incomplete expression of testicular feminization syndrome (AIS, CAIS or PAIS) with the defect affecting only sex- specific areas of the hypothalamus…. Recent research indicates that in the genetic male the hypothalamus is masculinized by fetal androgen at a specific period somewhat after the masculinization of the genitourinary tract. The genetic female, with her XX chromosome complement, lacks fetal androgen and therefore develops along typically female patterns. The important principle here is that effective androgen is necessary for masculinization. Without androgen, masculinization will not occur. Thus, the prenatal hormonal environment is critically important for all future development.”
Over the past three years, as I’ve researched this book, I’ve been struck by the fact that most of my sources trace their feelings of gender dysphoria to their earliest childhood. Sometimes their intuition of the disjunction between their bodies and their sense of themselves as boys or girls is their very first memory. They can recount exactly where they were and what they were doing when they first admitted to themselves that they were not the children that others assumed them to be—usually before the age of five. Many transgendered people believe that these feelings (which in the case of transsexuals are so overwhelming that those who experience them eventually seek surgical and hormonal sex reassignment) are the result of “hormone surges” in prenatal life that somehow alter the link between their physical sex and their gender identity. More than one person I interviewed compared transsexuality to a cleft palate—characterizing both as “birth defects” that require surgical intervention. A few mentioned the increased incidence of reproductive deformities and “transsexualism” (feminized males, masculinized females) in wildlife and wondered if there might not be some connection to their own situation. But few are willing to state as bluntly as Christine Johnson that their lives and gender identities may have been turned inside out by an environmental toxin.
In March 2002, I asked the subscribers of the National Trans Advocacy Coalition’s online discussion list what they thought of the environmental endocrine hypothesis as a possible explanation for their gender variance. I received some interesting replies. Rozlyn Manley, a Vietnam veteran who worked as a claims adjuster prior to her transition, posted the following response.My former career was in the insurance industry, where I handled high- exposure claims on behalf of the international insurance market. Among those claims were pollution, environmental, and product liability claims. In addition to managing the defense and negotiation of existing litigation, I was also in constant contact with the Fortune 500 companies regarding potential litigation they were concerned with. This is because they self-insure the first five or ten million of coverage and have a duty to keep the excess insurers fully informed of what was in the pipeline. Before I left, I began hearing from the pharmaceutical and petro-chemical companies about “gender bender” claims. Each have waste by-products that they dispose of in settling ponds, mostly in Puerto Rico, Germany and our Gulf Coast. They were becoming aware of animals displaying homosexual behavior and transsexual changes. For example, female birds in the Gulf Coast were nesting with each other and non-mating with the male birds. Marine and land animals were displaying distinct transsexual changes in their external genitalia and internal organs. We, of course, are all aware that human male sperm count has been rapidly declining during the last few decades. There are claims being filed against these companies, and they are concerned. At least when I left, they had a working hypothesis but no specific proof of what was going on. None of this says that our trans condition is solely the result of someone’s negligence, but it may indicate that something occured that may have trigged our propensity.Another example might be my hometown of Huntingdon Beach, California. When I graduated in 1964, the population was about 10,000 and there were 2,000 students in the high school which served the surrounding counties. I can now identify 18 post-op transsexuals that graduated between 1964 and 1975. Clearly, this rate is far beyond the generally expected incidence of transsexuality. Is this simply an example of the rule of large numbers, or could it be that Huntingdon Beach had its own aquifer, and it is severely polluted from oil drilling and is no longer used for drinking? I won’t begin to state that one led to the other. I simply do not know. I do believe, however, that by sharing these occasional tidbits, some biochemist or geneticist just might have their “idea bell” ring. What follows will be for the next generation to benefit from.
Vanessa Edwards Foster, the chair of the NTAC Board, responded:Wonderful! For years, I lived just
Julie Maverick, the university professor who chairs the National Transgender Advocacy Coalition’s research committee, told me that there are valid scientific hypotheses that link transsexual behavior and physiology in many animals to endocrine-disrupting chemicals and hormones in the environment. “These include fish, frogs, and alligators,” says Maverick. “Endocrine-disrupting chemicals have also been linked to malformation and malfunction of sexual organs in these animals and there is some evidence, though not much and mostly anecdotal, to suggest a higher incidence of transsexualism in humans due to elevated exposure to various organic chemicals, particularly DES.” However, Maverick said that at present it would be rash to assert a causal relationship between these chemicals and transsexuality, cross-dressing, or any other form of anomalous gender identity or expression. “To claim any causal link is decidedly premature. Rather, it [existing data] should foster research in this area.”
The science of endocrine disruption is still in its infancy, so it is not surprising that no one has investigated possible links between human gender variance and exposure to EDCs. In some ways, “the concept is ahead of the science,” says my friend Jim Yager, senior associate dean for academic affairs at the Bloomberg School of Public Health at Johns Hopkins University. Yager, a toxicologist, has been studying the relationship between estrogens and breast cancer for more than two decades, and even in that well-studied endeavor there have been no definitive data establishing causality between exposure to EDCs and rising rates of breast cancer. Yager says that one of the challenges researchers have encountered in EDC research is that “we’re seeing [biological] effects at concentrations that we couldn’t even detect ten years ago.” Much of the laboratory research thus far has been carried out in vitro, and while it is clear that there are measurable biological effects on cells exposed to various EDCs, and on gene expression within those cells, “you can see an effect, but is it a biologically meaningful effect?”
Then, too, “estrogens are considered reversible cellular signals,” as John McLachlan writes in a 2002 review titled “Environmental Signaling and Endocrine Disruption,” meaning that when the estrogen is withdrawn, the effects of the estrogen fade—as any trans person who has gone on and off hormones could testify. “On the other hand, when estrogens are given to newborn mice, at least one gene under estrogen control is expressed persistently, even in the absence of estrogen,” McLachlan notes in the paper. “This leads to the question, how does a reversible signal became irreversible in the absence of a detectable gene mutation?” McLachlan says that “the actual mechanism underlying the molecular feminization of genes by estrogen still has not been elucidated.” Nonetheless, studies have shown that estrogen can “imprint” genes in such a way that “when a gene programmed to respond to estradiol at puberty is misprogrammed or reimprinted by developmental exposure to a hormonally active chemical, it will respond abnormally to the secondary cue, resulting in a functional cellular abnormality.” This process has been elucidated most clearly in chicken and frogs. But it does lead one to wonder what might be the effects on human fetuses whose gene expression may have been chemically altered by exposure to estrogens in the womb and who are then re-exposed again and again to estrogenic chemicals in the environment?
It’s a long way from cells in a dish to a complex human trait such as gender identity, but the path from cell to animal to human in biomed-ical research is a well-traveled one. The neurological basis of psychiatric conditions once considered the result of inadequate parenting (schizophrenia) or insufficient willpower (alcoholism and other addictions) is now recognized, even if the mechanisms that produce the condition remain incompletely understood. McLachlan points to one interesting example of a behavioral disorder gradually revealed to be a signaling problem in “Environmental Signaling and Endocrine Disruption.” The condition, once called “St. Anthony’s fire,” is today called
