Sexuality–DES Research Highlights

 

My Academic Research Into Prenatal Hormonal Influences on Gender and Sexual Development in Men and Women, 1995 to 2020 (DES Research)

Scott P. Kerlin, PhD., M.S.

Overview: I have more than 25 years of interdisciplinary research into the effects of prenatal exposure to estrogenic and androgenic hormones on subsequent human behavioral development (including sexuality and gender identity), a field with extensive research investigation in the 1970s by Dr. June Reinisch, former director of the Kinsey Institute (see, for example, her 1984 journal article in Progress in Brain Research) and Dr. Dick Swaab of the Netherlands Institute for Neuroscience (see his co-authored 2010 article on Sexual Hormones and the Brain, published in the journal Pediatric Neuroendocrinology). 


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 and which led me to launch an online research network in 1999: DES-Sons International Research Network.

 

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 5  to 10 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 

As a verified DES Son, I have held long-standing interest in the 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 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. 


Literature Review: Human Health Effects of Diethylstilbestrol Exposure in Males and Females 

Here is a portion of the published research that I reviewed in my initial background investigation and continued assessments.  

General References 1939-2020


Psychosexual and Behavioral Developmental Effects, 1959-2019

Books on DES Legacy and Implications

There are several books devoted to the legacy of DES in humans. I especially recommend these texts:

Research into the possible inherited effects of prenatal DES exposure for third-generation “DES grandchildren” has also been published since 2000.  Examples:

DES Third-Generation Effects Literature, 2002-2019

 

Highlights and Timeline of My Initial Research Investigation, 1995-2006

  • 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. 
  • 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 1999-2004 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; (2) gender identity and sexual health issues and (3) psychological/mental health issues including anxiety and depression.  As of 2020, the DES Sons’ Network is still active.

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 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.
  • In 2002, I coauthored with Dr. Dana Beyer an article entitled “The DES Sons’ Online Discussion Network” for the Winter 2002 issue of the journal Transgender Tapestry
  • 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 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. My investigative research continued during 2005-06 at the University of British Columbia in Vancouver.
  • 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).
  • In 2003, I produced a thesis at UVic entitled “Hormones, Sexual Behavior, and Gender Identity in Human Development.”
  • 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 variance during adulthood?
  • 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 development.” His advice was of tremendous assistance in helping to develop an action plan for making my research more visible to an international research community.
  • 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, Deborah Rudacille published The Riddle of Gender with a chapter summarizing my ongoing 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.
  • In 2006, the Gender Identity Research and Education Society (GIRES) recognized prenatal DES exposure as a contributing factor in gender-related disorders in its comprehensive overview Atypical Gender Development–A Review.


2007 to the Present

The initial findings from my research, presented to international conference (International Behavioral Development Symposium in Minot, North Dakota) in 2005, provided the opportunity to further explore the validity of a hypothetical correlation between prenatal DES exposure in males and females and variations in core gender identity and sexual development across the lifespan. Meanwhile, the DES Sons Research Network and its companion DES-Trans Transgender Support Group have continued to be active into 2020.

For several years subsequently, the question of whether prenatal estrogenic hormone exposure in males can be directly linked to gender dysphoria, transexualism, transgenderism, intersex, and variations in sexual orientation has been further investigated by others.

Though no definitive conclusion regarding the role of prenatal DES exposure in shaping psychosexual development in males and females has yet been reached, there is now (2020) a much broader array of promising investigative studies devoted to this question. 25 years since beginning my own research investigation, I find this truly encouraging. 

Here are some representative examples of others’ investigations and findings.

Other Published Research Into Prenatal and Biological Influences on Sexual Orientation and Gender Identity: 

Recent Studies (2013 to 2020)

Foundational Studies (2000 to 2012)

2020: Newest published cohort study of prenatally DES-exposed males and females:

Gender Identity and Sexual Orientation Identity in Women and Men Prenatally Exposed to Diethylstilbestrol (2020), by Rebecca Troisi, et al., published in the Archives of Sexual Behavior.

