Women are 50–75% more likely to have adverse drug reactions—a new mouse study finally helps explain why

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” research 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.

Smaller bodies?

Although these differences are now widely recognized, they are not fully understood. And women are often worse off as a result.

This is the case of 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 This results in many drugs being withdrawn from the market due to concerns about the risks to women’s health.

It has been argued that drug reactions in women are due to sex differences in body weight rather than differences in how the drug works in the body.

Therefore, it is thought that if drug dose are adjusted according to body weightwomen 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 females are “smaller versions” of males, is not supported by most preclinical traits (things like glucose levelsfor instance).

So, drug reactions in women it is unlikely to be relieved simply by adjusting the dose to body weight.

Adverse drug reactions are common and costly for healthcare

Basing women’s health care decisions on research done on men, and vice versa, has potentially profound consequences. In the case of Adverse drug reactionsthe impacts are significant from both a clinical and economic perspective.

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 a year.

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 quote 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 biologyknown as “allometry“, which examines the 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 sex 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 can vary in many preclinical traits, indicating that biomedical research it needs to focus more closely 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.

This article is republished from The conversation under a Creative Commons license. Read the Original article.