WEBVTT 00:00:00.000 --> 00:00:03.680 Simply having the regulations state that SRY 00:00:03.680 --> 00:00:06.320 is used as a proxy to determine if you have a 00:00:06.320 --> 00:00:08.160 Y chromosome or not. And that's their kind of 00:00:08.160 --> 00:00:10.119 their bottom line. If you have SRY, then you're 00:00:10.119 --> 00:00:11.619 going to have a Y chromosome and vice versa. 00:00:11.720 --> 00:00:14.419 But that's the part that's just not 100 % true 00:00:14.419 --> 00:00:17.239 because you can have or not have SRY. And that's 00:00:17.239 --> 00:00:19.820 irregardless of having a Y chromosome or not. 00:00:21.359 --> 00:00:24.100 Hi Shani, it's my pleasure to have you on Evidence 00:00:24.100 --> 00:00:27.280 Strong Show. for the second time. And please 00:00:27.280 --> 00:00:29.679 briefly introduce yourself. Yes, Alex. Thanks 00:00:29.679 --> 00:00:31.399 for having me. It's nice to talk to you again. 00:00:31.600 --> 00:00:34.560 So last time we talked about sex differences 00:00:34.560 --> 00:00:39.039 in exercise physiology. And so I introduced myself 00:00:39.039 --> 00:00:41.840 then, but I guess I'll say again that I'm a researcher 00:00:41.840 --> 00:00:45.060 in genetics and molecular biology and how it 00:00:45.060 --> 00:00:47.619 relates to sex differences, both in health and 00:00:47.619 --> 00:00:50.500 disease. And also in the past, I had a stronger 00:00:50.500 --> 00:00:53.420 focus in exercise physiology. And I'm an 800 00:00:53.420 --> 00:00:56.409 meter runner myself. I guess even more related 00:00:56.409 --> 00:00:59.729 to this topic. And yeah, I'm in Melbourne at 00:00:59.729 --> 00:01:02.149 the Hudson Institute doing a postdoc and finished 00:01:02.149 --> 00:01:06.849 my PhD in epigenetics about four years ago. Amazing. 00:01:06.930 --> 00:01:11.590 So today we talk about DSD athletes and transgender 00:01:11.590 --> 00:01:14.790 athletes and the policies and how they relate 00:01:14.790 --> 00:01:17.810 to research. So let's start with some kind of 00:01:17.810 --> 00:01:21.469 definitions, what DSD athlete is and transgender 00:01:21.469 --> 00:01:25.750 athlete and how they differ. talking about dsd 00:01:25.750 --> 00:01:29.510 and transgender i'll define sex and i'll define 00:01:29.510 --> 00:01:31.849 gender and i think that those are commonly used 00:01:31.849 --> 00:01:35.349 interchangeably in society but in biology there 00:01:35.349 --> 00:01:37.650 are two separate words with separate definitions 00:01:37.650 --> 00:01:41.750 so sex we call the biological sex and the two 00:01:41.750 --> 00:01:44.530 main categories are male and female and i'm keeping 00:01:44.530 --> 00:01:46.969 it simple for the sake of the definition and 00:01:46.969 --> 00:01:49.290 we'll go into more details after and this is 00:01:49.290 --> 00:01:53.959 determined by our sex chromosomes so Female typically 00:01:53.959 --> 00:01:58.120 will be XX and having XX chromosomes means you 00:01:58.120 --> 00:02:00.239 have a certain set of genes and those genes lead 00:02:00.239 --> 00:02:02.620 to development of ovaries. On the other hand, 00:02:02.620 --> 00:02:04.829 you have... XY individuals, that means they have 00:02:04.829 --> 00:02:07.170 an X and a Y chromosome, and having the genes 00:02:07.170 --> 00:02:09.870 on those set of chromosomes lead to the development 00:02:09.870 --> 00:02:13.210 of testes in typical males. And so I guess to 00:02:13.210 --> 00:02:16.810 simplify it, the way we define biological sex 00:02:16.810 --> 00:02:20.610 in biology is based on the phenotype or the gonads. 00:02:20.830 --> 00:02:22.969 So if you have testes or ovaries, so basically 00:02:22.969 --> 00:02:26.050 your reproductive organs, and that's how we kind 00:02:26.050 --> 00:02:28.229 of refer to it. at least in the field that I'm 00:02:28.229 --> 00:02:30.569 in and the way that we're approaching that biology. 00:02:30.750 --> 00:02:33.150 Gender, on the other hand, is a social construct. 00:02:33.409 --> 00:02:37.250 So it's the genders, what one identifies with 00:02:37.250 --> 00:02:40.849 or perceives themselves as. And that more broadly, 00:02:40.909 --> 00:02:44.349 the two categories is man or woman. So to kind 00:02:44.349 --> 00:02:46.789 of use the terminology correctly, which it's 00:02:46.789 --> 00:02:48.789 often not, and even in a lot of peer reviewed 00:02:48.789 --> 00:02:51.330 papers and a lot of really high impact papers, 00:02:51.490 --> 00:02:54.110 people will still interchange them. But if you're 00:02:54.110 --> 00:02:56.909 talking about what is actually. happening from 00:02:56.909 --> 00:02:58.969 a biology perspective sex is male and female 00:02:58.969 --> 00:03:02.389 and gender is man and woman and that means that 00:03:02.389 --> 00:03:05.349 comes up a lot in research is that mice don't 00:03:05.349 --> 00:03:07.330 have a gender they have a sex because we don't 00:03:07.330 --> 00:03:09.569 know mice can't tell us what they identify as 00:03:09.569 --> 00:03:11.250 right so they can be male or female they can't 00:03:11.250 --> 00:03:13.009 be you know that they don't have a gender and 00:03:13.009 --> 00:03:14.969 that's again to keep it simple i won't go into 00:03:14.969 --> 00:03:19.129 all the different variations of trend of um gender 00:03:19.129 --> 00:03:22.330 identity so i gave you just the two man and woman 00:03:22.330 --> 00:03:24.569 but yeah i won't go into the details of of all 00:03:24.569 --> 00:03:26.620 the in between because study biology. So we're 00:03:26.620 --> 00:03:29.180 interested in what's in between male and female. 