DES and Human Health Effects: Emphasis on Gender and Sexuality

[Note: A full directory of DES-related research is available at this link: Diethylstilbestrol (DES): Multigenerational Research Trends 1939-2023]

My Continuing Academic Research Into Prenatal Hormonal Influences on Gender and Sexual Development in Men and Women

Scott P. Kerlin, PhD., MSc

[Paper presented to the December 2020 International Conference Beyond Genes: The Online Conference on Non-Genetic Inheritance in Human Disease. Accompanying video presentation is available here.]

Overview: I have more than 30 years of interdisciplinary research into the effects of prenatal exposure to estrogenic and androgenic hormones on human behavioral development (including sexuality and gender identity). This is a field with extensive research investigation since its origins in the 1970s by Dr. June Reinisch, former director of the Kinsey Institute. My continued research was inspired by the lifetime work of Dr. Milton Diamond at the University of Hawaii. Dr. Diamond was a major advocate for my ongoing research into the psychosexual effects of prenatal exposure to endocrine-disrupting hormones. 

Background of Existing Research on Prenatal Hormones and Psychosexual Development in Males and Females

Introduction

Historically, there has been a significant body of  literature on prenatal androgens and association with variations in gender and sexual development. Much of the existing published research on hormonal influences over gender identity development and the human brain focus only on impact of prenatal androgens and female development (for examples, see Berenbaum & Beltz, 2017, How Early Hormones Shape Gender Development, Hines, 2011, Annual Reviews on Gender Development and the Human Brain, and Hines, 2010, Sex-Related Variation in Human Behavior and the Brain from the journal Trends in Cognitive Sciences.)

There is far less long-term research on prenatal exposure to estrogens in males and psychosexual development (cite Yalom, Green and Fisk, 1973, Journal of the American Medical Association and Meyer-Bahlburg, 1978, published in the journal Pediatrics).  This is an area that I have researched in depth from the  1990s onward.

The Diethylstilbestrol (DES) Story 

DES, the abbreviation for “Diethylstilbestrol“, is a non-steroidal estrogenic drug  and sex hormone that was given to millions of women in the U.S. and other countries during the 1940s to 1970s (and beyond) for management of pregnancy. An estimated 3  to 6 million “DES daughters” and “DES Sons” were born in the U.S. and many more in Canada, Europe, and Australia. DES is classified as an endocrine disruptor because of its detrimental effects on the development of the endocrine system. 

A substantial array of adverse effects of DES has been documented in mothers and their offspring. The scope of reported effects has included cancer, physiological effects in daughters and sons, hormonal disorders, and psychiatric consequences. Additionally, several studies investigating the psychosexual effects of DES exposure in male and in females have been developed since 1959.

An extensive body of medical literature has been published about DES as early as 1939. The largest array of publications has been released since the early 1970s, when prenatal DES exposure in females was linked to a rare form of vaginal cancer. Here is an excellent, if somewhat dated research article from 2013:

• Exposure to Diethylstilbestrol During Sensitive Life Stages: A Legacy of Heritable Health Effects (November, 2013 full text), by Casey E. Reed and Suzanne E. Fenton, published in the journal Birth Defects Res C Embryo Today

DES has been extensively documented by the National Library of Medicine. For substantial reference on the biochemical makeup of DES and subsequent documentation of effects, see the National Library of Medicine’s Dictionary of Organic Compounds: DES directory. The summary entry for DES is the following:

Diethylstilbestrol is a synthetic, nonsteroidal form of estrogen. A well-known teratogen and carcinogen, diethylstilbestrol inhibits the hypothalamic-pituitary-gonadal axis, thereby blocking the testicular synthesis of testosterone, lowering plasma testosterone, and inducing a chemical castration.

History of My Research Investigation Into Human Health Effects of Prenatal DES Exposure Since 1995

As a verified DES Son and academic researcher, I have held long-standing interest in the full array of adverse effects of prenatal DES exposure in males as well as in females, which I began to investigate in 1995. 

When I first began to ask questions about the full scope of human effects, I learned that historically, DES-exposed females (i.e. “DES Daughters”) had a primary emphasis on the scope of research, particularly in the realm of cancer research. I became involved with the Montreal, Canada-based advocacy group DES Action Canada in 1997 as research specialist focusing on DES sons. 

