by L. Gaspari, et. al, published in the Journal of Endocrinological Investigation (abstract only)
  
  
• Genital Tract and Reproductive Characteristics in Daughters of Women and Men Prenatally Exposed to Diethylstilbestrol (DES) (2020), by Anne Wautier, et. al, published in the French journal Therapies (Abstract only)
  
  
• Oestrogenic Endocrine Disruptors in the Placenta and the Fetus (2020), by Zi-Run Tang, et al., published in the International Journal of Molecular Sciences (full-text)
  
  
• Evidence for Germline Non-genetic Inheritance of Human Phenotypes and Diseases (2020), by Liana Senaldi & Matthew Smith-Raska, published in the journal Clinical Epigenetics (full-text)
  
  
• Pregnancy Endocrine Disruption and Obesity-Related Outcomes in the Third Generation (2020), by G. Yim, A. Roberts, & M. Weisskopf, published in the journal Environmental Health Perspectives (Abstract only)
  
  
• Methodological Issues in Population-Based Studies of Multigenerational Associations (2020), by Glenn McGee, et. al, published in the American Journal of Epidemiology (full-text)
  
  
• Mini-review: Epigenetic Mechanisms that Promote Transgenerational Actions of Endocrine Disrupting Chemicals: Applications to Behavioral Neuroendocrinology (2020), by Mariangela Martini, et al., published in the journal Hormones & Behavior (full-text)
  
  
  2012-2019
  
  
• Reproductive and Hormone-Related Outcomes in Women whose Mothers were Exposed in utero to Diethylstilbestrol (DES): A Report from the U.S. National Cancer Institute DES Third Generation Study (2019), by Linda Titus, et. al, published in the journal Reproductive Toxicology (full-text)
  
  
• The Epigenetic Impacts of Endocrine Disruptors on Female Reproduction Across Generations (2019), by Saniya Rattan & Jodi A. Flaws, published in the journal Biology of Reproduction (full-text)
  
  
• Prenatal Diethylstilbestrol Exposure and Cancer Risk in Women (2019), by Rebecca Troisi, et. al, published in the journal Environmental and Molecular Mutagenesis (abstract)
  
  
• Pregnancy Drugs, Fetal Germline Epigenome, & Risks for Next-Generation Pathology: A Call to Action (2019), published in the journal Environmental and Molecular Mutagenesis
  
  
• Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification (2019), by Michele A. La Merrill, et al., published in Nature Reviews: Endocrinology
  
  
• Association of Exposure to Diethylstilbestrol During Pregnancy with Multigenerational Neurodevelopmental Deficits (2018), by Marianthi-Anna Kioumourtzoglou, et. al, published in JAMA Pediatrics (full-text)
  
  
• Diethylstilbestrol Exposure in Pregnancy Linked to Multigenerational Neurodevelopmental Deficits (2018), by Karen Rosenberg, published in the American Journal of Nursing (Abstract only)
  
  
• Birth Defects in Children of Men Exposed in utero to Diethylstilbestrol (DES) (2018), by Michael Tournaire, et. al, published in the French journal Therapies (f-t)
  
  
• Congenital Abnormalities of the Male Reproductive System and Risk of Autism Spectrum Disorders (2018), by Ran S Rotem, et al, published in The American Journal of Epidemiology
  
  
• Evidence for Link Between Mental Disorders and in Utero Exposure to Synthetic Hormones: A Long and Crucial History (2018), by Marie-Odile Soyer-Gobillard, Laura Gaspari and Charles Sultan, published in the book Psychopathology – An International and Interdisciplinary Perspective (ed: Robert Woolfolk, et al.)
  
  
• Grandmaternal Diethylstilbestrol and Attention-Deficit/Hyperactivity in Children –Reply (2018), by Marianthi-Anna Kioumourtzoglou & Marc G. Weisskopf, published in JAMA Pediatrics (abstract only)
  
  
• Pharmacologic and Environmental Endocrine Disruptors in the Pathogenesis of Hypospadias: a Review (2018), by Rajiv Raghavan, et al., published in the journal Current Environmental Health Reports (full-text)
  
  
• Current Perspective of Diethylstilbestrol (DES) Exposure in Mothers and Offspring (2017), by Taher Al Jishi & Consolato Sergi, published in the journal Reproductive Toxicology (full-text)
  
  
• Endocrine Disruptors and Obesity (2017), by Philippa D. Darbre, published in Current Obesity Reports (full-text)
  
  
• Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders (2017), by Shuk-Mei Ho, et al., published in the journal Reproductive Toxicology (full-text)
  
  
• Adverse Health Effects in Children of Women Exposed in utero to Diethylstilbestrol (DES) (2016), by Michael Tournaire, et. al, published in the French journal Therapies (f-t)
  
  
• Diethylstilbestrol (DES): Also Harms the Third Generation (2016), published in the French journal Prescrire International (abstract only)
  
  
• DES Exposure and Third Generation Attention Deficit/Hyperactivity Disorder (2016), by Marianthi-Anna Kioumourtzoglou, et. al, published in the journal Environmental Health Perspectives (full-text)
  
  
• Fertile ground: human endometrial programming and lessons in health and disease (2016), by Jemma Evans, et al., published in Nature Reviews: Endocrinology (full-text)
  
  
• Association Between Fetal DES-exposure and Psychiatric Disorders in Adolescence/adulthood: Evidence from a French Cohort of 1002 Prenatally Exposed Children (2015), by Marie-Odile Soyer-Gobillard, et al., published in the journal Gynecological Endocrinology (full-text)
  
