Transsexualism : An Unacknowledged Endpoint of Developmental Endocrine Disruption?

Thesis for the Master of Environmental Studies Degree, Christine Johnson, 2004

Johnson is interviewed in Deborah Rudacille’s book The Riddle of Gender. She was born a DES son but transitioned to female (m to f) in her 20s. Scott Kerlin served on her Master’s degree thesis committee at Evergreen State University in Washington and this thesis contained extensive evidence of prenatal exposure to DES, DDT, PCBs, and other endocrine disrupting substances on gender identity and gender development.

Abstracts

In recent years, evidence has accumulated demonstrating that endocrine disrupting chemicals (EDCs) have the potential to alter sexual development at the organizational and functional level in many species, including humans, indicating that this class of chemicals may play a role in the etiology of transsexualism. Although transsexualism has historically been attributed to social or psychological causes, little data exists to support these claims, thus requiring a closer examination of the evidence regarding changes in sexual development due to EDCs. Toward that end, this thesis considers data from studies examining hormonal signaling mechanisms and changes in sexual development observed in wildlife, laboratory animals, and humans exposed to EDCs, all providing a consistent picture that sex hormones and their receptors are highly conserved evolutionarily, finding similar effects of disruption in many species.

Transsexualism: An Unacknowledged Endpoint of
Developmental Endocrine Disruption? by Christine Johnson, A Thesis: Essay of Distinction Submitted in partial fulfillment of the requirements for the degree, Master of Environmental Studies, The Evergreen State College, antijen.org, June 22 2004.

Image credit Penn State.

In order to place the data in context, a number of historical threads are examined, including: the use of chemicals in agriculture, the use of the pesticide DDT and the pharmaceutical drug diethylstilbestrol (DES), the intertwined relationship between chemical manufacturers and the military, and the history of transsexualism since 1950. The operation and function of the endocrine system is reviewed in order to provide the background to properly interpret findings from endocrine disruptor studies, focusing particularly on the hypothalamic-pituitary-gonadal (HPG) axis. Recent physiological data regarding the vomeronasal organ (VNO) is reviewed, demonstrating that the VNO is the organ responsible for detecting pheromones, or sexually-relevant chemically-based cues, and that exposure of the VNO to extremely low levels of putative sex hormones causes numerous autonomic system responses, including alterations in endocrine function in males. It is therefore suggested that the VNO plays a central role in the circuitry involving sexual development, and a hypothetical framework for testing this concept is provided.

Using this framework, a mechanism for the development of gender identity is proposed, suggesting that gender identity is determined via pheromones by comparing the self with others at an unconscious level. One consequence of this mechanism is that messages conveyed by pheromones can be regarded as signals that can be in contradiction from messages from society, leading to a paradoxical double bind, or a logical contradiction between messages that exist on different logical levels. Another consequence is that there may exist a class of chemicals, pheromone disruptors, that could interfere with pheromones in a manner analogous to endocrine disruptors. Further research must be performed to test this hypothesis since little data exists on pheromones in humans, but early data suggests chemicals may be found that interfere with normal pheromone function.

The prevalence of transsexualism is examined, finding that prevalence differences reported in various countries are not well explained by social factors. Also, it is observed that existing studies have reported the prevalence of transsexuals seeking treatment over a specific time period, but this reporting method is not a measure of the number of transsexuals for each country, which is what the term implies to most people. Several recent epidemiological studies that address sexual changes from endocrine disruption are critiqued, finding that they are plagued with methodological weaknesses and contain a number of errors in interpretation. It is argued that instead of using epidemiological techniques, a more useful approach would be to perform demographic studies that map the birthplace of transsexuals in space and time to determine any patterns that may be related to environmental conditions. The lack of detailed data on transsexual demographics, especially in the United States where such data are completely lacking, has left a void where a lack of data has been interpreted incorrectly as a lack of effect.

The fundamental assumptions used in risk analysis and toxicology are reviewed in the context of recent findings that the effects of a chemical may be larger at low doses than at high doses and that thresholds for the endocrine system must be determined empirically, rather than by assumption of a dose-response curve and extrapolation from an observed toxicological endpoint. The use of invalid techniques by toxicologists has thus invalidated claims of chemical safety, and indicates that public policy based on these techniques are insufficiently protective of public health. Because few things are more important to the continuity of cultures than sexuality and social relations, a number of areas requiring further research are identified, and the need for education of the public is emphasized. I conclude that the existing evidence points towards chemical causes of transsexuality rather than social or psychological causes, requiring a shift in research priorities away from psychosocial studies towards physiological studies of transsexuals.