00:03:29.280 --> 00:03:31.539 But we're here to talk to you about biology, 00:03:31.599 --> 00:03:33.360 not about the social constructs. So I'll stick 00:03:33.360 --> 00:03:37.500 to that. And then how that relates to DSD and 00:03:37.500 --> 00:03:41.199 transgender. So DSD stands for differences in 00:03:41.199 --> 00:03:44.180 sex development. It used to stand for disorders 00:03:44.180 --> 00:03:46.400 and sex development, but that was changed. It 00:03:46.400 --> 00:03:48.460 used to be termed as intersex, but that's also 00:03:48.460 --> 00:03:51.280 less commonly the medical term. So now we go 00:03:51.280 --> 00:03:53.900 with DSD, which is a difference in sex development. 00:03:54.060 --> 00:03:56.039 So a lot of what What my lab at the Hudson does 00:03:56.039 --> 00:04:00.539 is study those exact pathways of sex development. 00:04:00.659 --> 00:04:05.539 So how does an XX embryo lead to the eventual 00:04:05.539 --> 00:04:07.840 sexual characteristics? And what that means is 00:04:07.840 --> 00:04:11.740 about 1 % of the population, which is a lot more 00:04:11.740 --> 00:04:14.639 than what people tend to think, and that is kind 00:04:14.639 --> 00:04:17.800 of commonly thought, is born with a DSD. So that 00:04:17.800 --> 00:04:20.420 means they present with sexual characteristics 00:04:20.420 --> 00:04:24.300 that are not 100 % typical to male or 100 % typical 00:04:24.300 --> 00:04:26.279 to female, but are somewhere in between. And 00:04:26.279 --> 00:04:28.459 that's a really big range and a really big spectrum. 00:04:28.540 --> 00:04:31.920 So you can have anything from a partial sex reversal 00:04:31.920 --> 00:04:35.060 to a full sex reversal. So what we mean by partial 00:04:35.060 --> 00:04:38.660 is you are XX, you're presenting as a female, 00:04:38.819 --> 00:04:42.360 but you have some characteristics that are male 00:04:42.360 --> 00:04:44.720 -like. And that's why we use the word typical 00:04:44.720 --> 00:04:47.720 because 99 % of the population... that's how 00:04:47.720 --> 00:04:50.439 a male develops. 99 % of the population, that's 00:04:50.439 --> 00:04:52.420 how a female develops. So this is the typical 00:04:52.420 --> 00:04:56.089 pathway. If everything is coordinated. in a specific 00:04:56.089 --> 00:04:59.930 way. And variations to that pathway will lead 00:04:59.930 --> 00:05:03.069 to a difference in sex development. And that 00:05:03.069 --> 00:05:05.410 can be at several stages along the pathway, therefore 00:05:05.410 --> 00:05:09.149 leading to this spectrum. So that was partial 00:05:09.149 --> 00:05:11.329 sex reversal, meaning you still have the sex 00:05:11.329 --> 00:05:14.209 chromosomes that your phenotype or your gonads 00:05:14.209 --> 00:05:16.550 are presenting as, but maybe you have some variation. 00:05:16.629 --> 00:05:19.089 And then you have full sex reversal, where you 00:05:19.089 --> 00:05:21.629 can have an XX chromosome makeup, but you're 00:05:21.629 --> 00:05:24.759 actually presenting entirely as a male. male 00:05:24.759 --> 00:05:27.139 characteristics. So there's a range and everything 00:05:27.139 --> 00:05:30.680 in between. And so what my lab does is try to 00:05:30.680 --> 00:05:35.399 identify the genes that are or the variants in 00:05:35.399 --> 00:05:37.720 the genes that are causing those differences 00:05:37.720 --> 00:05:40.560 in sex development. So the main gene that was 00:05:40.560 --> 00:05:43.699 discovered several decades ago was SRY, the sex 00:05:43.699 --> 00:05:46.579 determining region on the Y chromosome is what 00:05:46.579 --> 00:05:49.339 SRY stands for. And it's a gene that lies on 00:05:49.339 --> 00:05:52.360 the Y chromosome. And generally, typically, if 00:05:52.360 --> 00:05:55.519 it's present, it leads to the development of 00:05:55.519 --> 00:05:59.189 testes. So... It's kind of like as a simplistic 00:05:59.189 --> 00:06:02.290 statement, if you have SRY, you'll develop testes. 00:06:02.329 --> 00:06:04.730 If you don't have SRY, you won't. But that's 00:06:04.730 --> 00:06:06.870 a very simple statement because the pathway is 00:06:06.870 --> 00:06:09.129 very complex. There's a lot of parts of the pathway 00:06:09.129 --> 00:06:12.110 that are already known. So which targets there 00:06:12.110 --> 00:06:15.170 are upstream or downstream of SRY. And there 00:06:15.170 --> 00:06:18.410 are also inhibitory pathways to then inhibit 00:06:18.410 --> 00:06:20.310 the development of ovaries at the same time. 00:06:20.350 --> 00:06:22.370 So it's a coordinated pathway. It's almost like 00:06:22.370 --> 00:06:23.870 you start with what's called the biopotential 00:06:23.870 --> 00:06:26.899 gonad. And it kind of has a, you know, an unknown 00:06:26.899 --> 00:06:29.639 fate at that point. And it depends on the presence 00:06:29.639 --> 00:06:32.139 of a multitude of different genes in the pathway. 