Study weighs up impact of different drug dosages for men and women

Men and women experience disease differently, including how they develop, the length and severity of symptoms, and the effectiveness of treatment options.
 
The same concept applies to treatment, with many men and women often responding differently to the same prescribed medication.
 
In fact, women are up to 75% more likely to experience adverse reactions to prescription drugs compared to men, according to a newly published study from Australian National University (ANU).
 
A range of differences in traits between males and females were identified in the study, partly debunking previous theories that adverse reactions were mainly due to differences in body weight, and validating the authors’ calls that this should be considered when prescribing medicines for treating diseases.
 
The researchers used mice as a ‘pre-clinical’ disease model to analyse more than two million data points, capturing over 300 unique traits.
 
Prior to the study, lead author Dr Laura Wilson said it had been assumed that the results from such ‘pre-clinical’ trials would apply equally to males and females, but the results revealed otherwise.
 
‘It is clear females aren’t just smaller versions of males – meaning drug reactions are unlikely to be alleviated by simply adjusting the dosage for body weight,’ she said.
 
‘Our analyses showed sex differences in many traits that cannot be explained by body weight. For example, iron levels and body temperature, morphology traits such as stored fat, and heart rate variability.
 
‘Most biomedical research has been conducted on male cells or male animals. It has been assumed any results will apply to females as well … but we know men and women experience disease differently.’
 
RACGP President Dr Nicole Higgins says the study is a reminder of the importance of targeted health interventions – especially as previous research shows that women often cite adverse drug reactions as a reason for discontinuing medications, while they can also lead to longer related hospitalisations.
 
‘Men and women are different and experience diseases differently, so we can’t just study male anatomy and hope that everything will be equal for women,’ she said.
 
‘Instead, we need to ensure that a more balanced and inclusive approach is adopted.’
 
Dr Higgins’ call for a new approach comes in the wake of a Federal Government decision to establish a National Women’s Health Advisory Council, for which she is special adviser to Chair Ged Kearney, Assistant Federal Health and Aged Care Minister.
 
‘The timing of this study is opportune,’ Dr Higgins said. ‘In this role [of special adviser to the Council], I plan to draw attention to research such as this ANU study and make sure that women’s healthcare is front of mind for researchers and politicians.
 
‘I look forward to driving change in women’s healthcare in Australia and ensuring that action is taken to improve health outcomes for all women.’
 
As part of the ANU research, the team quantified sex differences in the ‘allometric relationship’  between trait value and body weight for 363 phenotypic traits in male and female mice, finding that body weight differences did not explain all sex differences in trait values, but scaling by weight ‘may be useful’ for some traits.
 
‘Our results show sex differences in phenotypic traits are trait-specific, promoting case-specific approaches to drug dosage scaled by body weight in mice,’ the authors wrote.
 
The researchers say as much less is known about how women experience disease, further consideration of sex differences for drug dosing on a case-by-case basis is needed.
 
Dr Wilson noted that as a result of the two sexes experiencing disease differently, women are ‘often worse off’.
 
For example, with cardiac symptoms men may more commonly experience crushing chest pain – seen as a primary symptom of heart attack – whereas this is a much less common symptom for women, who are more likely to experience intense nausea.
 
‘Our study could help clarify the nature of the differences in responses to certain drugs and provide a path forward to reducing drug reactions,’ Dr Wilson said.
 
Additionally, making decisions for women’s healthcare based on research conducted on men – and vice-versa – has ‘potentially profound’ clinical and economic consequences, particularly in relation to adverse drug reactions, according to the researchers.
 
Linking back to the National Women’s Health Advisory Council, which is part of the National Women’s Health Strategy 2020–30, Dr Higgins said the study is a clear example of the need for targeted healthcare.
 
‘As Dr Wilson warns, women are not just smaller versions of men, and we can’t forget that,’ she said.
 
‘We must address inequalities in healthcare and that includes the treatment and care of women and girls and the research that underlies that care.’
 
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