When I first organized the DES Sons’ International Research Network online in 1999, my aim was to document the full range of reportable adverse effects in males, including testicular cancer, infertility, hormonal disorders such as hypogonadism, and behavioral developmental effects. It is important to note that compared with DES Daughters, there were relatively few published studies that investigated the full range of adverse health effects in males. 

Highlights and Timeline of My Initial Research Investigation

• In 1995, I began to investigate the historical published research on the adverse effects of prenatal exposure to diethylstilbestrol. I learned that in 1992, the U.S. National Toxicology Program’s Pub Chem database documented DES as having a variety of “health hazards.” These included causing “male impotence and transsexual changes”, along with “congenital malformation in the fetus.”
  
  
• In the mid 1990s I became an early adopter of using the Internet to conduct and develop investigative qualitative research. I have devoted many years to studying and developing the process of collecting qualitative data collection in online social communities. One article of more recent focus in this area is the article “Recommendations for Internet-Based Qualitative Health Research With Hard-to-Reach Populations”, by Michael Wilkerson, et al (2014), published in the journal Qualitative Health Research.
  
  
• In 1999, I founded the DES-Sons International Research Network, an online network intended to reach as broad a range of DES Sons as possible and to enable the sharing of personal experiences and insights as well as to discuss unanswered questions. At the time, DES Sons had very limited support from the mainstream DES Action network based in the U.S., but I was able to partner with DES Action Canada for stronger support and outreach.
  
  
• Between 1999 and 2004, I documented the health history of more than 500 DES sons who participated in discussions in the DES Sons International Research Network. I conducted extensive interviews with network members during these years in order to verify likelihood or confirmation of prenatal DES exposure and subsequent developmental history (physical, physiological, and psychological).
  
  
• A core aspect of my utilization of Internet discussion network format was through developing focused discussions and emerging themes that evolved using rigorous qualitative research methods. The DES Sons network was designed to create a virtual “safe space” of an epidemiological nature, for disclosure of issues that had never before been explored in depth. Through the trust that I created as a leader of group discussions, insights were developed by participating members that led identification of a constellation of physiological and psychological effects traceable to the prenatal DES exposure. 
  

A summary of my key findings from the 1999-2006 focus is available at Basic Statistics and Findings on DES Sons. The most frequently cited concerns among the study participants were (1) hormonal/endocrine health issues, especially hypogonadism; (2) gender identity and sexual health issues and (3) psychological/mental health issues including anxiety and depression.  

Study Statistics and Preliminary Findings

The initial period of my full qualitative online study spanned five years, from July 1999 to July 2004 but was extended to 2006 in order to gather additional interview data. What follows is a brief summary of the results based on feedback from more than 500 initial study participants.

Sample Size

By July 2004, a sample of approximately 500 males with confirmed (60% of total) or “strongly suspected” DES exposure (40% of total) participated in the DES Sons International Network research and provided a summary of major health, medical, and psychological issues they had encountered across the lifespan. Among the 60% of participants who indicated they had confirmed their exposure, the majority of confirmations came from the mother’s verification of having been given DES at some time during the pregnancy. The total number of study participants who have confirmed their exposure through direct access to their mothers’ medical records continues to be investigated.

Nations of Origin

Approximately 85% of network members were born in the U.S., while 5% each indicated they were born in Canada, Europe (chiefly UK) or Australia.

Core Health Concerns of DES Sons

Based on preliminary analysis of critical health issues reported by individual DES sons in the network, the three topics most frequently listed among the sample of 500 individuals with confirmed or suspected prenatal DES exposure are (a) gender identity concerns (at least 150 reports); (b) psychological/mental health issues, especially depression and anxiety disorders (at least 100 reports); and (c) hormonal/endocrine health issues (at least 75 reports).

Additional Reported Adverse Health Effects

Though identified less frequently in overall health reports provided by study participants, several participants listed histories of infertility, reproductive tract abnormalities (including reports of ambiguous or underdeveloped genitalia), epididymal cysts, cryptorchidism, hypospadias, gynecomastia, and erectile dysfunction. Statistics on the full extent of reporting of these concerns are still undergoing analysis.

Prevalence of Male-to-Female Transsexual, Transgender, and Intersex Individuals

More than 150 network members with “confirmed” or “strongly suspected” prenatal DES exposure identified as either “transsexual, pre- or postoperative,” (90 members), “transgender” (48 members), “gender dysphoric” (17 members), or “intersex” (3 members). These statistics are taken from selfreport terms provided by individual participants in their health histories.

