Compared to men, we know much less about how women experience the disease.
Biomedical research helps us understand the timeline of diseases and how we can treat them. In the past, most of it was carried out in male cells and experimental animals, such as mice. It has been assumed that the results of such “preclinical” investigations in men also apply to women.
However, men and women experience the disease differently. That includes how diseases develop, the duration and severity of symptoms, and the effectiveness of treatment options.
Although these differences are now widely recognizedare not fully understood. And women are often worse off as a result.
This is the case with prescription drugs. Women experience around 50-75% more adverse reactions than men. This results in many drugs being withdrawn from the market due to concerns about the risks to women’s health.
Therefore, it is believed that if drug doses are adjusted according to body weight, women will often receive lower doses than now, which may alleviate adverse reactions.
But that may not be the case.
in new research published today in Nature Communicationswe show that this basic assumption in biomedicine, that women are “smaller versions” of men, is not supported by most preclinical traits (things like glucose levels, for example).
Therefore, drug reactions in women are unlikely to be alleviated simply by adjusting the dose to body weight.
Adverse drug reactions are common and costly for healthcare
Basing women’s health decisions on research done on men, and vice versa, has potentially profound consequences. In the case of adverse drug reactions, the impacts are significant from both a clinical and economic point of view.
A recent study estimated that 250,000 hospital admissions in Australia each year are drug-related, costing the health care system around $1.4 billion annually.
Medication reactions have also been shown to lengthen hospital stays. in a large UK studypatients admitted to hospital with an adverse drug reaction stayed a median of eight days.
Women often cite adverse reactions as the reason for discontinuing medications. If weight-adjusted drug dosing could reduce adverse drug reactions, we would see that women would receive greater potential benefit from the health care system.
The weight of the evidence
But what evidence do we have that weight adjustment will work? The US Food and Drug Administration (FDA) has already recommended dosage changes for some medications for women (such as zolpidem sleeping medication). Additionally, weight-adjusted dosing for some antifungal medications Y antihypertensive drugs seems to work.
On the other hand, drug reactions are strongly related to what the drug does in women’s bodies , and less in men. there’s also many documented differences in physiology between men and women that are related to the way the body absorbs and eliminates drugs, and not to body weight.
To get to the bottom of this, a large-scale approach is needed. We borrow a method routinely used in evolutionary biology, known as “allometry”, which examines a relationship between a trait of interest and body size on a logarithmic scale.
We applied allometry analysis to 363 preclinical traits in men and women, comprising more than two million data points from the International Mouse Phenotyping Consortium.
We focus on one of the most common disease model animals: mice. We asked whether sex differences in preclinical traits, such as fat mass, glucose, LDL cholesterol, could be explained by body weight alone.
Our analyzes recovered sex differences in many traits that cannot be explained by differences in body weight. Some examples are physiological traits, such as iron levels and body temperature, morphological traits, such as lean mass and fat mass, and cardiac traits, such as heart rate variability.
We found that the relationship between a trait and body weight varied considerably across all the traits we examined, meaning that the differences between males and females could not be generalized: females were not simply smaller versions of males.
Ignoring these differences in some cases, such as measures of blood cells, bones, and organs, could result in missing a large part of the population variation for a particular trait: up to 32% for women and men. 46% for men.
This complexity means that we must consider gender differences for drug dosing on a case-by-case basis.
One size does not fit all
In an era where personalized medicine interventions are within reach and patient-specific solutions are on the horizon, we now know that data based on sex is badly needed promote care equitably and effectively.
Our study uncovers the ways in which men and women may vary in many preclinical traits, indicating that biomedical research needs to focus more on measuring how and in what ways the sexes differ.
In particular, when a relationship between gender and drug dose is discovered, our data suggest that the dose response is likely to be different for men and women.
The methods of our study could help to clarify the nature of these differences and provide a way forward to reduce drug reactions.