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QUESTION: I’m interested in knowing whether women ever respond differently than men to prescription drugs. Do they?
ANSWER: The short answer to your question is yes, in some cases. But it’s taken the medical community a long time to reach that conclusion.
Traditionally, it was believed that men and women react to medications in the same way. In fact, most research studies are carried out mainly on men. Even preliminary animal studies primarily use male rodents.
In some respects, the practice of excluding women from drug trials could be considered “well meaning,” says Dr. Cara Tannenbaum, scientific director of the Institute of Gender and Health at the Canadian Institutes of Health Research in Montreal.
If a woman became pregnant during a study, her unborn child might be put at risk of birth defects. Many researchers were also striving for clear findings and they mistakenly believed that female hormonal fluctuations might complicate their results.
In recent years, however, there has been a growing awareness that women may not always respond in a similar fashion as men to certain drugs, says Tannenbaum.
A key turning point occurred in January 2013, when the U.S. Food and Drug Administration (FDA) issued new dosage recommendations for the commonly used sleeping medication zolpidem, sold under the brand names of Ambien and Sublinox. (Health Canada took similar action a year later.)
The federal regulators said the dose prescribed to women should be cut in half, after a series of studies revealed that women metabolize, or break down, the drug more slowly than men. Women could wake up with high levels of the drug still in their bloodstream, which might impair their ability to drive or do other tasks requiring an alert mind.
This was the first time that regulators recommended sex-based dosages for an oral medication.
Since then, the FDA and Health Canada have called on researchers to include more women in clinical trials.
There are certainly good biological reasons to think that women and men may handle some medications differently, says Dr. David Juurlink, a drug-safety expert and head of Clinical Pharmacology and Toxicology at Sunnybrook Health Sciences Centre.
He notes that drugs have to be absorbed, metabolized and eventually eliminated from the body – processes that involve several different organs. There can be subtle differences in how these organs function depending on a person’s sex.
For instance, the activity levels of enzymes that metabolize drugs in the liver can sometimes differ in men and women, says Juurlink. Furthermore, women tend to have a higher percentage of body fat than men, and certain drugs can accumulate in fat tissue. That means some drugs are more likely to build up in the bodies of women than men.
Aside from biology, the medical profession also treats the sexes differently. “Women are more often prescribed medications such as sedatives, sleeping pills, opioids and antidepressants,” says Tannenbaum. The fact that women take more medications than men increases their chance of suffering from drug interactions and side effects.
A study conducted by the U.S. Government Accounting Office suggests that women do indeed face elevated risks from some medications. Between 1997 and 2000, the FDA pulled a total of 10 drugs from the market for safety reasons. A data review by the accounting office found that eight of the withdrawn drugs “posed greater health risks for women than for men.”
These problems might have been avoided if more females had been included in the research – starting with the basic science involving laboratory animals.
In a groundbreaking study published last year, a team of Canadian and U.S. researchers revealed that pain is processed in male and female mice using different cells. Earlier work, done exclusively on male rodents, concluded that the transmission of pain signals in the spinal cord depends on an immune cell called microglia. But when the researchers did the same experiments using female mice, they discovered that another type of immune cell – called a T-cell – appears to be responsible for sending the pain signals.
“My expectation was that there was going to be no difference between the male and female mice,” says one of the authors of the study, Dr. Michael Salter, Chief of Research at the Hospital for Sick Children in Toronto. But, prodded by one of his team members – Dr. Jeffrey Mogil of McGill University in Montreal – they decided to test female rodents. “It was purely curiosity driven. I think the result caught people by surprise – including me,” says Salter.
Their findings could have far-reaching implications, suggesting that pain medications may need to be focused on different mechanisms in men and women, Salter says.
Despite these recent insights, males still appear to be the most common test subjects – even for drugs intended for women.
Take the case of Addyi, the first drug approved to treat low sexual desire in women.
Leading up to its approval last year, the drug maker did a study on 23 male and two female volunteers to determine what happens when Addyi is taken with alcohol. The study concluded that mixing the drug with alcohol increases the risk of adverse side effects such as fainting, dizziness and low-blood pressure. Yet those findings may have actually understated the risks because so few women were included in the study, says Juurlink. After all, it’s well known that women have a stronger reaction to alcohol than men – and might be expected to experience more side effects when combined with the drug.
“This is a drug specifically marketed to women, but the safety data is based on a study done in men,” says Juurlink. “That makes no sense.”
In an effort to redress the research imbalance, CIHR’s Institute of Gender and Health has started awarding grants to encourage scientists to add female rodents into their lab experiments.
“We are building a group of researchers who are interested in exploring sex and gender issues,” says Tannenbaum. “We have a way to go, but at least it’s now on people’s radar.”
So, in the meantime, should women be concerned every single time they pop a pill? Not necessarily.
Doctors still expect that women and men will have the same response to most drugs. But for a select group of medications, the differences could be significant.
The best way to identify those drugs is by routinely including women in research. As Salter puts it: “Unless you actually ask the question – Is there a difference? – you are never going to know the answer.”
Sunnybrook’s Patient Navigation Advisor, provides advice and answers questions from patients and their families. His blog, Personal Health Navigator, is reprinted on Healthy Debate with the kind permission of Sunnybrook Health Sciences Centre. Follow Paul on Twitter @epaultaylor.