Low Cancer Prevalence

Only 7 individuals with confirmed or “strongly suspected” prenatal DES exposure have reported experiencing some form of cancer. Most were testicular cancer survivors.

Initial Research Advancements/Conclusions – 1999-2006

• Among the most significant findings from this qualitative research study is the high prevalence of individuals with confirmed or strongly suspected prenatal DES exposure who self-identify as male-to-female transsexual or transgender, and individuals who have reported experiencing difficulties with gender dysphoria.

In my initial study begun in 1999, more than 150 individuals with confirmed or suspected prenatal DES exposure reported moderate to severe feelings of gender dysphoria across the lifespan. For most, these feelings had apparently been present since early childhood. The prevalence of a significant number of self-identified male-to-female transsexuals and transgender individuals as well as some individuals who identify as intersex, androgynous, gay or bisexual males has inspired fresh investigation of historic theories about a possible biological/endocrine basis for psychosexual development in humans, including sexual orientation, core gender identity, and sexual identity (Benjamin, 1973; Cohen-Kettenis and Gooren, 1999; Diamond, 1965, 1996; Michel et al, 2001; Swaab, 2004).

• Mental health and psychiatric issues (including depression and anxiety disorders) were relatively significant among the population of DES sons participating in this research.

This study’s findings provide fresh evidence of psychiatric disturbances among individuals exposed to DES. It is hopeful that future research on human health effects of exposure to endocrine disrupting chemicals (i.e., assessing neurotoxicity) can include psychiatric disturbances such as major depression, anxiety disorders, eating disorders, and psychoses as potential endpoints for analysis of the long-term effects from prenatal exposure. Additional questions may be explored as to whether psychiatric conditions such as increased depression and/or anxiety disorders in DES sons have a foundation in primary endocrine system disorders.

• Endocrine system disorders such as hypogonadotropic hypogonadism in DES sons have been among the more common reported adverse health effects in this research study. This is a condition that I personally have been diagnosed and treated with since 2000. 

Although the prevalence of endocrine system disorders among DES sons has not been discussed in any of the existing published epidemiological research on DES-exposed populations, both the Endocrine Society and the American Association of Clinical Endocrinology (2002) have recognized prenatal DES exposure as a risk factor for endocrine disorders including hypogonadism. This study confirms that this issue needs further attention in future studies of DES sons.

• Relative infrequency of reported cancer among the DES sons in this research is consistent with most existing long-term studies demonstrating limited cancer prevalence in males with prenatal DES exposure.

While the rate of total cancer occurrence among members of the DES Sons International Network is uncertain, numerous efforts have been made to generate discussion about cancer risks and in particular, to encourage dialogue regarding testicular cancer experiences. Approximately seven members of the network between the study years of 1999 and 2004 indicated some past or present experience with testicular cancer. It appears that overall cancer outcomes among network members have been low, a finding consistent with research by Strohsnitter et al. (2001).

Based on the findings in this study, research into the human health effects of exposure to endocrine disrupting chemicals needs to focus on additional behavioral toxic endpoints besides those historically investigated.

Discussion on the Emergence of Gender-Related Concerns Among DES Network Members

• Within the first few months of my formation of the DES Sons’ network, more than 250 individuals expressed interest in joining the private discussion network. Before admitting members,  I interviewed and surveyed each applicant to determine (1) likelihood of confirmed prenatal DES exposure; (2) health history and evidence of any documented physiological or mental health difficulties.
  
  
• Between the years of 1999 and 2003, I conducted a series of surveys of members in order to determine which issues were most prevalent in areas of concern. My own investigation revealed patterns and outcomes in many DES sons that paralleled what was documented in published research. Documentation of my full research and data collection process was retained within the DES Sons’ research network archives that I maintained from 1999 to 2020.
  
  
• What I learned very soon after launching the original DES Sons’ network email discussion list on Yahoo (DES-Sons) in 1999, was that a significant number of new members who introduced themselves to the group and/or to me in private communications described a history of gender dysphoria and other gender and sexuality related issues.
  
  
• During conversations among network participants, several members reported a variety of issues and concerns related to gender identity, gender dysphoria, and transgenderism. Because of the sensitive nature of this topic, it took several months for members to self-disclose their history of gender-related concerns. These were provided to me in most cases privately.
  