00:06:32.339 --> 00:06:35.600 And if the right genes are present at the right 00:06:35.600 --> 00:06:37.459 time, so they're expressed at the right time, 00:06:37.500 --> 00:06:39.620 that bipotential gonad will differentiate into 00:06:39.620 --> 00:06:42.480 a testes. And if the right genes are present 00:06:42.480 --> 00:06:44.680 or not present at the right time, that bipotential 00:06:44.680 --> 00:06:46.519 gonad will differentiate into the ovaries. So 00:06:46.519 --> 00:06:48.579 it kind of has these two pathways that it can 00:06:48.579 --> 00:06:51.639 go down. That said... because it includes a number 00:06:51.639 --> 00:06:54.620 of genes that need to be coordinated and turned 00:06:54.620 --> 00:06:56.939 on at the right time in the right place, right, 00:06:57.040 --> 00:06:59.180 and you go and add. Then variations, whether 00:06:59.180 --> 00:07:00.800 it's at this point in the pathway or at this 00:07:00.800 --> 00:07:02.300 point, then all of a sudden you could find yourself 00:07:02.300 --> 00:07:04.439 coming towards the other pathway. So that can 00:07:04.439 --> 00:07:06.879 happen at multiple different stages, and that's 00:07:06.879 --> 00:07:09.899 where the complexity comes in. So there's about 00:07:09.899 --> 00:07:12.519 50 % of cases, and I'm giving a rough estimate 00:07:12.519 --> 00:07:14.860 because it depends on which type of DSD. If we're 00:07:14.860 --> 00:07:17.120 talking about an individual that's XY or an individual 00:07:17.120 --> 00:07:19.990 that's XX, but at least 50%. both categories 00:07:19.990 --> 00:07:22.629 have variations in genes that we haven't yet 00:07:22.629 --> 00:07:25.329 discovered or variants that we haven't yet discovered. 00:07:25.490 --> 00:07:28.389 So about 50 % of the cases that present will, 00:07:28.589 --> 00:07:30.990 you know, if a baby is born and presents with 00:07:30.990 --> 00:07:34.250 ambiguous genitalia or ambiguous sex characteristics, 00:07:34.269 --> 00:07:37.490 so kind of a mix or a mixture of both, then they 00:07:37.490 --> 00:07:41.810 usually undergo a DSD gene panel, which has 138, 00:07:41.850 --> 00:07:44.550 so approximately 140 genes that have been confirmed 00:07:44.550 --> 00:07:48.029 and identified to lead to DSDs. If they test 00:07:48.029 --> 00:07:50.529 positive, for any of those specific variations 00:07:50.529 --> 00:07:52.990 of those specific genes, then they have a diagnosis 00:07:52.990 --> 00:07:55.449 and they can be advised with their treatment 00:07:55.449 --> 00:07:58.769 options or kind of the way that that DSD tends 00:07:58.769 --> 00:08:01.170 to develop in people. And then the other kind 00:08:01.170 --> 00:08:04.569 of 50 plus percent don't fall on any of the genes 00:08:04.569 --> 00:08:06.730 on the gene panel. And that's the patients that 00:08:06.730 --> 00:08:09.540 we often get. So we'll get patients that. are 00:08:09.540 --> 00:08:12.319 called panel negative. So none of the genes that 00:08:12.319 --> 00:08:15.160 cause DSDs that we know of don't explain their 00:08:15.160 --> 00:08:18.920 DSD. And then we perform a mixture of whole exome 00:08:18.920 --> 00:08:21.079 sequencing or whole genome sequencing with a 00:08:21.079 --> 00:08:24.620 combination of other methods to identify the 00:08:24.620 --> 00:08:28.279 potentially causing variant or that DSD. Is it 00:08:28.279 --> 00:08:31.399 possible that it's not obvious at birth and the 00:08:31.399 --> 00:08:35.980 person gets to know later? And if yes, what circumstances 00:08:35.980 --> 00:08:39.440 would bring this topic about? Yeah. So because 00:08:39.440 --> 00:08:42.779 it's such a spectrum, there's a lot of answers 00:08:42.779 --> 00:08:44.559 to that question because depending on the type 00:08:44.559 --> 00:08:48.120 of DSD. But as an example, so the three kind 00:08:48.120 --> 00:08:51.220 of main types of DSDs that we categorize into 00:08:51.220 --> 00:08:54.539 are one is sex chromosome aneuploidies, which 00:08:54.539 --> 00:08:57.019 means you basically have a different number of 00:08:57.019 --> 00:08:59.419 sex chromosomes than what is typically found. 00:08:59.559 --> 00:09:02.820 So instead of having XY or XX, you have either 00:09:02.820 --> 00:09:05.899 XO, which is Turner syndrome. So females that 00:09:05.899 --> 00:09:08.269 have just one X chromosome and you have X. XXY, 00:09:08.429 --> 00:09:10.929 which is Klinefelter syndrome, so males that 00:09:10.929 --> 00:09:13.250 have two X chromosomes and a Y. And you have 00:09:13.250 --> 00:09:15.929 Jacobs syndrome, which is XYY, which is more 00:09:15.929 --> 00:09:19.110 rare. And that also leads to male development, 00:09:19.210 --> 00:09:21.929 but with two Y chromosomes. So a good example 00:09:21.929 --> 00:09:24.309 of individuals finding out later on is with these 00:09:24.309 --> 00:09:26.389 sex chromosome aneuploidies, because they have 00:09:26.389 --> 00:09:29.590 some mild phenotypes. And again, it ranges depending 00:09:29.590 --> 00:09:32.350 on the individual and what we call the mosaicism. 