  
• ** EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals (2014), by AC Gore, et al., published in Endocrine Reviews
  
  
• The History of Diethylstilbestrol told to Grandchildren–the Transgenerational Effect (2015), by Patrick Fénichel, Françoise Brucker-Davis, & Nicolas Chevalier, published in the journal Annales d’Endocrinologie (abstract only)
  
  
• Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility (2014), by Eric E Nilsson, published in Translational Research
  
  
• Exposure to Diethylstilbestrol during Sensitive Life Stages: A Legacy of Heritable Health Effects (2013), by Casey E. Reed & Suzanne E. Fenton, published in the journal Birth Defects Res C Embyo Today (full-text)
  
  1990-2011
  
  
• Transgenerational Neuroendocrine Disruption of Reproduction (2011), by Deena M. Walker and Andrea C. Gore, published in the journal Nature Reviews Endocrinology (full-text)
  
  
• Prevalence of Hypospadias in Grandsons of Women Exposed to Diethylstilbestrol during Pregnancy: A Multigenerational National Cohort Study (2011), by Nicolas Kalfa, et. al, published in the journal Fertility and Sterility (full-text)
  
  
• Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life (2011), by Retha Newbold, published in the American Journal of Clinical Nutrition (full-text)
  
  
• Endocrine Disrupters: A Review of Some Sources, Effects, and Mechanisms of Actions on Behaviour and Neuroendocrine Systems (2011), by C. Frye, et al., published in Journal of Neuroendocrinology (abstract)
  
  
• Birth Defects in the Sons and Daughters of Women who were Exposed in utero to Diethylstilbestrol (DES) (2010), by Linda Titus-Ernstoff, et. al, published in the International Journal of Andrology
  
  
• In Utero Exposure to Diethylstilbestrol (DES) or Bisphenol-A (BPA) Increases EZH2 Expression in the Mammary Gland: An Epigenetic Mechanism Linking Endocrine Disruptors to Breast Cancer (2010), by Leo F. Doherty, et al., published in Hormones and Cancer (full-text)
  
  
• Epigenetic inheritance in mammals: Evidence for the impact of adverse environmental effects (2010), by Tamara B. Franklin & Isabelle M. Mansuy, published in Neurobiology of Disease
  
  
• Long-term effects of environmental endocrine disruptors on reproductive physiology and behavior (2009), by Heather B. Partisaul & Heather B. Adewale, published in Frontiers in Behavioral Neuroscience (abstract)
  
  
• Offspring of Women Exposed in utero to Diethylstilbestrol (DES): A Preliminary Report of Benign and Malignant Pathology in the Third Generation (2008), by Linda Titus-Ernstoff, et. al, published in the journal Epidemiology (abstract only)
  
  
• Esophageal Atresia and Tracheoesophageal Fistula in Children of Women Exposed to Diethylstilbestrol in utero (2007), published in the American Journal of Obstetrics and Gynecology (abstract only)
  
  
• Adverse Effects of the Model Environmental Estrogen Diethylstilbestrol are Transmitted to Subsequent Generations (2006), by Retha R. Newbold, Elizabeth Padilla-Banks, & Wendy N. Jefferson, published in the journal Endocrinology (f-t)
  
  
• Hypospadias: A Transgenerational Effect of Diethylstilbestrol? (2006), by M. M. Brouwers, et. al, published in the journal Human Reproduction (full-text)
  
  
• Menstrual and Reproductive Characteristics of Women whose Mothers were Exposed in utero to Diethylstilbestrol (DES) (2006), by Linda Titus-Ernstoff, et. al, published in the International Journal of Epidemiology (full-text)
  
  
• Pregnant “DES Daughters” and their Offspring (2005), by Tal Schechter, Yaron Finkelstein, and Gideon Koren, published in Canadian Family Physician (full-text)
  
  
• Lessons learned from perinatal exposure to diethylstilbestrol (2004), by Retha R. Newbold, published in the journal Toxicology and Applied Pharmacology
  
  
• Ovarian Carcinoma in an Adolescent With Transgenerational Exposure to Diethylstilbestrol (2003), by Julie Blatt, et al., published in the Journal of Pediatric Hematology/Oncology
  
  
• Limb Reduction Deficits in the First Generation and Deafness in the Second Generation of Intrauterine-exposed Fetuses to Diethylstilbestrol (2003), by C. Stoll, Y. Alembik, & B. Dott, published in the journal Annales de Génétique
  
  
• Spontaneous Rupture of a First-trimester Gravid Uterus in a Woman Exposed to Diethylstilbestrol in utero: A Case Report. (2003), by Porcu G, et al., published in the Journal of Reproductive Medicine
  
  
• Hypospadias in Sons of Women Exposed to Diethylstilbestrol in utero: A Cohort Study (2002), by H. Klip, et. al, published in the journal Lancet (full-text)
  
  
• Findings in Female Offspring of Women Exposed in utero to Diethylstilbestrol (2002), by Raymond H Kaufman & Ervin Adam, published in the journal Obstetrics & Gynecology
  
  
• Continued Follow-up of Pregnancy Outcomes in Diethylstilbestrol-exposed Offspring (2000), by Raymond Kauffman, et al., published in the journal Obstetrics & Gynecology
  
  
• Diethylstilbestrol, Teratogenesis, and Carcinogenesis: Medical/legal Implications of its Long-term Sequelae, including Third Generation Effects (1990), by Henry T. Lynch, et. al, published in the International Journal of Risk and Safety in Medicine (abstract only)