What is the difference between Sex and Gender and why does it matter in how medicines work?
According to the World Health Organization, sex refers to the biological and physiological characteristics that define men and women. Gender refers to the socially constructed roles, behaviors, activities, and attributes that a given society considers appropriate for men and women. In simpler words, sex is assigned at birth. And gender is how a person identifies themselves.
So, why does it make a difference in the medical world? The terms sex and gender appear to be used interchangeably. But if we want to be truly inclusive as a society, ignoring the difference between the two is not right, socially or scientifically and especially not, when it comes to medication response. Why does it matter to take the distinction between sex and gender in treatment response? Let's consider a case where a transgender individual is on hormone therapy (ie. they are on exogenous testosterone or exogenous estrogen as part of the process to align secondary sex characteristics with gender identity). Now, we know that (cisgender) women experience more adverse events (or 'bad side effects from a medicine') than men do. It is due to various reasons that I will go into detail in future posts, but globally, 60% of women reported more side effects than men did (Source: WHO Vigibase). However, we have no data on adverse events of medication on transgender adults. It is dangerous because we don't have evidence that a certain dose of medicine will produce a certain effect in these individuals, therefore, most of the time, the medication decision is based on cisgender (or 'sex-based) status, which could have dangerous outcomes.
Why is that? Well, a part of the reason why women experience drug effects differently than men is due to the fact that hormones impact drug metabolism. For example, estrogens are metabolized by many of the same enzymes that break down ('metabolize') many of the medicines that we take. Considering that a transgender individual would have endogeneous estrogen along with taking exogenous estrogen unless we know the exact level of the drug in the body, we don't know how the level of exogenous and endogenous hormones would affect the enzymes involved in drug metabolism and it is all guess-work till then. One of these enzymes, called Cytochrome P450 A12 or 'CYPA12' activity may be lower in transgender adults undergoing estrogen treatment. Because CYP1A2 metabolizes several medications that may be taken by transgender adults (e.g., duloxetine and olanzapine), we should characterize CYP1A2 activity in transgender adults before and during hormone therapy.
One of the main principles of the US 'Sustainable Development Goals' or UNSDGis to 'leave no one behind.' If we were to truly follow that, we should make sure that studying how effective or safe medication is involves the difference between sex and gender, and adequate reporting is mandated so that whether it is biological sex or gender identity, nobody ever suffers from medication errors.