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Prenatal treatment for genetic gender disorder questioned

12 July 2010
Appeared in BioNews 566

In August, the Journal of Clinical Endocrinology & Metabolism will publish an article on a consensus reached by the American Academy of Pediatrics, the European Society for Paediatric Endocrinology and many others, regarding the controversial use of dexamethasone (dex), a steroid used to treat a genetic condition called congenital adrenal hyperplasia (CAH), which can affect one in 15,000 babies.

The consensus paper will state that prenatal treatment with dex must only take place in trials that are pre-approved by institutional ethic review boards and that can gather meaningful data.

Fetuses affected by CAH are unable to make an adrenal hormone called 21-hydroxylase, which results in the adrenal glands producing an excess of male hormones. In boys this does not affect the sexual organs, though it can trigger early puberty. One in eight affected girls, however, will develop masculinised genitalia such as an enlarged clitoris or the positioning of the urethra inside the vagina. This can be treated with corrective surgery after birth.

Dr Maria New, a paediatric endocrinologist from the Mount Sinai School of Medicine, New York, has for many years been studying a treatment that prevents the anatomical abnormalities associated with CAH while the fetus is still in the womb, by giving dex from five weeks after conception for women with fetuses at risk of CAH. Dex can reduce male hormone levels, resulting in normal anatomical development, though it does not cure CAH - the affected individuals will still need to take medication for the rest of their lives.

In a related study, Dr New's collaborator, Dr Heino Meyer-Bahlburg of Columbia University, is examining how dex may affect cognitive behaviour in females with CAH, after studies in animal fetuses showed high levels of dex may damage the central nervous system. Earlier this year, Dr New published a paper in the Annals of the New York Academy of Sciences, in which she and colleague Dr Saroj Nimkarn of Weill Cornell Medical College, spoke about the potential effect of dex treatment on the behavioural masculinisation of girls affected by CAH.

The studies have attracted criticism from Professor Alice Dreger of the Northwestern University Feinberg School of Medicine, Chicago, and others at the Bioethics Forum, New York. They are concerned that dex will in the future be used in a misguided attempt to alter the behaviour rather than anatomical defects of children with CAH; girls with CAH are supposedly more likely to be 'tomboyish', homosexual or bisexual. In a paper entitled 'What Causes Low Rates of Child-Bearing in Congenital Adrenal Hyperplasia?' Dr Meyer-Bahlburg wrote that 'CAH women as a group have a lower interest than controls in getting married and performing the traditional child-care/housewife role.'

There are also questions about whether the 600 pregnant women given dex by Dr New's team had properly consented to the full implications of the treatment. So far, only one small study has been done on the potential long term effects of treating fetuses with dex. 'We just don't know what we are doing to these kids,' says Dr Walter Miller, chief of endocrinology at University of California, San Francisco.

Despite the concerns, many of which could be addressed by the recommendations being made in the consensus paper, most researchers agree that using dex to try to correct anatomical defects prenatally is justified and is far preferable to surgery after birth. For example, Professor David Sandberg of the University of Michigan in Ann Arbor says: 'It would be wrong to simply say stop.'

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