COGS 1st International Meeting (2020): Talks

Measuring Sex, Gender, and Sexual Orientation to Study Stress Physiology

Robert-Paul Juster (Université de Montréal)
January 8, 2020

It’s a real honour to be here, and I apologize for my voice, I’m at the end of a flu and a bad head cold. So, to use an old saying “every cell is sexed, every person is gendered, and every organism is stressed”. But what is stress? A very nice definition by Bruce McEwen is “stress is broadly defined as a real or interpreted threat to an individual’s physiological or psychological integrity, that results in biological and behavioral responses”.

We study stress in three different types of ways; looking at stress with psychological questionaries, looking at stressors, such as environmental stressors, and looking at stress responses by looking at objective biological markers. One that I’m very interested is cortisol; a stress hormone that is involved in the fight or flight response, or potentially the tend and befriend response.

One way that we can look at cortisol is by simply stressing people out. I spent the better part of my career stressing people out and collecting their spit. One thing that’s really interesting, is that men generally respond stronger in terms of cortisol production, compared to women. There is some evidence that women actually are more sensitive to social rejection, in terms of cortisol. So, we’re talking potentially of some gender effects already.

Another way is to look at cortisol responses throughout the day. Diurnal cortisol shows peak cortisol levels in the morning, and levels go at their lowest right before going to bed. Generally, we don’t find too many differences between men and women, except after about 45 minutes after waking up, women tend to show higher levels of cortisol than men.

Cortisol is only one player, however, and a lot of these different biomarkers are getting dysregulated together. This is the concept of allostatic load, which is the wear-and tear of chronic stress, and unhealthy behaviors. You can think of it really as the straw that breaks the camel’s back. Another way to think of it is that it’s a domino effect; cortisol, adrenaline, allostatic load, they’re all going to get dysregulated together, and that’s going to lead to a lot of changes and a lot of the traditionally used biomedical changes. And together when all of these get dysregulated, they are going to lead to disease, and death.

Allostatic load can be indexed with the number of biomarkers that are dysregulated in an array. So, you take a sample, you look at the biomarkers. In looking at allostatic load, there are very important differences across age. As you get older, you have higher allostatic load. To date, sex differences are really inconsistent. When I looked at the literature, a lot of the variables that kept coming out, really seemed to be gendered. So, women going to church, social supports, and so on. This got me very interested in looking at sex and gender perspectives.

And then there’s controversy with regards to the genderbread man representation, but I like the idea of just emphasizing the different dimensions. And this was something I got really interested in looking at during my PhD; to look at how stress hormones, gender roles, and sexual orientation would be related to cortisol and allostatic load.

So, first for sex hormones, I mentioned that men show higher cortisol, women taking contraception show lower cortisol, women in luteal phase show highest cortisol, and the for diurnal cortisol, there’s no real difference between sexes. All of these studies are assuming sex hormone variation but are not actually measuring sex hormones. So, in one study, I wanted to look at sex hormones. Here’s the typical profile, with men are showing higher cortisol than women but when we adjust for testosterone, estradiol, and progesterone for both sexes, we lose the sex effect, but we unmask the diurnal effect, where women show higher levels of cortisol, and this is actually driven by higher levels of testosterone.

Next, with gender roles, I like to use the BEM sexual inventory, and BEM proposed that people who have high masculinity or high femininity would be very adaptive. Those who score lower than the medium for femininity and masculinity, were considered undifferentiated, and were considered to be potentially, unhealthy. What I found in the study of 204 workers, was that androgynous individuals show higher self-esteem, higher well-being, and less depression. But interestingly, looking at allostatic load, I calculated it the way it’s normally done, using the individual biomarkers for a sample, but I also used sex specific cut-off’s, because for an array of 10-15 biomarkers, 10 of them were different between men and women.

So, for the one that doesn’t take sex into account, men showed higher allostatic load than women. But when I look at a sex-specific investigation, androgynous men show lower levels of allostatic load, than undifferentiated men, and undifferentiated men show higher levels of allostatic load, compared to undifferentiated women. Interestingly, no differences among women. And this is something that’s going to come out in some of my future research in sexual orientation, that I think some of the ways that we’re measuring gender, are not taking into account these biological differences.

