Rhonda: Yeah. Another sort of, I think, research gap is the sex differences. And it's definitely of interest to many, many women of all stages of life. So acknowledging the research gaps, I'm still gonna ask you some opinions to see if there are any. I know there's also, I think, some misconceptions in the general audience, with the general population also. So it'd be nice to kind of even touch on some of those.

One being, postmenopausal women, is HIIT good or bad for postmenopausal women? On the bad side, some women are worried about raising cortisol too high. Do you have any thoughts on doing HIIT for postmenopausal women?

Dr. Gibala: So specifically on the cortisol level, and again, I think the latest systematic reviews, meta-analyses, the studies vary a little bit, but by and large, I don't think individuals need to worry about chronic increases in cortisol levels systemically that are gonna cause them damage.

Clearly, cortisol levels can go up, just like catecholamines go up acutely during exercise. But I think there's some evidence now that would suggest that actually, in individuals that practice interval training, basal cortisol levels actually stay lower than prior to baseline. So I don't think it needs to be a major concern, especially given a lot of the other benefits that we can see with this type of approach. So that's on the cortisol issue specifically.

Rhonda: Yeah, and that, I mean, given all the benefits we've talked about, the cardiorespiratory, the muscle, skeletal muscle, the brain, I mean, it's pretty clear to me that, I mean, it'd be a hard sell to say, oh no, it's not beneficial for postmenopausal women. I hate, you know.

Dr. Gibala: And very different is, you know, individuals with PCOS, polycystic ovarian cancer, is there's ongoing work, some really good work out of Norway looking specifically at HIIT in individuals with that condition, showing some real benefits there. On the sex-based differences, you know, writ large, are there sex-based differences in some outcomes?

Yes, I think they're subtle. At least the evidence to this point would suggest there are some differences, they're probably subtle differences, but we do need to know a lot more. You know, are there massive differences between, for example, phases of the menstrual cycle or oral contraceptive users versus naturally cycling females?

Again, maybe some, but probably pretty subtle. So that doesn't mean they're not important, but I think the differences are likely small in most outcomes. But absolutely, we just, you know, need more research. We need more research on diversity of responsiveness, writ large, not necessarily even just biological males and females, you know, and you've talked about this on other episodes. You know, it's an active area of research and it's a frustrating area of research sometimes, so I'll give you a very specific example. Some of our research right now is looking at the mechanisms for the increase in VO2 max with very short sprint-type interval training, right? And so we know that that increases VO2 max, but we're not sure why.

And actually some of the work would suggest maybe it's more the muscle adaptations than we thought about or at least the cardiac output changes take a while. So I have a PhD student immersed in this area and his first study, we show that VO2 max goes up, stroke volume was up, cardiac output was up after 12 weeks of training, and it looked like there were some differences between the males and female participants in the study.

So we did a secondary analysis, wasn't appropriately powered, and we thought, yeah, actually it doesn't look like the women are responding very much, or the females, and the males are. So then we repeat the whole study using more best practice procedures, properly controlling for menstrual cycle phase and properly expressing fitness per fat-free mass.

And we were basically unable to replicate the original findings, and we certainly didn't see any evidence of a sex-based difference, which tells me something that we've hand-waved around a little bit around our conversation at this point, there's tremendous inter-individual variation in responsiveness.

And so at least right now, to my mind, in terms of potential differences in responsiveness, to specifically sprint-type training, it might be less about a male or female biology issue, and it might just be there's tremendous variability between individuals. And in the almost 40 participants in the combined two studies, it happened to be men, or people identified as males that responded to a greater extent, but it might not have anything to do with biological sex.

And I think that's where a lot, many areas are right now, not all of them, some there's very clear differences, but I think that's where the exercise field is writ large. And the vast majority of studies have not incorporated these best practices for making systematic comparisons between sexes.

Rhonda: Right, yeah. And also I think differences in, at least for me, it's like there's environmental, how much sleep do I get? Things that'll also affect my ability to perform, and things like that. So yeah, I mean, there's a lot of gaps in the field, and with respect to women and menstrual cycle, that's also a question I get a lot.

And I think the reality of it is that 20 to 30% of menstruating women are, during their menstruation are iron deficient, and they just don't even know about it. They don't even know about it, they're not thinking about it, they're not increasing their dietary intake of iron, they're not supplementing with iron during that period.

And maybe that alone also would affect some, I mean, iron's important for heme, right? And that's-

Dr. Gibala: I don't know the others, and if you talk to these female athletes, they're like, even if there is, I don't get to pick when my race date is. I know I have to peak for this day in four months time, you know, in this location.

Maybe you can structure your training around menstrual cycle a little bit, but I think that's just the reality, obviously, for women who compete in sport. And so, yes, we need to know if there's some differences there, but in the big picture, it doesn't really matter. It's just one more thing that potentially contributes to variability and responsiveness on the day, and you try and control all the other things as well as you can, you know, to peak as best you can on the day of your event, or your key event.