00:09:32.490 --> 00:09:35.769 So some cells can have just one X, some cells 00:09:35.769 --> 00:09:37.830 potentially have a combination. So depending 00:09:37.830 --> 00:09:40.830 on that individual's present genetic condition 00:09:40.830 --> 00:09:44.230 or kind of genetic makeup, they will present 00:09:44.230 --> 00:09:46.210 with different symptoms and potentially at different 00:09:46.210 --> 00:09:48.950 stages of life. So often what will happen either 00:09:48.950 --> 00:09:50.850 with Turner syndrome or Klinefelter syndrome 00:09:50.850 --> 00:09:54.090 is these people have problems with conceiving 00:09:54.090 --> 00:09:56.990 or problems with fertility. And upon fertility 00:09:56.990 --> 00:10:00.409 investigation, we'll find out that they have 00:10:00.409 --> 00:10:03.070 one X chromosome in a female or potentially two 00:10:03.070 --> 00:10:05.409 X chromosomes in Klinefelter men. So that's one 00:10:05.409 --> 00:10:07.649 example of how. that can be found later on. And 00:10:07.649 --> 00:10:09.649 then back to the other two types of DSDs that 00:10:09.649 --> 00:10:11.970 we talked about, sex chromosome aneuploidy types, 00:10:12.129 --> 00:10:16.889 then there's what we call 46XY and then 46XX. 00:10:17.029 --> 00:10:19.350 And what that means is that the individual has 00:10:19.350 --> 00:10:21.649 the two sets of sex chromosomes that are typical, 00:10:21.789 --> 00:10:25.149 right? Either XX or XY, but they have a partial 00:10:25.149 --> 00:10:29.409 or a full sex reversal. So a variation to their 00:10:29.409 --> 00:10:31.629 development, meaning someone that's XX isn't 00:10:31.629 --> 00:10:34.649 presenting phenotypically completely as an individual 00:10:34.649 --> 00:10:38.000 who is XX. X and vice versa with X, Y. Wow, super 00:10:38.000 --> 00:10:40.940 complicated to say the least. That's good. I 00:10:40.940 --> 00:10:43.980 really wanted to show it. Why do we care in sports 00:10:43.980 --> 00:10:47.440 whether the person developed typically or atypically? 00:10:47.600 --> 00:10:50.539 In the context of sports, and this is where, 00:10:50.679 --> 00:10:54.379 yeah, it just, it's complicated in biology. It's 00:10:54.379 --> 00:10:57.720 complicated in what we study. And so that obviously 00:10:57.720 --> 00:11:00.500 translates also to... to the sporting regulations 00:11:00.500 --> 00:11:03.679 and to the definitions in sport. So I'll go through 00:11:03.679 --> 00:11:06.220 kind of just a rough history of what's kind of 00:11:06.220 --> 00:11:08.679 happened. So update on the DSD participation. 00:11:08.940 --> 00:11:11.879 And I guess I'll keep my wording a bit vague 00:11:11.879 --> 00:11:14.100 because I'm not here to point fingers at anybody 00:11:14.100 --> 00:11:17.639 or at any body or organization. I'm a biologist 00:11:17.639 --> 00:11:20.460 or interested in the biology. And I'm here to 00:11:20.460 --> 00:11:22.259 discuss the facts of what we know and what we 00:11:22.259 --> 00:11:24.539 don't know and not to give my opinion on what 00:11:24.539 --> 00:11:26.600 I think the regulations should and shouldn't 00:11:26.600 --> 00:11:30.159 be. So the saga with DSD. participation is not 00:11:30.159 --> 00:11:32.220 new it's something that's come up in history 00:11:32.220 --> 00:11:36.039 but it really blew up around 2009 after the 800 00:11:36.039 --> 00:11:39.340 meters in the world championships and since then 00:11:39.340 --> 00:11:41.620 it went through a number of different regulations 00:11:41.620 --> 00:11:45.240 so first it was decided that females that wanted 00:11:45.240 --> 00:11:49.679 to compete in events from 400 meters to the mile 00:11:49.679 --> 00:11:52.539 in athletics had to have a testosterone concentration 00:11:52.539 --> 00:11:55.539 below 10 animals per liter that concentration 00:11:55.539 --> 00:11:57.360 i'll talk a little bit about the testosterone 00:11:57.360 --> 00:12:00.480 aspect That concentration recommendation or restriction 00:12:00.480 --> 00:12:03.399 then moved down to five nanomoles per liter, 00:12:03.500 --> 00:12:06.000 and then it moved down to two and a half in 2019. 00:12:06.240 --> 00:12:08.860 And that's where it sits right now. And there 00:12:08.860 --> 00:12:10.700 is a lot of debate around that. But what that 00:12:10.700 --> 00:12:14.440 meant is that females that had a DSD that caused 00:12:14.440 --> 00:12:17.080 them to have high testosterone levels were required, 00:12:17.220 --> 00:12:19.879 if they wanted to participate, to take medication 00:12:19.879 --> 00:12:23.360 to lower their testosterone levels below that 00:12:23.360 --> 00:12:26.340 allowed threshold. Could you just, my audience 00:12:26.340 --> 00:12:29.509 may not be... quite familiar with the normal, 00:12:30.129 --> 00:12:33.330 maybe typical ranges should be for females and 00:12:33.330 --> 00:12:37.289 for males. Why 10, 5, 2 .5? How it relates to 00:12:37.289 --> 00:12:41.429 male levels? So males have several folds higher 00:12:41.429 --> 00:12:44.309 levels of testosterone. A normal, you know, a 00:12:44.309 --> 00:12:47.070 typical male and a typical female. And there 00:12:47.070 --> 00:12:49.889 are conditions in females and that's what I was 00:12:49.889 --> 00:12:52.409 going to get to on the complexities in it because 00:12:52.409 --> 00:12:54.629 there are conditions in females such as PCOS, 00:12:54.629 --> 00:12:56.730 so polycystic ovary syndrome, which can lead 00:12:56.730 --> 00:12:59.610 to those higher levels, but it's a trait that 00:12:59.610 --> 00:13:02.490 we call sexually dimorphic, which means it totally 00:13:02.490 --> 00:13:04.870 doesn't