Hormones, Sexual Development, and Transsexualism

… “this observation raises questions about the validity of existing methods of assessment for studying questions of gender identity development in general. This problem is particularly relevant for offspring of mothers prescribed DES during their pregnancy, since no studies have been performed that specifically asked about changes in gender identity due to these known prenatal exposures to an estrogenic substance.”…

… “The first study was a cohort study of men and women exposed in utero to DES; the study collected demographic data including: age, education, and ethnicity, and psychosexual characteristics including: handedness, sex partner choice, marital status, age at first intercourse, and number of partners.

Interestingly, one finding that reached statistical significance was that DES sons had a higher frequency of left-handedness, which the authors associated with complications during pregnancy; other authors have found that transsexuals also have a higher frequency of left-handedness, suggesting that questions explicitly asking about gender identity status would be appropriate to add to all future studies examining these relations.

However, there are several problems with the study. The format of the study was a survey questionnaire mailed to exposed and unexposed groups, but ultimately, 49% of men and 50% of women from the cohort could not be located, were dead, or chose not to participate in the survey. Consequently, sampling may be biased to an unknown degree because there is no method of determining if those responding are representative of the whole group. Other problems are that all children exposed to DES in utero are assumed to be similarly affected, but because the endocrine disruption thesis suggests that dose and timing is important with regard to outcomes, it is necessary to distinguish when and in what amounts the DES was present in the fetus during critical stages of sexual development. Because the study lacks empirical data regarding prenatal DES exposure, this dramatically weakens the ability of the study to detect differences. Because sexual development proceeds in a number of stages, the timing of the dose is critically important to detecting differences statistically. By considering all those exposed to DES as a homogenous group, effects deriving from exposures during critical periods are obscured, because those exposed outside of these critical windows do not show effects, and therefore they dilute the statistical power of the study. This could be repaired by stratifying the groups by ‘period of exposure’.

Another serious problem with the study is that there is no person in the United States that can be considered a control. As mentioned in the history section, DES was widely used for cattle, thus to a greater or lesser degree, everyone in the U.S. was exposed. Additionally, many other endocrine disrupting chemicals exist, limiting the utility of using a single marker of exposure as an independent variable for changes in sexuality. When these factors are taken into account: high non-response rate, treating all DES exposed persons as a group, and the lack of a proper control, the lack of significance should not be taken as evidence of the lack of an effect.

In a recent teleconference addressing issues of concern to DES sons, Dr. Titus Ernstoff was asked if there were any plans to study gender identity outcomes associated with DES exposure; she replied saying that their study did not have sufficient statistical power to study “rare” outcomes such as transsexuality. However, the DES Sons’ International Network, an internet based research, education, and advocacy group, has found that transsexualism is a common outcome of fetal exposure to DES among sons, indicating that studies on DES exposed persons should be examining endpoints related to altered sexual development. Of their total membership of 600 genetic males, among those who could verify their DES exposure, 52 (8.7%) consider themselves to be transsexual, 26 (4.3%) are transgendered, 9 (1.5%) are gender dysphoric, and 3 (0.5%) are intersex. When all these conditions are considered together, the total rate is 15%, indicating that for DES sons, the frequency of gender identity issues cannot be considered rare. When those who strongly suspect, but who are unable to confirm DES exposure are included, the total number of people who self-identify using one the above categories is 153, or 25% of the network membership.

If the rate of transsexuality in the U.S. is assumed to be 1 in 100,000, and if the number of DES exposed mothers ranges from 3-5 million, the number of transsexuals expected in the entire DES sons population would be 15-25, assuming that DES did not increase the probability of developing transsexualism compared to the general public. Since the DES Sons’ International Network already has double that number of transsexuals alone, this is evidence that among DES sons, the condition is not as rare as Titus-Ernstoff claims, and therefore failure to study the problem may have reasons other than a lack of statistical power – i.e. the decision not to examine the issue may be politically motivated.

