Tag Archives: off label

Would You Do Anything (Dangerous) To Make Sure Your Baby Wasn’t Intersex?

Debbie says:

I never blogged Alice Dreger‘s fascinating TED talk, “Is Anatomy Destiny?” on biology, bioethics and gender when I watched it last year, but her name stuck in my memory. The talk is available at the link, and I recommend it highly.

Now she and two co-authors have published a truly horrific situation in the Journal of Bioethical Inquiry. Apparently, dexamethasone is being given “off-label” (that’s pharmaceutical-speak for “a way that it has never been tested or approved”) to pregnant women whose children may be “at risk” for intersexuality issues!

The pregnant women targeted are at risk for having a child born with the condition congenital adrenal hyperplasia (CAH), an endocrinological condition that can result in female fetuses being born with intersex or more male-typical genitals and brains. Women genetically identified as being at risk are given dexamethasone, a synthetic steroid, off-label starting as early as week five of the first trimester to try to “normalize” the development of those fetuses, which are female and CAH-affected. Because the drug must be administered before doctors can know if the fetus is female or CAH-affected, only one in eight of those exposed are the target type of fetus.

The off-label intervention does not prevent CAH; it aims only at sex normalization. Like Diethylstilbestrol (DES) — which is now known to have caused major fertility problems and fatal cancers among those exposed in utero — dexamethasone is a synthetic steroid. Dexamethasone is known — and in this case intended — to cross the placental barrier and change fetal development.

Let’s unwrap this:

Dexamethasone is a very powerful drug, used for a wide variety of different conditions. The only case in which it is used early in pregnancy is this one. It is used late in pregnancy to aid in fetal lung development in cases of expected premature birth. Even there, it is risky and associated with low birth weight, but not premature fetal death (as of a 2001 study).

Use of DES, a compound with a similar chemical signature, caused one of the worst stories of medical interventions in pregnancy. DES was used off-label to prevent miscarriage (which there was no evidence that it did) for more than 20 years and “aggressively marketed and routinely prescribed.” Up to 3 million pregnant American women were given DES. Since that time, having a mother who was given DES has been repeatedly proved to vastly increase the risk of certain cancers and somewhat increase the risk of other cancers, increase the risk of various deformities and also have some sexual/gender effects on the baby. “DES daughters” and “DES sons” are both affected, and the drug also may have increased the frequency of intersexual babies.

CAH, the condition that dexamethasone does not prevent has two major effects. First, it can be very dangerous to newborns because of how they metabolize salt. Dexamethasone won’t solve this.

Second, it can cause intersexual traits and increase of testosterone in babies who are genotypically female (and have full female reproductive systems). Signs of this include an enlarged clitoris and a shallow vagina. Dexamethasone may affect this.

So, here’s the bottom line:

1) Dexamethasone is being given to women before there is any evidence that their babies are female, let alone have CAH, so it is only “effective” for one in 8 babies.
2) Dexamethasone does nothing for the actively dangerous aspect of the condition it is supposedly treating.
3) We know little or nothing about the effects of dexamethasone in terms of causing either cancer or birth defects. However, the chemical similarities between DES and dexamethaosone raise the specter of long-term horrible effects on babies whose mothers take dexamethasone during pregnancy.
4) The concern that a girl baby might be “virilized,” i.e., have a big clitoris, increased testosterone, and possibly male secondary sex characteristics like facial hair somehow balances the first three points.

I really wonder how many women would say, “Yes, give me the drug” if a doctor looked them in the eye and said, “This drug might give your baby a more conventionally shaped clitoris and vagina, but it won’t help her in any other way. It won’t do anything positive for your baby if he’s a boy. And it might cause anything from deformity to early death from cancer.” But, of course, that’s not how doctors who think the drug is a good idea will frame the choice. And very few doctors are going to say, “If your otherwise girl baby has a big clitoris, a shallow vagina, and high levels of testosterone, she can have a great life!”

So thanks to Alice Dreger and her co-authors, Ellen Feder and Anne Tamar-Mattis, for pushing back against the ridiculous levels of social terror when faced with variety in genitals and hormone levels. I only wish they had as much power as the pharmaceutical companies and medical establishments they are opposing.