overlap. So there are traits that have 00:13:04.870 --> 00:13:06.850 sex differences, for instance, height. If you 00:13:06.850 --> 00:13:08.149 look at a graph, you know, it's kind of like 00:13:08.149 --> 00:13:09.909 this, like, yes, on average, males are taller 00:13:09.909 --> 00:13:11.610 and females are shorter, but there's going to 00:13:11.610 --> 00:13:13.190 be an overlap. It's not like there's not males 00:13:13.190 --> 00:13:15.110 that have the same height as a female and vice 00:13:15.110 --> 00:13:17.009 versa. But when it comes to testosterone levels, 00:13:17.269 --> 00:13:20.049 it's like this, you know, like you can take someone's 00:13:20.049 --> 00:13:21.230 testosterone and you want to know if they're 00:13:21.519 --> 00:13:23.240 you know, if they're a male or a female, we're 00:13:23.240 --> 00:13:25.120 talking about to keep using the word typical 00:13:25.120 --> 00:13:27.620 to keep that in mind. So yeah, it's many, many 00:13:27.620 --> 00:13:30.879 folds higher in males. Okay. So if that's the 00:13:30.879 --> 00:13:35.240 case, why 10, 5, and 2 .5? Yeah. And that's what 00:13:35.240 --> 00:13:37.299 a lot of the debate and criticism has been around 00:13:37.299 --> 00:13:41.460 because those numbers, at least in science, whenever 00:13:41.460 --> 00:13:43.879 there are thresholds, we always see that as a 00:13:43.879 --> 00:13:45.879 little bit arbitrary. You know, we choose a p 00:13:45.879 --> 00:13:48.659 -value of 0 .05, but some people choose a p -value 00:13:48.659 --> 00:13:51.480 of, and a p -value is just how significant something 00:13:51.480 --> 00:13:55.440 is in science, right? Of 0 .05 or 0 .05 or 0 00:13:55.440 --> 00:13:58.840 .01 or 0 .01. So, you know, choosing a threshold 00:13:58.840 --> 00:14:00.419 that's going to decide, you know, if you're above 00:14:00.419 --> 00:14:03.159 or below that always is going to have a sense 00:14:03.159 --> 00:14:06.220 of subjectivity to it and I guess arbitrariness 00:14:06.220 --> 00:14:09.639 to it. And I think that's why the numbers were 00:14:09.639 --> 00:14:12.440 adjusted every few years is because there really 00:14:12.440 --> 00:14:15.720 wasn't evidence to support that threshold. So 00:14:15.720 --> 00:14:19.700 there were studies done trying to measure performance. 00:14:20.009 --> 00:14:22.289 females and their levels of testosterone and 00:14:22.289 --> 00:14:25.230 correlate levels of testosterone to performance 00:14:25.230 --> 00:14:28.330 but we know that performance is so multifaceted 00:14:28.330 --> 00:14:31.090 so how can you you know single that one thing 00:14:31.090 --> 00:14:32.950 and say oh this person has high testosterone 00:14:32.950 --> 00:14:34.929 therefore they have better performance when there 00:14:34.929 --> 00:14:36.909 was maybe another person that had that same level 00:14:36.909 --> 00:14:38.850 and they had lower performance so it's it's not 00:14:38.850 --> 00:14:40.929 a black and white the levels that were decided 00:14:40.929 --> 00:14:43.210 were debated on and that's why they kept coming 00:14:43.210 --> 00:14:46.230 down and the data that was out there to support 00:14:46.230 --> 00:14:48.730 that threshold was very weak yeah and in addition 00:14:48.730 --> 00:14:50.389 to that There's different reasons for having 00:14:50.389 --> 00:14:52.830 high testosterone and there's different ranges. 00:14:53.110 --> 00:14:55.990 So if you have PCOS and it's also all about the 00:14:55.990 --> 00:14:58.730 receptors as well, you can have high testosterone, 00:14:58.909 --> 00:15:01.009 but is it bioavailable? Is your body actually 00:15:01.009 --> 00:15:03.970 able to have the sensitivity in the receptors 00:15:03.970 --> 00:15:07.009 to respond to those higher levels? So it's a 00:15:07.009 --> 00:15:08.669 combination of a lot of different things that 00:15:08.669 --> 00:15:11.450 are going to present differently. an individual, 00:15:11.649 --> 00:15:13.629 depending on the reason that they have that high 00:15:13.629 --> 00:15:15.210 testosterone and the background of everything 00:15:15.210 --> 00:15:17.549 else that they have. So it's, there's kind of 00:15:17.549 --> 00:15:20.250 not been any single study that's been able to, 00:15:20.289 --> 00:15:23.970 you know, really answer that question fully because 00:15:23.970 --> 00:15:26.950 most studies and most of what we know about testosterone 00:15:26.950 --> 00:15:30.610 historically was done in studies in males. And 00:15:30.610 --> 00:15:33.129 now there are more studies coming out in females 00:15:33.129 --> 00:15:36.110 and we'll get to transgender, gender -firming 00:15:36.110 --> 00:15:38.350 hormone therapy, looking at the effect of when 00:15:38.350 --> 00:15:41.039 you take exogenous, so out. of your body testosterone 00:15:41.039 --> 00:15:43.919 and what that does. But when it comes to having 00:15:43.919 --> 00:15:46.620 high endogenous testosterone levels that have 00:15:46.620 --> 00:15:48.899 high variability and a multitude of different 00:15:48.899 --> 00:15:51.679 functions, it's really hard to answer that question 00:15:51.679 --> 00:15:54.580 of exactly at what threshold do you get a performance 00:15:54.580 --> 00:15:57.419 benefit with testosterone in females. It's just 00:15:57.419 --> 00:15:59.940 not really well known and the data is not there 00:15:59.940 --> 00:16:03.299 to support that. Okay, so if we think DSDs, we 00:16:03.299 --> 00:16:06.379 understand now that it's a spectrum and the things 00:16:06.379 --> 00:16:09.879 may diverge from the typical pathway. on many, 00:16:09.960 --> 00:16:14.679 many levels. So now in terms of sport, the different 00:16:14.679 --> 00:16:18.000 DSDs will have different presentations in terms 00:16:18.000 --> 00:16:21.000 of potential performance improvement. Exactly. 