  
• In 2001 I formed a separate discussion list called DES-Trans Support Group. There was a substantial amount of discussion activity on DES-Trans that truly underscored for me the importance of further exploring a possible link between prenatal DES exposure and psychosexual issues.
  
  
• Through my extensive experience with conducting qualitative research in an online environment, I was able to develop an environment of trust and respect for all members, allowing me to ask questions that further probed the nature and history of gender dysphoria and transgender identity among DES Trans members. The evolution of this topic is reported on DES Sons and the Significance of Gender Identity.
  
  
• During the next several years, discussions on the DES-Sons tended to focus on cancer concerns and other physiological effects in exposed males, while DES-Trans tended to focus on psychosexuality and gender identity.
  
  
• In fall of 2002 I was interviewed by a member of the DES-Trans support group for a program she produced for radio station KBOO in Portland, Oregon, which was entitled “Under Our Skins: The Hidden Story About DES and Transgenderism.”
  
  
• In 2002, I was interviewed on the program GenderTalk Radio regarding my first discoveries of a possible link to transsexualism resulting from hormonal disturbances in males at birth. I coauthored with Dr. Dana Beyer an article entitled “The DES Sons’ Online Discussion Network” for the Winter 2002 issue of the journal Transgender TapestryDeveloping an Academic Framework for Investigating the Effects of DES 
  
  
• In the years 2002-2004 I participated as a Visiting Research Scholar in Psychology at the University of Victoria (Canada). During this period I conducted a scholarly literature investigation about hormones and human sexual behaviour, focused on the biological and psychological frames of reference for conducting scientific studies of human sexual development.
  
  
• During 2003-5, I received invaluable support and consultation from the world-renowned sexologist Dr. Milton Diamond, who indicated through email and telephone conversations that he had “long suspected that prenatal DES exposure had significant developmental effects on gender and sexuality.” His advice was of tremendous assistance in helping to develop an action plan for making my research more visible to an international research community. During this period we discussed several published studies that proved to be highly influential over my evolving thesis.
  
  
• One particular study that Dr. Diamond recommended for my ongoing work is Does Prenatal Exposure to Diethylstilbestrol (DES) have Psychiatric Consequences? (2000), by Helene Verdoux, published in the journal Annales Medico-Psychologiques, Vol 158 (2), p. 105-117. This article abstract is:>> Diethylstilbestrol (DES) has been widely used around the word in pregnancy care until the discovery in the early 1970s of the teratogenic and carcinogenic effects of this drug. The genital and obstetrical iatrogenic effects of the intrauterine exposure to DES are now well established. However, the potential impact of the DES and related xenoestrogen on the foetal neurodevelopment are poorly known. It has been suggested that prenatal DES exposure may modify the cerebral lateralisation. A more speculative issue with regard to the possible neurodevelopmental consequences of DES exposure is the possible impact on gender-identity and gender-related behavior.  Prenatal DES exposure may be also a risk factor for psychiatric disorder in adulthood. This increased liability can not be totally explained by the genital and reproductive consequences of DES exposure, since it can also be found before the appearance of such complications and/or in subjects unaware of their exposure to DES, and also exists in DES-exposed sons who do not present with somaticcomplications. Most previous studies have assessed the links between perinatal DES exposure and increased risk of depression. A few reports also suggest that subjects exposed to DES may be at greater risk of eating or psychotic disorders. Further research on the neurodevelopmental consequences of xenoestrogen exposure is required from an aetiological perspective, but also from a preventive point of view.
  
  
• In March 2003, I participated in a transcribed telephone interview with DES researcher Dr. John McLachlan on the topic of feminization of males exposed to DES in-utero during the DES Update of the Centers for Disease Control (CDC). Dr. McLachlan was also a strong supporter of my ongoing research investigation.
  
  
• In 2003, I identified several historical medical research studies of transsexual patients (male to female) who were treated with DES, a practice that apparently was quite common in gender transition clinics prior to 1980. One example of such a study is “Mortality and Morbidity in Transsexual Patients with Cross-Gender Hormone Treatment“, by H. Asscheman, L.J.G. Gooren, and P.L.E. Eklund.
  
  
• Formulating a DES Research Hypothesis: In 2003, following extensive interviewing and surveying of members of the DES Sons and DES Trans groups, I decided to pose a fomal research hypothesis: If DES was at one time considered an effective estrogen for supporting gender transition for male-to-female transsexuals, could prenatal exposure of the male fetus to DES also be implicated in subsequent gender dysphoria and gender variance during adulthood? 
  