Even if a much higher rate of transsexualism in the U.S. is assumed, the numbers do not change very much. For example, if the prevalence of transsexualism in the U.S. is assumed to be the same as in the Netherlands, there should be between 126 and 210 transsexuals in the U.S. due to DES exposure. Because the DES Sons International Network already has 52 transsexuals in their network, this would mean that they have found between 25 and 41% of all transsexuals whose transsexuality can be attributed to DES. Given the membership totals only 600, this seems extremely unlikely, and instead suggests that DES is capable of causing transsexualism, thus explaining the dramatic increase in the frequency of transsexualism in the DES sons group compared to the general public.”

More DES DiEthylStilbestrol Resources

A psycho-endocrinological overview of transsexualism

Is prenatal exposure to DES associated with transsexualism in males?

2001 Study Abstracts

The technical possibility of surgical sex change has opened up a debate concerning the legitimacy and utility of carrying out such an intervention at the request of the transsexual. Diagnostic, psychological, medical and ethical arguments have been brought forth, both for and against.

A psycho-endocrinological overview of transsexualism, European Journal of Endocrinology, US National Library of Medicine National Institutes of Health, NCBI PubMed PMID: 11580991, 2001 Oct.

Image credit goosmurf.

Nonetheless, anatomical transformation by surgical means has currently become a practice as the frequency of serious gender identity disorders is constantly progressing.

After a brief introduction, the present paper will consider typological, aetiological and epidemiological aspects of transsexualism. Treatment of the sex change applicant is then defined and discussed in terms of psychological, psychiatric, endocrinological and surgical aspects. Finally, the question of post-operation follow-up will be examined.

…”Gender identity disorders may be the consequence of an atypical hormonal environment such as congenital adrenal hyperplasia, resistance to androgens or even exogenous hormonal impregnation (the absorption of diethylstilboestrol treatment during pregnancy). In the majority of cases, these subjects do not develop towards transsexualism. Some researchers have documented changes in behaviour (e.g. behaving as a tomboy) and sexual orientation in these subjects, although others have not done so.” …

More DES DiEthylStilbestrol Resources

Sexual differentiation of the human brain

Relevance for gender identity, transsexualism and sexual orientation

2004 Study Abstracts

Male sexual differentiation of the brain and behavior are thought, on the basis of experiments in rodents, to be caused by androgens, following conversion to estrogens.

Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, US National Library of Medicine National Institutes of Health, NCBI PubMed PMID: 15724806, 2004 Dec.

Image credit arselectronica.

However, observations in human subjects with genetic and other disorders show that direct effects of testosterone on the developing fetal brain are of major importance for the development of male gender identity and male heterosexual orientation.

Solid evidence for the importance of postnatal social factors is lacking. In the human brain, structural diferences have been described that seem to be related to gender identity and sexual orientation.

… The importance of the fetal male testosterone surge for sexual differentiation of the brain following aromatization to estrogens agrees with the observations that girls whose mothers were exposed to diethylstilbestrol (DES) during pregnancy run a higher risk of developing bi- or homosexuality. …

… Sex hormones during development also have an influence on sexual orientation, as appears from the increased proportion of bi- and homosexual girls with congenital adrenal hyperplasia. Then there is DES, a compound related to estrogens that increases the occurrence of bi- or homosexuality in girls whose mothers received DES during pregnancy to prevent miscarriage (quod non). DES was given between 1939 and the 1960s to millions of pregnant women. However, these authors could not confirm an increase in the likelihood of homosexual behavior in DES-exposed girls or boys in adulthood. The ratio of the second to fourth finger digits, a measure ascribed to the organizational actions of prenatal androgens, was significantly lower in the homosexual males and females as compared with heterosexuals. This observation suggests that homosexual males and females have been exposed to elevated levels of androgens in utero. …

More DES DiEthylStilbestrol Resources

Prenatal Exposure to Female Hormones

Effect on Psychosexual Development in Boys

1973 Study Abstract

Two groups of boys exposed prenatally to exogenously administered estrogen and progesterone were studied on several parameters of psychosexual development. Subjects were twenty 6-year-olds and twenty 16-year-olds whose diabetic mothers received these hormones to prevent pregnancy complication. Hormone-exposed boys were compared with same-aged boys whose mothers had not received exogenous hormones and matched for age and socioeconomic class.