00:16:21.019 --> 00:16:24.700 And because it's 1 % of the population and in 00:16:24.700 --> 00:16:28.000 that 1 % that splits to a certain percent being 00:16:28.000 --> 00:16:30.320 males and a certain percent presenting as females, 00:16:30.419 --> 00:16:32.500 that's going to be even less. And then you have 00:16:32.500 --> 00:16:33.899 the number of those people that actually ended 00:16:33.899 --> 00:16:37.740 up in sports or having skills in a specific sport. 00:16:37.879 --> 00:16:40.340 So that's... reduces it even more. And then you 00:16:40.340 --> 00:16:43.389 have the ones that... you know, they have variable 00:16:43.389 --> 00:16:45.509 presentations of what are the genetic causes 00:16:45.509 --> 00:16:48.090 and then it splits it up even more. So you have 00:16:48.090 --> 00:16:50.769 a really small number of people to represent, 00:16:50.870 --> 00:16:52.909 you know, each one of those different categories 00:16:52.909 --> 00:16:54.909 or however many there even are. But the point 00:16:54.909 --> 00:16:57.190 is to say that when it comes, so I didn't mention, 00:16:57.230 --> 00:17:00.149 so the latest ruling is what I was going to add. 00:17:00.250 --> 00:17:03.529 The latest ruling that was just now before the 00:17:03.529 --> 00:17:07.109 Tokyo World Championship, so just in September, 00:17:07.289 --> 00:17:11.579 was that the testosterone for... in the female 00:17:11.579 --> 00:17:14.720 category needed to be below 2 .5 animals per 00:17:14.720 --> 00:17:17.200 liter. So that stayed. And individuals who wish 00:17:17.200 --> 00:17:20.660 to compete as a female needed to undergo a test 00:17:20.660 --> 00:17:23.920 to see if they have the SRY gene or not. So we 00:17:23.920 --> 00:17:26.539 talked before that the SRY gene is one of the 00:17:26.539 --> 00:17:29.259 key members in the pathway to determine if you 00:17:29.259 --> 00:17:31.640 develop testes or if you develop ovaries. But, 00:17:31.660 --> 00:17:33.859 and this is where the big buck comes in and where 00:17:33.859 --> 00:17:38.299 the DSD researchers are kind of trying to, I 00:17:38.299 --> 00:17:41.609 guess, make it clear that it's a lot more complex 00:17:41.609 --> 00:17:45.190 than that. And it's not just one gene that decides 00:17:45.190 --> 00:17:48.470 if you have testes development or ovaries development. 00:17:48.750 --> 00:17:52.369 So there are what we call SRY negative cases 00:17:52.369 --> 00:17:55.170 and SRY positive cases. And that means that, 00:17:55.230 --> 00:17:59.430 for example, an individual that is XY could not 00:17:59.430 --> 00:18:02.890 have the sry gene and could have crazy things 00:18:02.890 --> 00:18:04.910 happen in genetics genes can get moved on to 00:18:04.910 --> 00:18:07.849 different chromosomes and chromosomes can rearrange 00:18:07.849 --> 00:18:11.029 and split up in meiosis and separate strangely 00:18:11.029 --> 00:18:13.529 like a lot of strange things happen and simply 00:18:13.529 --> 00:18:16.829 having sry or not having sry doesn't doesn't 00:18:16.829 --> 00:18:20.190 determine the sex development 100 it explains 00:18:20.190 --> 00:18:22.569 a lot of the cases but not all of the cases so 00:18:22.569 --> 00:18:25.130 that means that you can have a female so an xx 00:18:25.130 --> 00:18:27.930 chromosome complement but there can be a mutation 00:18:27.930 --> 00:18:30.960 in another gene such as SOX9, and that can lead 00:18:30.960 --> 00:18:34.640 to some male sex determination pathways. So that's 00:18:34.640 --> 00:18:38.339 just an example of why this SRY simple gene test 00:18:38.339 --> 00:18:41.460 to decide if a female can compete or not doesn't 00:18:41.460 --> 00:18:43.960 actually cover the range or the spectrum of conditions 00:18:43.960 --> 00:18:46.019 because there can be mutations. Well, there can 00:18:46.019 --> 00:18:47.900 be. There are mutations in other genes, ones 00:18:47.900 --> 00:18:49.920 that are known. but also ones that are not known. 00:18:50.039 --> 00:18:53.059 That will lead to male sex determination in a 00:18:53.059 --> 00:18:56.440 female and vice versa. So a simple test is just, 00:18:56.519 --> 00:18:59.099 well, the biology is complicated. And, you know, 00:18:59.099 --> 00:19:01.200 where do you draw the line for female enough? 00:19:01.279 --> 00:19:04.240 We don't even know that in biology. So I don't 00:19:04.240 --> 00:19:06.019 know how you would draw that line for sport. 00:19:06.140 --> 00:19:09.319 It's just too complicated. So I guess the other 00:19:09.319 --> 00:19:12.319 detail to add to the ruling that was made back 00:19:12.319 --> 00:19:17.019 in September is that females with, so women that 00:19:17.019 --> 00:19:20.380 were XY, but are presenting as females that have 00:19:20.380 --> 00:19:22.380 what's called androgen insensitivity syndrome 00:19:22.380 --> 00:19:24.400 are allowed to compete in the female category 00:19:24.400 --> 00:19:27.380 as long as their testosterone is at a low level. 