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First, the OMGWTFBBQ. Via Pharyngula, the Hastings Center Bioethics Forum, and TIME Magazine: pediatric endocrinologists Maria New and Saroj Nimkarn are advocating prenatal treatment with the glucocorticoid dexamethasone to "reduce behavioral masculinization" of female children.

Yes, you read that right: they want to expose pregnant mothers to one of the most potent, adverse-effect-prone steroids out there in the hopes of molding unborn girls into models of femininity.

I'll give you a few minutes to find where your lower jaw rolled off to and get a glass of water -- throwing up in your mouth a little is bad for your teeth. When you get back, I'll expand a little on the current standards of practice, and then we're going to go over some organic chemistry.

Back now? Great. First, PZ got one important fact wrong: the American Academy of Pediatrics and other noteworthy medical organizations have absolutely not condoned or endorsed this practice. The "consensus" to which PZ refers is an agreement that the study of dexamethasone as a preventative for congenital adrenal hyperplasia due to 21-hydroxylase deficiency should be conducted "via IRB-approved clinical trials through research centers large enough to obtain meaningful data" and with follow-up studies. This is, in my opinion, a reasonable position. CAH gets press because one of its effects can be ambiguous genitalia, sometimes aka "intersex", but its effects on aldosterone (one of the steroids your body produces) can lead to dehydration, hyponatremia, hyperkalemia, metabolic acidosis and death, in infancy. "Ambiguous" is also used, erm, ambiguously; it doesn't only mean "large clitoris", it also includes things like the urethra and vagina opening into a common cavity and causing severe urinary tract problems.

If there is sufficient reason to believe that prenatal dexamethasone can keep children whose genes prevent them from producing 21-hydroxylase alive, or make it possible for them to avoid difficult, expensive and painful surgery to restore urinary function, that is a valid avenue for research conducted under the auspices of an institutional review board. Attempting to tweak girls' personalities to make them more girly is way, way out of bounds, and New and Nimkarn should be censured for even suggesting the idea.

But what I really want to talk about is steroids, and what you, dear reader, do and don't already know about them.

"Steroid" is a really, really broad term. It's as broad as "sugar" or "alcohol". (The categories also overlap, which can be confusing; there are sugar alcohols and steroid alcohols.) When you think of "sugar" you probably think of that grainy white stuff you put in your coffee, and when you think of alcohol you probably think of booze -- but the picture is actually much bigger. All monosaccharides and disaccharides are sugars, including the ribose and deoxyribose that form the backbone of your RNA and DNA. Ethanol is the alcohol we drink, but it's just one of the aliphatic alcohols, which also include isopropanol (rubbing alcohol), methanol (can blind or kill you if you drink it!), xylitol (used to sweeten chewing gum), mannitol (baby laxative), ethylene glycol (antifreeze!), and glycerol (aka glycerin). I won't bore you with all the various non-aliphatic alcohol families, but there are a lot of them. So, also, with steroids.

Steroids are emphatically not just what dumb jocks inject to get really ripped really fast. (Those are certain anabolic steroids.) Just as "alcohol" refers to organic molecules with an -OH bound to a carbon atom and "sugar" refers to a particular type of carbohydrate building block, "steroid" specifically means "molecule with three six-carbon rings and one five-carbon ring in a particular arrangement". (That four-ring core is called a sterane, if you were curious.) And, wow, are there ever a lot of them. Cholesterol is a steroid. So are androgens (including testosterone), estrogens (there's more than one), and progestagens (humans only have the one, progesterone). But unless you're on hormonal birth control, taking estrogen or testosterone replacements, taking progesterone as part of fertility treatment, or otherwise tweaking your own sex hormones, if your doctor prescribes you a "steroid" it is almost certainly going to be one of the corticosteroids.

Dexamethasone is, as I said above, a glucocorticoid -- a member of the family of corticosteroids that can affect immune function. (In the interest of space, I'm going to skip the other family, the mineralocorticoids.) It is, not to put too fine a point on it, the nuclear option of corticosteroids. Long-term use -- which, for glucocorticoids, means more than a week -- causes the adrenal glands to start shutting down; stopping glucocorticoids abruptly after this has happened can cause an Addisonian crisis, which can be fatal. Even long-term use as directed frequently causes Cushing's syndrome, which has a whole raft of nasty symptoms including rapid weight gain, high blood pressure, insulin resistance, severe anxiety, and psychosis. As if that weren't enough already, long-term use also causes osteopenia, a lowering of bone density that is the precursor to osteoporosis.

Given the degree of side effects involved with long-term dexamethasone usage -- and the several weeks of treatment involved in the New and Nimkarn study constitutes "long-term" -- the "behavioral masculinization" paper rolls over from "horrible" to "sheer, unrestrained evil". They are literally advocating putting pregnant women through multiple weeks of chemical torture -- not to save lives, but in pursuit of a behavioral "ideal".

If you think this is anything even remotely resembling right, I invite you to spend a month on dexamethasone -- without medication to mitigate side effects, remember we can't give benzos to pregnant mothers because they might adversely affect the fetus! -- and find out what it does to you. The stretch marks alone -- which look more like "I lost a fight with a cage full of tigers" than "boo, cellulite" -- will last a lifetime; the psychological damage from finding out just how deep your capacity for violence and self-hatred can run may fade, eventually.

All that said, there is one extremely valid prenatal use for dexamethasone. If you're about to give birth to a premature baby younger than 34 weeks, one injection of dexamethasone 24-48 hours prior to birth will help the baby's lungs produce the surfactant which it needs to be able to breathe. (Multiple doses used to be the standard, but -- big surprise -- it turns out that the beneficial effects of multiple doses are no higher, in any statistically significant sense, than of a single dose, and the adverse effects on both mother and fetus with multiple doses are worse.) Consider the difference, though: one injection versus several weeks of dosing, sharp increase in likelihood of survival versus reinforcing social norms. It's like day and night.

What it all comes down to, in the end, is this: be an informed patient. Ask questions. When you're prescribed a medication, the minimum you need to know is:
  1. What exact medication is this? Don't accept a category as an answer. You wouldn't hire a contractor who told you she was going to build your cabinets out of "wood"; you wouldn't hire a florist who told you he would make your anniversary bouquet out of "plants".
  2. How long will you be on it?
  3. What is the intended benefit of taking this medication?
  4. What are the potential or likely adverse effects for the timeframe in which you'll be on it?
  5. (if applicable) What are the potential interactions with any other prescription medications, over-the-counter medications, supplements, herbs, &c you take?

Doctors have a lot of training, and they do learn how to perform risk analysis, but at the end of the day, you are the one who gets to decide whether the potential benefits of any medication are worth the risks involved. You can't know the benefits or the risks unless you know exactly what you're putting in your body. Ask, and don't put up with bullshit non-answers.


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September 2010

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