My Initial Observations on this Publication:

(1) This study was based on a single-question demographic category identification  methodology in mailed follow-up surveys using the long-term DES Combined Cohort Study of DES Sons and DES Daughters, funded by the National Cancer Institute. The NCI-funded research has historically emphasized an effort to statistically measure trends in cancer prevalence in DES Sons, DES Daughers, and DES Mothers.  To the best of my knowledge, the Combined Cohorts are the only current population samples of DES Sons and DES Daughters in the U.S. that are still being monitored systematically.

(2) In the combined-cohort study, initial surveys were mailed in 1994 to approximately 1700 DES Sons and 4500 DES Daughters and subsequent surveys to this same population  approximately every five years between 1994 and 2016. The population in this study was from a single large fertility clinic (unidentified) in the U.S. 

(3) As with most research on DES Combined Cohorts, this study does not have a sophisticated foundational understanding of prenatal hormones and psychosexual development.  

(4) In measuring the survey respondents’ “sexual orientation”, data analysis was based on single questions in the 2016 surveys which asked respondents to check a box on “how do you identify: (a) gay or lesbian; (b) straight; or (c) other;” [sexual orientation].

(5) Though this study purports to measure “gender identity” of DES-exposed Sons and Daughters,  a standard question was asked on the questionnaire,  “Which of the following best represents how you currently think of yourself: “Woman”, “Man”, “Other”, and “Prefer not to respond.” This could easily have been inferred by most respondents as a standard “what sex are you?” kind of question. Indeed, more than 99% of respondents among both DES Daughters and DES Sons classified themselves as “female” and “male” respectively.

(6) Among DES Sons participating in these studies, the researchers report that DES Sons had a higher likelihood of reporting being either “gay” or “bisexual” than did DES Daughters. 

(7) The study reports that “very few individuals think of themselves as a ‘gender other than that assigned at birth.'” The authors confirm that gender identity is a complex construct, and may not be effectively assessed through the questionnaire format they utilized. 

In conclusion, I believe that this 2020 publication is not a reference standard on measuring the true scope of complex psychosexual effects of prenatal DES exposure in males and females, many of which are not easily measured from demographic data questionnaires.

To quote the authors of this study in their conclusion (page 453): “Although our study was large and has documented DES exposure status, it has limited power to assess associations with rare outcomes such as transgender identity. Despite limitations, these are unique data on a group of individuals exposed to high doses of synthetic estrogen during a particularly important development period.”

Observations: Implications of My Research Findings 

  • I have chosen to treat this study as primarily investigative in nature and not yet reaching definitive conclusions about the full scope of possible effects attributable to prenatal DES exposure. Further interviews and direct assessment of DES-exposed individuals are strongly recommended. 
  • In total, I estimate that 1000+ individuals have participated in the DES Sons network discussions during the period of 1999 through 2020. 
  • In my research interactions (through meetings, interviews, surveys) with the individuals who participated in the DES Sons network, it was not possible to independently verify that prenatal exposure to DES had definitely occurred, except in the cases when the individuals’ medical records were actually located. However, I utilized rigorous screening methods to verify likelihood of prenatal exposure before permitting DES Sons to participate. 
  • Verification of DES exposure status has always been a challenge, though many members were trained in ways of establishing verification through access to their medical records or through direct conversations with their parents or immediate family members. 
  • The initial findings in my surveys of individual DES-exposed persons born or raised as males (conducted during the period of 1999 through 2006) revealed a significant prevalence of hormonal disorders such as hypogonadism (testosterone deficiency), which is consistent with findings suggested in the early 2000s by the American Association of Clinical Endocrinologists (AACE).
  • In my own deep quantitative and qualitative research with DES sons over the period of 1999 to 2020, I learned that many of them described a history of suffering from gender dysphoria that is not easily measured by a simple question in a survey. 
  • The emergence of discussions of gender identity-related concerns among participants in the DES Sons network (late 1999 and onward through early 2000s during my initial investigation period) was not expected or predicted ahead of time. 
  • The prevalence of gender dysphoria among many participants in this study lends evidence to the finding of Ettner in Etiology of Gender Dysphoria (2020), who observes that “Early hormonal influences on the brain appear to account for different brain phenotypes and may ultimately provide answers to the origins of gender incongruence.(In L. Schecter, Gender Confirmation Surgery, (2020) pp. 21-28)
  • As noted above, there were relatively few reported instances of DES sons developing or experiencing cancer that was potentially linkable to their prenatal exposure. However, approximately 10 individuals reported a history of testicular cancer diagnosis and treatment.
  • Several individuals I encountered who had verified prenatal DES exposure reported congenital deformities of the male reproductive system including hypospadias, cryptorchidism, and epididymal (benign) cysts. 
  • Throughout my years of study of the health effects of DES Sons since my initial formation of the DES Sons International Research Network, it has become clear that males are typically reluctant to discuss their health challenges and concerns. This has made it a continual challenge for me as primary researcher when attempting to validate individual stories relative to likelihood of prenatal DES exposure.