Some future work that I’m doing now is I’m really interested at looking at sex composition, and occupational gender roles in relation to individual gender roles, and seeing if there are interactions, and how that might be stressful.

And finally, for sexual orientation, I measured it in a sample of 87 Montrealer’s, looking at three different ways. So, people had responded to advertisements, open-ended responses, and on a Kinsey scale. And what we found for stress reactivity when we exposed people to a Trier Social Stress Test, and we found that lesbian and bisexual women had higher levels of cortisol 40 minutes after being exposed to the stressor, compared to heterosexual women. And interestingly for men, gay and bisexual men, showed a flatline response. This is something we often see in the PTSD literature and fatigue literature, but we have a lot of other measures to complement our understanding. In terms of diurnal cortisol, we found no differences by sexual orientation, except those that had completely come out of the closet had lower levels of cortisol than those who hadn’t. In terms of mental health, surprisingly we found that gay and bisexual men actually had lower depression than heterosexual men, but that had actually been driven by those who had come out of the closet. If you had come out of the closet completely, you had less anxiety, less depression, and less burnout.

Next, for allostatic load, we had 20 different biomarkers. We found that gay and bisexual men had lower allostatic load than heterosexual men. This was actually driven by triglycerides, body mass index, and interlukin-6. There is literature that suggests that men are metabolically more fit, pay better attention to their diet, but this is something that we need to look at with health behaviors that we did not measure in this study.

This could be a selection bias as well, as these are people coming from Montreal. So, as part of my postdoc, I had the chance of working with people from UCLA with a sample of 14 thousand Americans. And interestingly we found that bisexual men had the highest allostatic load, while gay men had the lowest. And just to point your attention here, there were no differences here between women, and again we’re finding the same thing in this study, where we found no differences in allostatic load among women. So, this is really important for research looking at sexual orientation. We can’t just clump together LGBT, there are very important sex differences going on.

Future work that I’m looking at, is looking at structural stigma with Mark Hatzenbuehler. We’re interested in looking at where you lived in the United States, what are the laws that protect you, and what is your allostatic load. So, this is just another sort of way of measuring stigma at a more macro level.

Really, the importance of looking at stigma, which is really something we haven’t done in these previous studies, we’re assuming differences in psychosocial experiences, but we’re not actually taking them into account. So, it’s going to be really important in future research to look at variables of stigma, and health behaviors, and other resilience factors.

And finally, I just want to point out some research with a collaborator from the university of Oregon, looking at transgender men. This was a mixed design study where we looked at individuals who had high levels of stress with regards to transitioning, high levels of stress with coming out, and high levels of stress with regards to gender neutral bathrooms. All had high levels of cortisol. But, when we looked at perceived stress, which is a standard questionnaire, we didn’t find a difference. So, it’s really important to find psychosocial variables that are pertinent to the transgender community. And this is some work that I’m hoping to do as a young investigator.

And just to really point out the importance of looking at all of these different identities, and what’s unique about this work is that I’m trying to bring out all of the biomarkers, to try and understand how stigma gets under the skin and the skull. And also, resilience is extremely important, specifically, why would it be that gay men aren’t showing lower allostatic load, when bisexual men are showing higher? Bisexual men are a minority within a minority, that don’t garner the same social supports as gay men. Why are lesbian women not necessarily showing differences in allostatic load? That’s something that also needs to be explored.

With that, I’d just like to point that the real take home message of this work is that sex as a binary variable is simply insufficient in stress research. We need to be going towards more dimensional approaches. And in closing, it takes a village to do this work, so I’d like to thank all of the people who have been involved in this work, and thank you all for your attention.

Supporting Organizations

Women's Brain Health Initiative logo and website link Women's Health Research Cluster logo and website link Ontario Brain Institute logo and website link Women's Health Research Institute at BC Women's logo and website link Libin Cardiovascular Institute of Alberta logo and website link Canadian Institutes of Health Research logo and website link Women and Children's Health Research Institute logo and website link Elsevier logo and website link Centre for Gender and Sexual Health Equity logo and website Linköping University logo and website link Heart Stroke logo and website link centreDeRecherche logo and website link UMontreal logo and website link Einstein lab logo and website link