Prenatal Exposure to Female Hormones : Effect on Psychosexual Development in Boys, JAMA Psychiatry, Obstetrical & Gynecological Survey, doi:10.1001/archpsyc.1973.01750340080013, Volume 28 – Issue 11, November 1973.

Sixteen-year-olds exposed to estrogen and progesterone were rated lower on several variables related to general “masculinity,” assertiveness and athletic ability. Six-year-olds exposed to estrogen and progesterone were rated lower on aggressivity and athletic ability. There were two cases of hypospadias among experimental subjects. While it was not possible to rule out influences other than hormonal which may have influenced results, data suggest that prenatal sex hormone levels may influence some aspects of postnatal psychosexual development in boys.

More DES DiEthylStilbestrol Resources

Time to pregnancy and secondary sex ratio in men exposed prenatally to diethylstilbestrol

Secondary sex ratio in DES Sons

2007 Study Abstract

Little is known about the influence of prenatal diethylstilbestrol (DES) exposure on time to pregnancy or secondary sex ratio in men.

The authors evaluated these associations among men participating in the DES Combined Cohort Follow-up Study for whom exposure status was confirmed by medical record. In 2001, men provided data on their reproductive histories.

Time to pregnancy and secondary sex ratio in men exposed prenatally to diethylstilbestrol, American journal of epidemiology, NCBI PubMed PMID: 17596265, 2007 Oct.

Demographic, behavioral, and medical data were collected in 1994, 1997, and 2001. Cox’s proportional hazards models with frailty were used to estimate fecundability ratios for time to pregnancy in relation to DES.

Generalized estimating equations were used to estimate odds ratios for fathering a male birth in relation to DES. Models included potential confounders and accounted for multiple pregnancies contributed by each man.

Overall, DES was not associated with a delay in time to pregnancy (fecundability ratio = 0.95, 95% confidence interval: 0.86, 1.06). The odds ratio for fathering a male birth was 0.92 (95% confidence interval: 0.80, 1.04) comparing the exposed with the unexposed.

In conclusion, prenatal DES exposure was not associated with a significant decrease in either fecundability or secondary sex ratio.

More DES DiEthylStilbestrol Resources

Secondary sex ratio among women exposed to diethylstilbestrol in utero

Proportion of male births linked to exposure time and dose

2007 Study Abstract

BACKGROUND:
Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio.

Secondary sex ratio among women exposed to diethylstilbestrol in utero, Environnement Health Perspectives, NCBI PubMed PMID: 17805421, 2007 Sep.

Image credit John Flannery.

METHODS:
Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child’s birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies.

RESULTS:
The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at > or = 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at > or = 13 weeks to > or = 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to > or = 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history.

CONCLUSIONS:
Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.

More DES DiEthylStilbestrol Resources

Maternal exposure to DES and sexual dimorphic nucleus volume

Prenatally administered DES impairs testicular endocrine function continuously

2005 Study Abstract

Diethylstilbestrol (DES) was administered subcutaneously at 0.5, 1.5 or 4.5 microg/kg/day (DES 0.5, 1.5 and 4.5 groups, respectively) to pregnant SD rats daily on days 7-21 of gestation, to investigate its effects on the development and functions of the reproductive system in their male offspring.

Effects of maternal exposure to a low dose of diethylstilbestrol on sexual dimorphic nucleus volume and male reproductive system in rat offspring, US National Library of Medicine National Institutes of Health, The Journal of toxicological sciences, NCBI PubMed PMID: 15800398, 2005 Feb.

Image credit photographymontreal.

Of the 10 pregnant rats in the DES 4.5 group, only 1 delivered, and this rat could not suckle the pups. Rat pups in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth.

The testosterone concentrations in the DES 1.5 and 0.5 groups at 6 weeks were significantly decreased and the plasma LH concentrations were not altered. In the DES 1.5 group, DES treatment did not change the volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) in the male offspring, although this dose of DES increased the volume of SDN-POA in female offspring.

The DES treatment altered frequencies in the cycles of the seminiferous tubules, and suppressed histological maturation in the epididymis and the prostate weight.

