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DES Action PublicationsFocus on Stilboestrol Newsletter Autumn 2010 Unlocking the Mysteries of How DES Causes Harm (reproduced by permission of the VOICE, DES Action USA Spring 2009 #120)) “Hypermethylation of HOXA 10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming,” Hugh S. Taylor, et al, Endocrinology, March 19, 2009 as doi:10.1210/en.2009-0071 Reviewed by Fran Howell We know of the havoc caused by DES when introduced to a developing fetus: abnormalities of the female and male reproductive tracts, infertility problems, and cancers of the vagina, cervix and breast, among other health issues. Now researchers at the Yale School of Medicine are zeroing in on why DES acts the way it does. The team, led by Hugh S. Taylor, M.D., professor in the Department of Obstetrics, Gynecology and Reproductive Science, exposed pregnant mice to DES and studied their female offspring. He was particularly interested in the HOX gene family, which regulates development. One in particular, The HOXA10 gene directs embryonic uterine development. Earlier studies by Taylor and others have shown that prenatal DES exposure alters the process called methylation. That is how genes are switched on and off at certain times to do what they are programmed to do. The genes themselves are not changed or mutated, but rather, the way they function or express themselves is altered. DES was known to disrupt the process, but it wasn’t understood exactly how. Taylor focused on the HOXA10 genes from DES Daughter mice because they act as important regulators of tissue identity. Alterations in HOX gene expression cause abnormalities in tissues that depend on those genes for proper development. According to Taylor, altered gene expression, or methylation, has been associated with reproductive tract abnormalities, such as those seen in DES Daughters and Sons, along with human cancers in adulthood. This research examined how HOXA10 gene expression is altered by in utero DES exposure. What he learned is that in utero exposure to DES results in methylation of the HOXA 10 gene, causing it to be lower in areas where it is normally required for uterine development and higher in areas where it should not be expressed. One of these areas is the vagina. This finding perhaps explains the vaginal adenosis common in DES Daughters; The HOXA 10 gene is more active than it should be during development of the fetus. Reproductive tract abnormalities experienced by many DES Daughters are now suspected to be the result of lower or higher functioning of this gene. Also noted is that the DES-caused hypermethylation of the HOXA10 gene in utero does not cease after birth. Taylor found that prenatal DES exposure “results in lasting changes in gene expression, persisting well after exposure, into adulthood.” This helps explain why developing fetus exposed to DES might develop cancers and other health issues many years after exposure. By zeroing in on how prenatal exposure to DES causes the hypermethylation of certain genes, scientists are moving forward with a better understanding of why DES causes the problems it does, both at the time of exposure and also decades later. Did You Know ? <> DES Was Never Banned For Human Use Time To Set The Record Straight In 1971, after DES Daughters were diagnosed with a rare cancer, the FDA told doctors to stop prescribing DES to their pregnant patients. But the drug was NOT banned for human use. Some doctors did not get the message, while others chose to ignore it. We are now learning of cases in which DES was prescribed well past 1971 in the USA and also into the 1980s internationally. Of note is that back in 1959, DES was banned from animal feed given to chickens and lambs after high DES levels produced side effects. They included male breast growth in humans who worked with these animals. But DES prescriptions continued being written for women! It wasn’t until September 30, 2000, that the FDA finally withdrew its approval of DES for humans. By then, no doctors were prescribing it anyway. But DES was NEVER BANNED for human use, despite what you may have heard!
Editorial While the above piece referred to the USA, the situation in Ireland was the same, if not worse. Because there were no official warnings issued here by the National Drugs Advisory Board, word of the dangers of DES use in pregnancy took a couple of years to filter through. By the mid 1970s, its use was declining but as in the USA, there were some doctors who thought they knew better than the perceived wisdom! Have the obvious lessons been learned? For some time we had discussed how best to remember our good friend and treasurer, Colette Egan. We decided to present a framed painting to the National Maternity Hospital to be hung in a public area. On January 20th this year, 2010, we presented “the Phlox Garden” by Mildred Anne Butler to the staff who, over the years, have looked after many DES daughters. Colette’s brother Frank came with us and we were entertained to a delicious trolley lunch. The painting is hanging in the gynaecology waiting room, with the inscription “remembering Colette Egan, friend of DES Action and the DES clinic”. Don’t forget to admire it the next time you are in the vicinity. Enclosed you will find notice of our up-coming Annual General Meeting on Tuesday, September 28th 2010. Please come along if you can, we would welcome feed back from our members and suggestions for the future. As the age profile of our DES daughters moves on, we receive fewer calls to our line but we continue to provide the information and advice when it is sought. Much of our budget is spent on keeping our telephone line operational. Thank you for your continuing support. Daphne Passmore, Editor
DES Action Ireland
Daphne Passmore, Editor.
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BooksYou may find the books listed below to be of value. The books can be ordered online from Amazon. If ordered via the links below, a small commission will be paid to DES Action Ireland.
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