Discussion 

  • Many of the issues raised within my study of DES-exposed males tended to go to  the heart of previous research investigations into factors that shape psychosexual development. The original motivation for my investigative study of DES-exposed males (1999) was not meant to establish or argue for a “causal link” between prenatal DES exposure and potential impact on the development of core gender identity, although I did have many questions stemming from early DES studies of psychosexual development such as Yalom et al, 1973. Nevertheless, in my early years of investigating the published DES literature stemming from the 1960s onward, it became apparent that other research scientists have also asked questions that go to the heart of the hormonal impact on human sexual development. 
  • Over the range of time in history since the earliest investigations (1960s) into the human health effects of prenatal DES exposure in males and in females, the scientific notions of hormonal influences over core gender identity have significantly evolved. 
  • In my extensive literature review into DES psychological effects, I encountered a major literature review completed in 2001 a published study by Michel, Mormont, and Legroes in the European Journal of Endocrinology, “A Psycho-endocrinological Overview of Transsexualism,” in which the authors suggested prenatal exposure to DES as a contributing factor in males gender-identity disorders and in some cases, transsexualism. 
  • At the heart of my study of DES sons and the nature of historical research into hormonal influences over the development of core gender identity in humans, I found it tremendously valuable to ground my findings in the studies of Dr. Milton Diamond. I was strongly influenced by his 2009 article in Hormones and Behavior, “Clinical Implications of the Organizational and Activational Effects of Hormones.
  • In developing my framework for further analysis of the gender identity issues raised by many members of my DES Sons network, I found it informative to consult references from the evolving body of literature associated with the fields of Transgender Health, as informed by participants in the World Professional Association for Transgender Health (WPATH). 
  • In my continuing investigation into the evolving research theories about gender identity formation, I have found the WPATH guidelines particularly beneficial in providing definitions of key constructs in transgender health. One contemporary reference that is of great assistance is the chapter on Language and Terminology in Transgender Health (2020) by Dr. Gail Knudson of the University of British Columbia Canada Faculty of Medicine, from the textbook Gender Confirmation Surgery. Knudson defines “gender dysphoria” this way:
    • Gender Dysphoria: Refers to discomfort or distress that is caused by a discrepancy between a person’s gender identity and that person’s sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics). Only some gender-noncomforming people experience gender dysphoria at some point in their lives.
  • I have found several key references that underscore the core aspects of prenatal hormonal influences on the development of gender dysphoria. For example, Capetillo-Ventura et al, in Gender Dysphoria: An Overview (2014), Medicina Universitaria state, 

Various authors conclude that the factors which affect gender during early development are prenatal hormones and the components that change these hormone levels (p.56).