These observations indicate that prenatally administered DES impairs testicular endocrine function continuously as well as pituitary function, but the induced low level of testosterone disrupts spermatogenesis and permanently inhibits the morphological development of epididymis and prostate.

More DES DiEthylStilbestrol Resources

The Presence of Gender Dysphoria, Transsexualism, and Disorders of Sex Differentiation in Males Prenatally Exposed to Diethylstilbestrol

Initial Evidence from a 5-Year Study

by Scott P. Kerlin, Ph.D., DES Sons International Network,
Presented at 6th Annual E-Hormone Conference, New Orleans, October 27-30, 2004

Introduction and Background

During the 1970s and 1980s an increasing amount of public and scientific attention was paid to the health and medical problems of women and men whose mothers and grandmothers took diethylstilbestrol (DES) for prevention of miscarriage. A potent estrogenic chemical, DES was first developed in 1938 and initially became available in the U.S. for treating a range of gynecologic conditions in 1941 (Apfel and Fisher, 1984). A few years later its approval by the FDA was broadened to include treatment of pregnant women for the purpose of preventing miscarriages (spontaneous abortions). Though its efficacy had long been doubted by some in the medical community (Bambigboye and Morris, 2003; Dieckmann, 1953; Edelman, 1986), DES remained popular until publication of research in the early 1970s identifying an apparent association between prenatal exposure to DES and a rare form of vaginal cancer in females (commonly called “DES daughters”) whose mothers used DES (Giusti, Iwamato, and Hatch, 1995; Heinonen, 1973; Herbst and Bern, 1981).

It is estimated that as many as five to ten million Americans received DES during pregnancy or were exposed to the drug in utero between the late 1940s and early 1970s (Giusti, Iwamoto, and Hatch, 1995). The numbers of male offspring exposed in utero to DES (“DES sons”) have been estimated at between one and three million in the U.S. (Laitman, Jonler, and Messing, 1997) and similar estimates exist for the numbers of American females exposed in utero (Edelman, 1986). Hundreds of thousands of DES sons and daughters were also born in Canada, Europe and Australia during a similar period.

Compared with the history of research on the range of health effects of DES daughters, there are relatively few published medical research studies conducted with DES sons. And yet, the finding that prenatal DES exposure also led to detrimental effects for a number of exposed males has existed since the 1970s (Andonian and Kessler, 1979; Bibbo et al., 1977; Gill et al., 1979; Gill, et al., 1988; Laitman et al., 1997). These effects include a variety of structural abnormalities of the reproductive system such as epididymal (benign) cysts, hypoplastic testes or undescended testes (chryptorchidism), microphallus or underdeveloped penis which may be associated with an intersex condition, and hypospadias (opening of the penis is on the underside rather than at the end). Although DES exposure has been suspected as a possible source of male infertility and testicular cancer (Giusti, Iwamato, and Hatch, 1995, it is still uncertain whether prenatal DES exposure has led to increased risk of infertility (Wilcox et al., 1995) or increased rates of testicular cancer as well as other types of cancer in males (Strohsnitter, et al. 2001).

While published primary studies of other health issues among males with prenatal exposure to DES are not numerous, there is some available research investigating possible links between DES exposure and increased potential for major depressive disorders and other psychiatric effects (Katz, et al., 1987; Meyer-Bahlburg and Ehrhardt, 1986; 1987; Pillard et al., 1993; Vessey et al., 1983). More recent discussion of possible psychiatric effects of prenatal DES exposure, including gender-related effects, has been forwarded by Verdoux (2000; 2002) and Boog (2004). Research investigating possible psychosexual impact of DES exposure in human males (feminization and demasculinization) has been published since the 1970s (Dorner, 1985; Green, 1978; Kester, Green, Finch, and Williams, 1980; Reinisch and Sanders, 1984; Reinisch, Ziemba-Davis, and Sanders, 1991; Yalom, Green, and Fisk, 1973), while research on endocrine disruptors which includes discussion of DES as a possible link in a variety of sexual differentiation disorders in humans has been produced more recently (Boisen, et al., 2001; Gupta, 2000; McLachlan, 2001; McLachlan et al., 2001; Sharpe, 2001; 2004; Skakkebk, Meyts, and Main, 2001; Sultan et al, 2001; Swaab et al., 2002; Toppari and Skakkebk, 1998).

