For the video version of this post, click here. There are two elements you can expect to see in almost any study: the first is some effect size - a measure of association between an exposure and outcome. The second is a subgroup analysis - a report of how that effect size differs among different groups. Sex is an extremely common subgroup to analyze - lots of things differ between men and women. But a really unique study appearing in the Journal of the American College of Cardiology suggests that sex might not matter when it comes to coronary disease. What really matters is gender.
The study, with cumbersome acronym GENESIS-PRAXY, examined 273 women and 636 men of age less than 55 who were hospitalized with Acute Coronary Syndrome (ACS). Sex was based on self-report, and was binary (man or woman). But gender isn’t sex. Gender is a social construct that represents self-identity, societal roles, expectations and personality traits, and can be a continuum - think masculine and feminine.
The authors created a questionnaire that attempted to assign a value to gender. Basically, questions like - “how much of the child-rearing do you perform” or “are you the primary breadwinner for your household” - in other words these are based on traditional gender norms - but that’s as good a place to start as any. A score of 100 on the gender scale was “all feminine”, and a score of 0 “all masculine”. Most of the males in the study clustered on the masculine end of the spectrum, while the females were more diverse across the gender continuum.
What was striking is that the primary outcome - recurrence of acute coronary syndrome within a year, was the same regardless of sex - 3% in men and women. But a greater degree of “femininity” was significantly associated with a higher recurrence rate. Feminine people (be they male or female) had around a 5% recurrence rate compared to 2% of masculine people. This was true even after adjustment for sex, so we’re not simply looking at sex in a different way - gender is its own beast.
What does it all mean? Well, it shows us that our binary classification of sex may be too limited in the biomedical field. Of course, there will always be hard and quantifiable physiologic differences between men and women. But what is so cool is that it’s the more difficult to quantify gender-related differences that may matter most when it comes to health and disease.
Of course, this conclusion is way too big to be supported by one small study with a 3% event rate. But given the surprising and really interesting nature of the results, I’m sure we’ll have many more studies of this sort following close behind.
For the video version of this post, click here. Pre-exposure prophylaxis for HIV - PrEP - basically entails taking a medication, typically a combination pill of tenofovir and emtricitabine to reduce the risk of acquiring HIV. PrEP is highly efficacious, with several randomized trials demonstrating a sharp reduction in transmission rates when PrEP is used in high-risk populations. In fact, among men who have sex with men, you need to provide PrEP to about 12 people to prevent one HIV infection. That’s a very low number needed to treat for such a costly disease.
But efficacy isn’t the same as effectiveness. Efficacy is an ideal. Clinical trials follow their patients extremely closely, ensure they are taking their medication, and select their participants very carefully. Effectiveness is the real-world performance of a drug, and, until now, we haven’t had great data to see how PrEP would work in practice.
And there have been concerns. PrEP should be used with a condom, it doesn’t replace a condom. It can’t be taken immediately prior to risky sexual behavior - it’s a daily medication. There is a low, but real, risk of kidney dysfunction with the drug. But the real controversy surrounds a small but vocal group of physicians and AIDS activists who suggest that PrEP will ruin so-called “condom culture”, opening the door to less safe sex, increased sexually transmitted infections, and even an increase in HIV transmission rates.
That’s why this article, appearing in JAMA Internal Medicine is so important. The study followed 557 men who have sex with men and transgender women in three clinics across the US for about a year. All were HIV negative, but at increased risk of HIV infection, and all were provided PrEP free-of-charge.
Adherence was high - over 80% of individuals had therapeutic tenofovir levels when checked. Encouragingly, adherence was highest among those who engaged in the highest risk sexual behaviors. That’s right - our patients at risk understand they are at risk.
Over the course of the study, there were 2 new HIV infections, both in men with subtherapeutic levels of the drug. Based on baseline rates we would have expected around 11. But that impressive result is not what really matters in this study.
Rates of receptive anal sex without a condom didn’t change at all over the course of the study. Sexually transmitted infection rates didn’t change. In other words, the availability of a drug that can really prevent HIV transmission didn’t open some time portal to 1983. PrEP did not destroy condom culture, not that condom culture is all that pervasive. This is one of those situations where we have to respect the intelligence of our patients. Educate them clearly on how this medication is to be used, and trust that they, as consenting adults, will use the drug the right way.