The conundrums of ambiguous genitalia begin with nomenclature. Should we call it “ambiguous genitalia” anymore? Experts say no. They recommend “disorders of sex development.” The big advantage of that seems to be that nobody knows what it means so it doesn’t piss anybody off. Yet.

I miss “hermaphroditism.” It has a delightful pre-code feel to it. It suggests something exotic and Greek.

Clitoromegaly? Well, that is by far the most common of the disorders of sex development. It is usually associated with congenital adrenal hyperplasia (CAH), an enzyme defect that causes virilization. In girls, that means clitoral enlargement. In boys, it means enlargement of the penis but shrinkage of the testes (or, as the medical student mnemonic, LMNOP, helps us to remember it, “Lots of meat and no potatoes.”)

CAH is associated with a host of medical problems, some of which are life threatening in the newborn period, so early diagnosis is very important. It can now be diagnosed prenatally. Clitoromegaly is not one of the life-threatening problems but many people find it disturbing, especially in the more extreme cases in which the urethra emerges through the clitoris, the clitoris resembles a penis, and the external genitalia look more male than female.  

Such anatomic variations raise the following ethical question – is the fact that some people are disturbed by such variations a good reason to try to prevent them? That question quickly reduces itself to a second question – are people disturbed because they think it is bad for the baby (or child or adult) to have such anatomy, or are they disturbed because they, themselves, find the anatomic variations troubling?  If the latter, the solution would seem to be psychotherapy for those who are disturbed. If the former, then the solution of giving preventive medicine to the fetus is preferable.

The question, then, of whether it is bad for the baby to have ambiguous genitalia is one that would seem to be a factual question. What bad outcomes are anticipated? How common are they? Does treatment prevent them? And if it does, is the treatment associated with side effects that might outweigh the benefits?

These ethical questions came to the fore recently in a heated debate on the use dexamethasone, a steroid given to pregnant women to prevent the cosmetic manifestations of CAH in their unborn daughters. A recent Bioethics Forum post expressed strong opposition.

Unfortunately, getting the factual answers that might allow a dispassionate resolution of the debate is well-nigh impossible. To see why, one must imagine the study that would give those answers. Ideally, we would have a group fetuses that have either been diagnosed with – or are at risk for -- CAH. We would then randomize them to prenatal steroids (which can prevent the virilization and the resultant anatomic changes) or to placebo.

We would then follow the two groups through childhood and for 25 years (or 50, why not?) and see how they scored in school, what their marital lives were like, and how they did on various measures of emotional and sexual well-being at different points in their lives. Then, we would know, once and for all, whether the benefits of treatment outweighed the harms and the burdens.

The study has three problems. First, nobody would sign up for it, because most people have strong opinions about the desirability or undesirability of treatment. Second, IRBs may not approve it, because the same lack of equipoise that would prevent people from signing up would prevent IRBs from deciding that randomization is appropriate. Third, most people have already made up their minds, based on existing, uncontrolled data, about the risks and benefits of prenatal dexamethasone.

Even if those problems could be overcome and the study carried out, the results would not be available for 25 or 50 years. By then, nobody except medical historians will even remember the clumsy and barbaric things that we once did, since, by then, every zygote will be screened for anomalies and CAH will have gone the way of smallpox.

In the meantime, we live with radical and irreducible epistemic uncertainty. We don’t know – and cannot know – whether some fetuses or babies or all fetuses or babies with the anomalies associated with CAH will be better off treated or untreated. We can take a naturalistic view – if it ain’t broke, don’t fix it – or an interventionist view – if it ain’t perfect, make it better – but either view will be based upon presuppositions that have nothing to do with data.

Ah, you say, but there is data on the harms of prenatal steroid treatment. Not much. The best studies come out of Sweden. They have done long-term follow-up on fetuses that were treated with dexamethasone and compared them to matched controls.

The numbers were small – 30 or so in each group. They found, “There were no statistically significant differences between DEX-exposed children and controls in measures of psychopathology, behavioural problems and adaptive functioning.” They also found no differences in “psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory.”

There were some differences in short-term memory: “Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child's full-scale IQ.”

The differences in short-term memory are concerning but, in a small, non-randomized, trial that compared dozens of different measures, they are hard to interpret. The chance of finding something significant between the two groups was high just because so many things were compared. One also wonders whether they reflect the effects of the treatment or the effects of the disease, since the control group, though age-matched, did not have CAH. It is hard to find an untreated control group, for all the reasons stated above, and it would be impossible to find a randomized control group, since everybody already has strong opinions about what is best and nobody thinks that flipping a coin is the way to decide.

So, what is to be done? This seems to be a conundrum where the best solution is to trust the marketplace of ideas and the marketplace of medical treatment. Insist on informed consent. Put information out there on Web sites. Keep as many lines of communication open as possible. And let parents decide.

Neither prenatal treatment with dexamethasone, nor no treatment, seems so heinous as to be forbidden. For better or worse, we live in a world where alteration of the appearance of one’s child’s genitals in a way that doesn’t interfere with sexual function is a parental prerogative.

John Lantos, M.D., is director of the Children's Mercy Bioethics Center and professor of pediatrics at the University of Missouri at Kansas City.