Methodology

This study was initially conceptualized as a one-year (1999-2000) virtual (online) focus group of DES sons from around the world, with the basic purpose being discussion and documentation of the range and history of reported adverse health effects among DES sons. Virtual focus groups are online discussion communities or support groups which, when effectively designed and moderated, enable investigation of a particular issue (for example, adverse health effects) from the perspective of the individuals who are most directly affected (Murray, 1997). The tools and features of online forums like the DES Sons International Network enable a collective engagement of issues raised by participants and fresh insights for participants and researchers.

The DES Sons International Network was developed with a number of primary goals in mind: to bring together an expanding range of individuals born as males who were exposed prenatally to DES, to expand awareness of the range of existing research about DES and male health, and to explore other issues affecting the physical, mental, and reproductive health of DES sons. Most important, it was meant to further investigate still unresolved questions regarding DES sons, consistent with recommendations issued by the National Cancer Institute and National Institutes of Health (National Cancer Institute, 1999).

Upon creation of the DES Sons Online Network (now the DES Sons International Network) in 1999, announcements about the online network were made on a variety of online DES and reproductive health information networks. Subscription requests were carefully screened for

  1. evidence or confirmation of the likelihood of prenatal DES exposure;
  2. confirmation of birth between the late-1940s and early 1970s which was the critical “window” during which DES was administered as an anti-miscarriage drug;
  3. confirmation that the subscriber was born as a male and thus qualified to be considered a “DES Son”.

Although a few other individuals whose exposure status was unknown were permitted to join the Network they are not included in the statistical analysis that is covered in this report.

Data-gathering within this study has used the principles of grounded theory in qualitative analysis which involves a process of continuous expansion and refinement of issues in online discussions, combined with ethical principles of precaution around network members’ identities and privacy. As individuals joined the DES Sons International Network, they provided (privately to the researcher and on occasion in the support group discussions) an overview of health and medical histories as well as other questions or issues surrounding their DES exposure. Primary research on DES sons’ health issues included open-ended questions, occasional surveys or polls of members, periodic online chats (conducted in “real time”) to answer questions on particular health questions such as DES exposure and infertility, and the sharing and posting of relevant published DES research studies in order to generate discussion and further awareness. Summary results from most of the available text-based data are being analyzed using sophisticated qualitative data analysis software.

Within the first year of Network discussions, some members began to raise issues with regard to sexuality, sexual orientation, and gender identity. Over subsequent months, these issues became more substantial in list discussions, at times becoming the dominant themes raised by members. The Network continued to attract interest and new members after the first year and it was decided to continue the Network indefinitely. By the summer of 2004, the DES Sons International Network had more than 200 active subscribers.

As a result of significant attention to gender and sexual diversity issues among some network members, a support group (DES Trans) for these members was formed in January 2002. As of July 2004, more than 130 individuals had joined DES Trans. This underscores the significance of gender identity and intersex conditions as major concerns among a significant portion of persons who have been exposed to DES.

Findings

This section presents an introduction to some of the key findings from research conducted with the members of the DES Sons International Network between July 1999 and July 2004. A more comprehensive summary of the full scope of findings will be completed in 2005.

APPENDIX A

Gender Identity, Sexual Orientation, and Sexual Diversity of DES Sons provides an overview of a January 2002 poll of members of the DES Sons International Network when its total membership was just over 100. Members were asked to indicate the one term pertaining to their gender or sexual identity or sexual orientation that they felt most described how they self-defined among their closest friends. What is significant among the findings of this poll is that among the 63 network members who answered the question (approximately 70% of active network members), the largest number (23, or 36.5% of respondents) identified as “transsexual” (pre- or post-op), while another 15% identified as transgendered, and 13% identified as “intersex” or “androgynous.” “Straight males” represented 17.5% of respondents (the second highest response group), while 13% identified as bisexual or gay males.