  
• In 2003, I produced a graduate thesis at the University of Victoria entitled “Hormones, Sexual Behavior, and Gender Identity in Human Development.” One of the advising faculty for my thesis was Dr. Aaron Devor, professor of sociology at the University of Victoria and developer of The Transgender Archives. My investigative research continued during 2005-06 at the University of British Columbia in Vancouver with guidance from Dr. Gail Knudson of the UBC Department of Psychiatry, an active leader of the World Professional Association for Transgender Health (WPATH). Knudson verified her long-standing belief that prenatal DES exposure might have significant impact on psychosexual development.
  
  
• In 2004, at the invitation of DES researcher Dr. John McLachlan at Tulane University, I presented preliminary findings from 5 years of research into prenatal exposure to the estrogenic drug DES (diethylstilbestrol) to the annual E.Hormone academic conference at Tulane University. A slideshow of this presentation is available, entitled “The Presence of Gender Dysphoria, Transsexualism, and Disorders of Sexual Differentiation in Males Prenatally Exposed to Diethylstilbestrol: Initial Evidence of a 5-Year Study.”
  
  
• In 2004, I served as a member of the faculty research committee for Christine Johnson, a master’s degree recipient at the Evergreen State University in Olympia, Washington. Johnson is a DES-Son who transitioned to female in her 20s. Johnson’s thesis is entitled Transsexualism: An Unacknowledged Endpoint of Developmental Endocrine Disruption?  The full 212-page thesis is available here.
  
  
• In 2005 I presented an invited research paper Prenatal Diethylstilbestrol Exposure and Gender-Related Disorders: Results from a 5-Year Study to the International Behavioral Development Symposium which was consulted and supported by renowned sexologist Dr. Milton Diamond of the University of Hawaii School of Medicine and Dr. John McLachlan of Tulane University School of Medicine. I also participated in a radio interview on my research for KWMR Radio.
  
  
• An article which highlights my research was published in 2006 by Ernie Hood in Environmental Health Perspectives, “Are EDCs Blurring Issues of Gender?” 
  
  
• In 2006, the Gender Identity Research and Education Society (GIRES) of the UK recognized prenatal DES exposure as a contributing factor in gender-related disorders in its comprehensive overview Atypical Gender Development–A Review.
  
  
• In 2006, Deborah Rudacille, a science writer and researcher at Johns Hopkins University published the book The Riddle of Gender with a chapter interviewing me and summarizing my ongoing DES research. The chapter is titled “The Fear of a Pink Planet”. Several members of the DES Sons network, along with Dr. Milton Diamond, were interviewed for her book.Among the summary comments provided by Rudacille is the following (p. 255): “Kerlin and (co-DES Sons researcher) Beyer are convinced that the DES Sons’ network has broken the seal on the conspiracy of silence about the effects of DES exposure on sons, particularly its association with gender identity disorder in males. Not a single DES cohort study has explored this question. ‘It seems that the focus of any ongoing ‘cohort’ tracking for sons is to look for signs of cancer risk. Other health issues just don’t seem to be included…’, Scott Kerlin told me during a series of email and telephone conversations during 2002 and 2003. All current DES research is based on the DES Combined Cohort Studies (DCCS)–approximately 5000 women exposed to DES during pregnancy, four thousand unexposed (control) mothers; five thousand exposed and twenty-five hundred unexposed daughters; and two-thousand exposed and two-thousand unexposed sons. According to the U.S. Centers for Disease Control (CDC), ‘the goal of the DCCS is to determine whether the health risk of cancer as a result of being exposed to DES is increased as a result of exposure to DES. Other health outcomes, such as infertility and pregnancy outcomes are also being investigated through DCCS.’  It goes without saying, Kerlin and Beyer note,   that there is no mention of gender variance in these studies. ‘Those studies are just not looking at the question of gender variance or anything remotely connected to it.”
  
  
  Continuing Research, 2006-2023
  
  As is the nature of qualitative research, I have continued to interview new and continuing members of the DES-Sons and DES-Trans groups throughout the active cycles of their group discussions, which continued into 2018, and into 2023 with individual members of the DES Sons International Research Network. Key highlights of my discussions and findings will be presented during May and June 2023.
  
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  Note: Direct access to the full-text edition of this paper is available here.