Hormones Impact Drug Metabolism

Metabolic differences between men and women aren’t limited to enzymes. Women also process drugs differently during different phases of their menstrual cycles.
This means that serum levels of vital drugs like Dilantin (phenytoin), a powerful anticonvulsant seizure medication, can dip dangerously low on certain days of the month. Women often have breakthrough seizures during times of hormonal fluctuation, sometimes resulting in serious physical injuries from falls or automobile accidents.
Drug-related QT interval prolongation is also affected by the menstrual cycle. At certain points of the cycle, some drugs have been shown to cause a greater increase in the length of the QT interval. If a premenopausal patient is on multiple QT-prolonging drugs, she could therefore be at far greater risk of asystole or other cardiac events during certain days of her cycle.
While it’s clear that women’s menstrual cycles do have a measurable and potentially damaging impact on drug metabolism, there are few guidelines or even suggestions to help prescribers address this. While there is information out there about how certain classes of medication (some HIV meds, antiseizure meds, antidepressants, benzodiazepines, and one class of antibiotics) might render birth control less effective, I have not found any alternate dosing formulas to balance those few days when serum levels are impacted by hormone spikes or drops. Often, the possibility of premenstrual breakthrough incidents or QT prolongation isn’t even discussed when the drug is prescribed—and these potential complications are rarely, if ever, considered in an emergency setting. Women are taken completely by surprise.
The flip side of this discussion is how hormones themselves are affected by drugs—particularly when prescribed hormones, like birth control pills, are in use.
A woman came into the ED recently with a case of “vaginal bleeding and anxiety” (according to her triage assessment). Of course, whenever I hear “anxiety” coupled with a female issue my ears perk up. There was more to this story, I knew.
Turns out, the woman, whose name was Saira, had Turns out, the woman, whose name was Saira, had gone to her doctor several months ago because of recurring migraine headaches. She was prescribed topiramate, which is effective for migraines but also interferes with the efficacy of oral birth control. Her prescriber did not mention this to her.
A month later, Saira was pregnant. She and her husband decided that they were not in a position—financially or otherwise—to expand their family, so she went to her local clinic and received medication to assist with an abortion. After suffering through several days of heavy bleeding and intense cramping, she thought the worst was over—until, about four weeks later, when the intense cramps and vaginal bleeding started again.
Saira didn’t have “anxiety.” She was in pain and scared. After I ordered an ultrasound, it was clear that she needed an emergency dilatation and curettage (D&C) to remove what we call “retained products of conception.” Had she not come to the ED, she might have suffered serious effects—including systemic infection, hemorrhage, or even the loss of the ability to bear children in the future.
Saira lost several days of work because of her symptoms. She had to be admitted to the hospital for the D&C, as it had to be conducted under general anesthesia (which carries its own risks); this meant more time out of work and finding care for her other three children so that her husband didn’t lose days of necessary income as well.
All these layers of risk and impact—to her health, her family, and her financial situation—could have been avoided if Saira’s provider had simply informed her that her migraine medication would impact her birth control. To me, this is just another indication that we need to place greater value on women’s reproductive rights across the board in medicine. Since 17 percent of women of reproductive age in the United States are currently using oral birth control (versus only 10 percent using condoms),6 it’s imperative that we both understand and share with women how certain drugs can affect the efficacy of birth control and vice versa—how birth control can affect the performance of other drugs.
We’ll talk more about pharmaceutical hormones in Chapter 7, but for now, it’s important to know that the ways in which drugs—including hormones—combine in a woman’s body can produce complications that don’t have any equivalents in the male model.


Jo Jones et al., “Current Contraceptive Use in the United States, 2006–2010, and Changes in Patterns of Use Since 1995,” National Health

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