Why is the FDA keeping women up at night?

The public health perils of overstating sex differences

American women can’t sleep. Over 1 in 4 have insomnia, and rates rise as women age. There are a range of effective treatments for insomnia - chief among them the drug zolpidem (better known as Ambien). Used correctly, zolpidem can help adults fall asleep and stay asleep, and there are over 40 million prescriptions written for zolpidem in the U.S. each year. But the recommended prescription dose for women is just half the dose of men.

The FDA argues that this is necessary because women have lower clearance levels of the drug than men and are more impaired by it, especially at the critical 8-hour mark (when people will awaken and begin their daily activities). In 2013, zolpidem became the first drug with FDA-mandated sex-specific dosing, a decision celebrated by women’s health advocates as a breakthrough acknowledgment of how sex differences in biology influence men and women’s health. In 2014, the NIH used the case of zolpidem as Exhibit A in arguing for their new, much-debated policy requiring study of sex differences in all preclinical research.

But as GenderSci Lab members Heather Shattuck-Heidorn and Sarah Richardson argue in an Op-Ed in today's Washington Post, the paradigmatic example for advocates of sex-based medicine is actually quite the opposite. Zolpidem, they argue, offers a cautionary tale for sex differences medicine of the dangers of neglecting interacting variables such as body size and composition, unvalidated extrapolation from animal models to human males and females, and failing to weigh the public health harms of overstating sex differences.

Highlighting a recent review of the science on sex differences and zolpidem by David Greenblatt, an expert on zolpidem pharmacokinetics and pharmacodynamics, Shattuck-Heidorn and Richardson argue that there actually “isn’t any scientific evidence supporting sex-based dosage for zolpidem.” And rather than increasing safety, underdosing harms women who need treatment for their sleep disorders and poses a public health risk when, for example, undertreated women drive while drowsy.

The implications, however, go further than the FDA sex-based dosage guidelines for zolpidem, which Shattuck-Heidorn and Richardson recommend reversing. “With NIH now requiring analysis of sex in all $30 billion of the medical research it funds each year,” they argue, “we need rigorous standards for documentation of clinically relevant sex differences, including accounting for intersecting variables like body size and composition. And while considering sex can be important in basic biology, sex difference studies in cells and rodents should not be applied to women without validation in human studies.”

Read the Op-Ed here: Focusing on differences between the sexes is leading medical researchers astray

Originally published at https://projects.iq.harvard.edu/gendersci/blog/why-fda-keeping-women-night-public-health-perils-overstating-sex-differences