APPENDIX B – DES Sons International Network 5-Year Summary Statistics: First Findings

presents an overview of the range of issues raised by the approximately 500 members of the DES Sons International Network during its first five years. (Note re sample size: as of spring 2004, the number of individuals with known or likely DES exposure who have joined the Network since 1999 reached 500 (base sample size = 500). Issues raised by Network members include:

  • Principal Reported Health Concerns of DES Sons
    Based on results from a variety of assessments of individual DES sons in the Network, the three health areas of greatest concern among Network members are (a) hormonal/endocrine health issues; (b) gender identity and sexual health issues; and (c) psychological/mental health issues including anxiety and depression.
  • Additional Reported Adverse Health Effects
    Members identified a range of adverse health effects including autoimmune disorders, infertility, reproductive tract abnormalities, ambiguous or underdeveloped genitalia, epididymal cysts, testicular cancer, and erectile dysfunction.
  • Significant Gender Dysphoria Prevalence
    Somewhere between one-quarter and one-third of members of the DES Sons’ network since 1999 have indicated that gender dysphoria, transsexual outcomes, and/or sexual health issues were among their top concerns.
  • Relatively High Prevalence of Transsexual, Transgender, and Intersex
    More than 150 network members with “confirmed” or “strongly suspected” prenatal DES exposure status indicated they are either transsexual (pre- or post-operative, 90 members), transgender (48 members), “gender dysphoric” (17 members), or intersex (3 members).
  • Low Cancer Prevalence
    Only a small number of DES sons contacting the network have reported experiencing any type of cancer-related health problems (primarily testicular cancer during younger years).

Discussion and Implications

During the first five years of research within the DES Sons International Network some important accomplishments and discoveries have occurred. These will be more thoroughly detailed when a subsequent edition of this paper is completed in 2005. Accomplishments and a brief examination of the implications include the following: through the first five years of this study a base sample of 500 individuals with confirmed or “suspected” DES exposure from a wide range of locations around the world has been obtained.

Historically, research with DES sons has often entailed relatively low numbers of individuals, making it difficult to extrapolate from one study to broader populations of DES sons. The research in the DES Sons International Network, while involving relatively low levels of researcher control over issues of geographic location or dosage/timing of exposure, has enabled deeper exploration of issues of common life experience and human development among DES sons. Grounded Theory (Glaser and Strauss, 1967), as a rigorous method of qualitative inquiry in which theory is developed inductively from a corpus of data, was used in this study to enable issues to emerge that otherwise might be overlooked in study designs involving greater levels of control.

Endocrine system disorders such as hypogonadotropic hypogonadism in DES sons have been among the most common reported adverse health effects in this research study.

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

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

Our findings support the efforts, most recently by Verdoux (2000, 2002), to obtain better understanding about the risks and causes (if any exist) of psychiatric disturbances among DES-exposed individuals. It is hopeful that future research on human health effects of exposure to endocrine disrupting chemicals (i.e. assessing neurotoxicity) will include psychiatric disturbances such as major depression, anxiety disorders, eating disorders, and psychoses as potential endpoints for analysis. 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.

Relative infrequency of reported cancer among the DES sons in this research is consistent with most existing long-term studies demonstrating there is limited cancer risk in males directly due to prenatal DES exposure.

While the rate of total cancer occurrence in the DES Sons International Network could not be rigorously measured, numerous efforts have been made to generate discussion about cancer risks and in particular, to encourage dialogue regarding testicular cancer experiences. Approximately five 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. in 2001.

One of the most significant findings from this study is the high prevalence of individuals with confirmed or strongly suspected prenatal DES exposure who self-identify as transsexual, transgender, intersex, or who have identified serious difficulties with gender dysphoria.

Throughout this study, the issue of gender dysphoria (Colucciello, 1996) and the prevalence of a significant number of self-identified male-to-female transsexuals (Cohen-Kettenis and Gooren, 1999) and transgendered individuals (Conway, 2004) as well as some individuals who identify as intersex, androgynous, gay and bisexual has raised fresh awareness of historic theories of a possible biological/endocrine foundation to variations in psychosexual development in humans (including sexual orientation, core gender identity, and sexual identity). Some of these theories were first forwarded in the 1960s by experts in sexual medicine (Benjamin, 1966,

1973; Diamond, 1965, 1996) and have been further refined relative to the role of hormones in shaping gender-based behavior and sexual orientation (Dorner, 2001; Friedman and Downey, 2002; Wilson, 1999; Michel, Mormont and Legros 2001; Rudacille, 2005). The discoveries in this study suggest that gender dysphoria and transsexual changes may be a plausible toxic endpoint for future exploration of the human health effects of exposure to endocrine disruptors. Further, they call into question the accuracy and adequacy of previous research and conclusions by Titus-Ernstoff et al. (2003) in which they conclude that there is little support for a hypothesis that prenatal DES exposure influences psychosexual development in males and females (Udry, 2003).