00:19:27.480 --> 00:19:30.839 And this is because they don't have the receptors 00:19:30.839 --> 00:19:33.140 to actually respond to that. So that was things 00:19:33.140 --> 00:19:36.000 that are based off data and rulings that are 00:19:36.000 --> 00:19:38.200 based off of science. So it's nice to see when 00:19:38.200 --> 00:19:40.920 the policies and guidelines do have some science 00:19:40.920 --> 00:19:43.809 rationale. to them because that was argued. Well, 00:19:43.910 --> 00:19:45.369 they have higher testosterone, but they can't 00:19:45.369 --> 00:19:47.490 actually use it. So it's not actually helping 00:19:47.490 --> 00:19:50.670 them. But the thing that still stands, that is 00:19:50.670 --> 00:19:54.059 not. completely aligning with the science of 00:19:54.059 --> 00:19:59.119 DSDs is the fact that now the SRY gene is deemed 00:19:59.119 --> 00:20:01.720 the, you know, be -all, know -all to if you have 00:20:01.720 --> 00:20:04.660 a male or female sex development. And we simply 00:20:04.660 --> 00:20:06.599 know that that's not that simple. And there's 00:20:06.599 --> 00:20:08.980 other genes involved. Okay. Should we move to 00:20:08.980 --> 00:20:12.579 transgender athletes? Yes. So I have much less 00:20:12.579 --> 00:20:16.359 to say about this because we do study a little 00:20:16.359 --> 00:20:19.660 bit in my current lab and my past lab, but it's 00:20:19.660 --> 00:20:22.589 not currently... that, how do I say it? No, but 00:20:22.589 --> 00:20:26.710 I think we need just to complement the topic 00:20:26.710 --> 00:20:30.329 of the athletes and to make it maybe not full 00:20:30.329 --> 00:20:33.130 picture, but maybe a little bit more rich picture. 00:20:33.190 --> 00:20:36.490 So we have these athletes who wear the jeans 00:20:36.490 --> 00:20:40.690 and the development are varying from the typical. 00:20:40.769 --> 00:20:43.950 And now we have transgender athletes who at some 00:20:43.950 --> 00:20:47.650 point decided that they present or want to present 00:20:47.650 --> 00:20:51.289 as the other gender. So that has consequences. 00:20:51.660 --> 00:20:55.339 in terms of fairness and participation in sports. 00:20:55.460 --> 00:20:58.640 So from that perspective, who are transgender 00:20:58.640 --> 00:21:01.660 athletes and how they differ from DSD athletes? 00:21:02.000 --> 00:21:06.240 Yes, well said. So I think what's important to 00:21:06.240 --> 00:21:10.380 understand with transgender athletes and the 00:21:10.380 --> 00:21:14.200 decisions that they make around their process 00:21:14.200 --> 00:21:17.839 for if they want to perform gender from hormone 00:21:17.839 --> 00:21:21.819 therapy or not is understanding what... administering 00:21:21.819 --> 00:21:23.940 hormones does to the body and to performance. 00:21:24.259 --> 00:21:27.900 So two kind of main things in that to understand 00:21:27.900 --> 00:21:31.299 is what we call organizational and activational 00:21:31.299 --> 00:21:33.920 hormone effects. And what that means is organizational 00:21:33.920 --> 00:21:38.160 is the lifelong exposure to a specific hormone 00:21:38.160 --> 00:21:40.640 level, so having high testosterone in males or 00:21:40.640 --> 00:21:43.579 higher estrogen in females, means that there 00:21:43.579 --> 00:21:46.380 are things that will happen in the body and the 00:21:46.380 --> 00:21:48.559 structure in your physiology that are irreversible. 00:21:48.680 --> 00:21:51.059 So a good example, a well -known studied example, 00:21:51.240 --> 00:21:54.119 is that there's a very specific time window in 00:21:54.119 --> 00:21:56.740 embryonic development that having high testosterone 00:21:56.740 --> 00:22:00.569 at that time leads to development of a specific 00:22:00.569 --> 00:22:02.990 region of the brain to be bigger and that region 00:22:02.990 --> 00:22:05.430 of the brain is again in typical males and females 00:22:05.430 --> 00:22:08.829 is always larger in males and smaller in females 00:22:08.829 --> 00:22:12.259 because there's that critical window of testosterone 00:22:12.259 --> 00:22:15.640 exposure. And if you treat developing female 00:22:15.640 --> 00:22:18.019 embryos with testosterone during that critical 00:22:18.019 --> 00:22:21.279 period, they will develop the male type size 00:22:21.279 --> 00:22:24.400 for that brain region. But if you give the testosterone 00:22:24.400 --> 00:22:26.839 later on outside of that critical period, then 00:22:26.839 --> 00:22:28.700 they won't. That brain region will develop as 00:22:28.700 --> 00:22:31.440 it does in females. So it's to show that there 00:22:31.440 --> 00:22:34.000 are critical periods in development that rely 00:22:34.000 --> 00:22:36.920 on specific hormone levels and either having 00:22:36.920 --> 00:22:39.079 or not having them at the right time is going 00:22:39.079 --> 00:22:41.859 to... to confer sex differences that remain for 00:22:41.859 --> 00:22:45.059 life and aren't reversible. So growing up with 00:22:45.059 --> 00:22:48.059 a certain hormone level and having that exposure 00:22:48.059 --> 00:22:50.859 throughout your in utero and throughout your 00:22:50.859 --> 00:22:53.599 life is going to set up some differences that 00:22:53.599 --> 00:22:55.400 are not going to be reversed. That's what we 00:22:55.400 --> 00:22:57.480 call organizational. The activational hormone 00:22:57.480 --> 00:22:59.839 differences means that those are kind of the 00:22:59.839 --> 00:23:02.880 acute effects of hormones and those can be reversed. 