The Riddle of Gender - Deborah Rudacille [139]
We agreed to meet in the spring, to discuss these issues in more detail. In the meantime, I learned that colleagues at the Johns Hopkins
Bloomberg School of Public Health were holding a workshop on endocrine disrupters in February 2002. The workshop would bring together scientists from industry, academia, and regulatory agencies from the United States and abroad to discuss progress in identifying and testing hormonally active substances, and ways to implement those goals that would not require a massive animal testing program. I was particularly interested to see that one of the speakers at the meeting was Dr. John McLachlan, the Tulane University researcher considered one of the primary architects of the environmental estrogen hypothesis. McLachlan has been studying the effects of endocrine-disrupting chemicals for over thirty years. I approached him after his presentation at the February 2002 meeting and asked him, with some trepidation, if it was possible for endocrine-disrupting chemicals to affect human gender identity and sexual orientation, and to increase the prevalence of intersex conditions.
“Absolutely,” he replied, pointing out an already documented increase in the incidence of hypospadias (incompletely differentiated penis) in baby boys. Having studied the effects of endocrine-disrupting chemicals on one-celled organisms, fish, reptiles, and mammals for more than two decades, McLachlan said that he can predict with some certainty what effects endocrine-disrupting chemicals will produce when administered in sufficient doses to animals at critical stages in fetal development. But he also said that no one has yet linked these effects, which have been confirmed in laboratory animals and wildlife, to the development of gender identity or sexual orientation in humans. “You should have a look at the DES literature,” he said. Soon after the meeting, I did so. What I discovered astonished me.
DES was first synthesized in 1938, in the laboratory of Sir Charles Dodds, a professor of biochemistry at the Middlesex Hospital Medical School at the University of London. Researchers working independently in England and Germany had succeeded in isolating natural estrogens for the first time in 1929, but natural estrogens were very expensive and difficult to produce. Further, the supply of natural estrogens could not meet the demand; Dodds’s discovery of a synthetic estrogen that could be easily and cheaply produced was hailed as a great boon. Dodds and his colleagues tested the effects of this new synthetic estrogen on female rats that had first undergone ovariectomy (removal of the ovaries). The ovariectomized rats responded to DES as though it were an endogenous estrogen produced by their own bodies—even though DES, manufactured from coal tar products, is not at all chemically similar in structure to natural estrogens. Indeed, DES appeared to be even more potent than natural estrogen, mimicking its biological effects when ingested in much smaller doses.
Within a year, DES was being manufactured and marketed in mass quantities by drug companies in Europe and North America. Never patented, the drug was sold under more than 400 different brand names by 257 pharmaceutical companies in the United States alone. DES was used as “hormone replacement therapy” for women, and was approved by the U.S. Food and Drug Administration for that purpose (among others) in 1941. DES was also initially prescribed to suppress lactation in the growing number of women who did not wish to breast-feed their infants, to treat amenorrhea (failure to menstruate) and vaginitis, and (surreptitiously) to prevent miscarriage, though it was not approved for the last purpose in the United States until 1947.
The use of DES to prevent