The findings in this study relative to developmental abnormalities of the male reproductive tract substantiate previous research on prenatal DES exposure and various structural deformities in some DES sons and lend new support for the hypothesis that endocrine disruptors may have substantial negative effects in human males.

In underscoring the human health effects of prenatal exposure to DES in males, the findings in this study are consistent with McLachlan’s (2001) proposition that DES be considered as a model for developmental estrogenization.

This paper has provided a brief encapsulation of the leading trends and outcomes from a preliminary review of results from a five-year study of DES sons. Many of the issues and questions deriving from this study will be further examined and refined during 2005. Interested researchers are invited to join the DES Research online group located here.

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Prevalence of Transsexualism, Transgenderism, Gender Dysphoria, or Intersex among DES-Exposed

DES Sons International Network Statistics of Individuals with Gender-related Issues or Outcomes Among Network Members

Scott Kerlin, 5-Year Research Summary Update, October 2004

Among the population of DES sons in our network who have raised gender-related questions and experiences, I have received personal stories and/or introductions from more than 150 individuals with either confirmed or “strongly suspected” DES exposure. Among 158 “likely DES-exposed” persons (confirmed or suspected), their summary descriptions of identity and/or experiences reflected the following.

There have been at least 93 individuals with confirmed prenatal DES exposure who indicated they are either transsexual, transgendered, gender dysphoric, or intersex. (These terms come from individuals’ self-description of their identities or primary health concerns.) Here is the distribution of those 93 individuals:

  • Confirmed DES-Exposed and Gender-Related Issues (N=93)

    1. Confirmed Exposed and Transsexual:                     54 individuals
    2. Confirmed Exposed and Transgender:                   26 individuals
    3. Confirmed Exposed and Gender Dysphoric:        10 individuals
    4. Confirmed Exposed and Intersex:                                3 individuals

There have been at least 65 individuals with “strongly suspected but not yet confirmed” exposure who indicated they are either transsexual, transgendered, gender dysphoric, or intersex. Here is the distribution of those figures:

  • Strongly suspected, not confirmed DES Exposed and Gender-Related Issues (N=65)

    1. Suspected Exposure and Transsexual:                    36 individuals
    2. Suspected Exposure and Transgender:                   22 individuals
    3. Suspected Exposure and Gender Dysphoric:          7 individuals
    4. Suspected Exposure and Intersex                            none reported

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DES Sons and the Significance of Gender Identity

DES Sons International Network Statistics of Individuals with Gender-related Issues or Outcomes Among Network Members

Scott Kerlin, 5-Year Research Summary Update, October 2004

  1. Within a few months of the formation of the Network in 1999, several members raised issues regarding gender dysphoria as among their (apparent) side effects. Over time this issue became more common in private disclosures to me by members, as well as online group discussions. Over time, gender identity issues and transsexualism emerged in discussions among regular DES Sons International Network members. Ultimately because of the sensitivity of many gender-related discussions, some members wished to have a more private discussion environment separate from the main DES Sons International Network. In January 2002 I formed the DES-Trans Gender Support Group (DES-Trans) for more extensive discussions of these issues.
  2. Somewhere between one-quarter and one-third of members of the DES Sons International Network since 1999 have indicated (through my private surveys and/or interviews of members, membership poll responses, or through personal introductions and subsequent discussion postings to the Network) that gender identity and/or sexuality issues were among the most significant issues they needed to understand or seek further support.
  3. The majority of individuals who joined the Network (i.e. somewhere between 2/3 and 3/4 of the total, or about 350 persons) did not mention gender issues or concerns during their personal introductions, health histories, or subsequent Network discussions. I have no way of knowing how many of these individuals may also have gender-related issues, unless at a subsequent time they have chosen to raise them (as some have in private correspondence with me). I suspect there are others for whom it is an underlying concern but not an easy for them to articulate without fear of ridicule or dismissal from others.
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