Intersex Experts: Protect Pregnant Moms From Off-Label Drug

Report says doctors prescribe drug off-label to bypass study regulations.

ByABC News
August 21, 2012, 4:27 PM

Aug. 22, 2012— -- Janet Green was born with congenital adrenal hyperplasia, a condition that is one of 36 disorders of sexual development, leaving her with ambiguous genitalia, or intersex.

During the earliest weeks of conception in her mother's womb, Green was bathed in an overproduction of male hormones that caused a masculinization of her body and brain.

Girls with the condition can have clitorises as large as small penises or labia that look like a scrotum, but the internal sex organs are normal.

"I remember people being concerned about my body and a discomfort talking about it," Green, now a 55-year-old real estate agent from New York, said of her grueling medical journey. "I just wanted to be normal and fit in."

Standard treatment is surgery, which can be painful and leave psychological scars. But since the 1980s, doctors have prescribed a powerful steroid off-label for pregnant mothers who are at risk for the condition.

Now, in a report published this month in the Journal of Bioethical Inquiry, researchers call for more investigation into the use of that drug, dexamethasone, which they say is potentially unsafe.

The drug is approved by the Food and Drug Administration for the treatment of inflammation, certain forms of arthritis and some cancers.

But off-label, dexamethasone is used prenatally to reduce rates of typically boy-like chararteristics, lesbianism and bisexuality in girls, characteristics clinicians have termed "behavioral masculinization."

There are no requirements by the FDA for off-label use.

Only one in eight children conceived by at-risk parents ever gets any potential benefit from the drug, according to the report, and it has never been scientifically tested in controlled clinical trials.

"Women don't even know it's experimental," said Alice Dreger, lead author of the report and professor of clinical medical humanities and bioethics at Northwestern University in Chicago.

Just this year, a Swedish study on dexamethasone reported nearly 20 percent of the children exposed to the drug had a "serious adverse event," including anxiety and mood disorders and problems with memory and verbal processing.

"There is a lot of exposure with little benefit and a fair amount of risk," said Green, who is now a patient advocate as interim executive director of the Accord Alliance in Whitehouse Station, N.J. "To me, that's a scary thing.

"Over time, a lot of things have been done to girls that are experimental and this is another one."

Bioethicists have sounded the alarm because, they say, doctors are bypassing the strict regulations and ethical protocol of clinical trials by offering the drug off-label, then recruiting the same patients for federally funded follow-up studies.

Mothers were told the therapy was "safe for mother and child," she said, but there has been no scientific evidence. "Until we get decent studies we can't answer what are the side effects."

Many obstetrical textbooks describe it as a "standard of care," report author Dreger said.

The report, co-authored by Ellen Feder, associate professor of philosophy and religion at American University in Washington, D.C., and Anne Tamar-Mattis, executive director of Advocates for Informed Choice in Cotati, Calif., was based on clinician grant requests obtained under the Freedom of Information Act.

Dreger said doctors have expressed concern in the past decade about the off-label use of dexamethasone.

The drug has been routinely recommended by Dr. Maria New, a world-renowned expert on congenital adrenal hyperplasia and pediatric endocrinologist at Mt. Sinai Medical Center in New York City.

A 2010 investigation by the Department of Health and Human Services, Office for Human Research Protections on her studies of the off-label use of the drug concluded that there was "no evidence" of ethical violations.

"It is very common for medication for children to be prescribed off-label," she said. "The Food and Drug Administration has also issued a waiver in this case for an investigational new drug application. Thus, the charge of using an off-label drug for research purposes without proper oversight is unfounded."