00:23:03.200 --> 00:23:05.799 So you can have taking testosterone can have 00:23:05.799 --> 00:23:08.440 some immediate effects on your self -signal. 00:23:08.460 --> 00:23:11.579 on your cell pathways that respond to that. And 00:23:11.579 --> 00:23:13.740 if you then remove that, then that pathway then 00:23:13.740 --> 00:23:16.019 stops that signaling or, you know, goes back 00:23:16.019 --> 00:23:18.339 to what it was before. So there are effects that 00:23:18.339 --> 00:23:21.460 are long term and irreversible and that happen 00:23:21.460 --> 00:23:23.319 from long term exposure and effects that are 00:23:23.319 --> 00:23:25.220 that are reversible. So I think understanding 00:23:25.220 --> 00:23:28.480 that and the field is still in its infancy and 00:23:28.480 --> 00:23:31.740 understanding exactly what the long term effects 00:23:31.740 --> 00:23:35.160 are of gender affirming hormone therapy in transgender 00:23:35.160 --> 00:23:37.740 individuals. So I think it's something think 00:23:37.740 --> 00:23:39.759 that's quite a hot topic right now. And I think 00:23:39.759 --> 00:23:41.779 that we're going to see a lot more studies coming 00:23:41.779 --> 00:23:43.779 out on it in the coming years. So that's something 00:23:43.779 --> 00:23:46.279 to keep your eyes open for. But a lot is looking 00:23:46.279 --> 00:23:50.339 at, you know, what risks or what immune differences 00:23:50.339 --> 00:23:53.799 or what are the effects on the physiology and 00:23:53.799 --> 00:23:55.819 non -performance that are going to come about. 00:23:55.980 --> 00:23:59.220 So it's trickling in and we are seeing a little 00:23:59.220 --> 00:24:01.019 bit of, you know, the effects of strength performance 00:24:01.019 --> 00:24:03.319 if you take testosterone, if you take estrogen, 00:24:03.440 --> 00:24:05.480 and you do see an increase in strength in specific 00:24:05.480 --> 00:24:07.789 tests with testosterone. and a decrease with 00:24:07.789 --> 00:24:09.910 reducing testosterone and increasing estrogen. 00:24:10.029 --> 00:24:11.890 But I think that there's just a lot still left 00:24:11.890 --> 00:24:14.930 to understand there. And yeah, there's also important 00:24:14.930 --> 00:24:17.390 to take into consideration how it affects the 00:24:17.390 --> 00:24:19.490 rest of your health. So there is an increase 00:24:19.490 --> 00:24:23.609 in risk with having thrombotic events as well 00:24:23.609 --> 00:24:27.710 as a few other cardiovascular events and having 00:24:27.710 --> 00:24:30.730 specific genetic predispositions to those events 00:24:30.730 --> 00:24:33.289 might exacerbate that. So it's very much still 00:24:33.289 --> 00:24:35.789 in the process and young and understanding the 00:24:35.789 --> 00:24:39.769 exact. effects of taking exogenous hormones for 00:24:39.769 --> 00:24:42.130 a long period and what that does so i think when 00:24:42.130 --> 00:24:45.250 it comes to transgender athletes and the decisions 00:24:45.250 --> 00:24:48.089 that that they can make for themselves is that 00:24:48.089 --> 00:24:51.049 just having the knowledge of what we already 00:24:51.049 --> 00:24:54.569 know and what the effects can be for that person 00:24:54.569 --> 00:24:57.730 will allow them to make the decision of you know 00:24:57.730 --> 00:24:59.730 what they want to do because there are the regulations 00:24:59.730 --> 00:25:03.009 set out which is having the testosterone levels 00:25:03.009 --> 00:25:05.680 at a certain level and if they want to in the 00:25:05.680 --> 00:25:08.519 female category, then that is something to consider 00:25:08.519 --> 00:25:10.059 because that's something that they have control 00:25:10.059 --> 00:25:12.779 over as opposed to the DSD athletes, which is 00:25:12.779 --> 00:25:14.880 different because that's made endogenously. It's 00:25:14.880 --> 00:25:17.839 made from within. it would be taking something 00:25:17.839 --> 00:25:20.779 external to reduce those levels, while in transgender 00:25:20.779 --> 00:25:24.839 athletes, they can choose to change those levels 00:25:24.839 --> 00:25:27.500 to be higher as opposed to lower. So yeah, I 00:25:27.500 --> 00:25:30.160 think when it comes to transgender athlete participation, 00:25:30.460 --> 00:25:35.539 it's less complex and there's more power in the 00:25:35.539 --> 00:25:38.480 individual's decisions that they can make in 00:25:38.480 --> 00:25:41.220 order to confer or kind of confer to the guidelines 00:25:41.220 --> 00:25:43.039 and then be able to compete in the category, 00:25:43.299 --> 00:25:45.480 in the female category. Okay, so what I'm hearing 00:25:45.480 --> 00:25:49.059 is... From the embryo, there are differences 00:25:49.059 --> 00:25:52.880 between female embryos and male embryos and how 00:25:52.880 --> 00:25:56.200 they develop. And these differences grow with 00:25:56.200 --> 00:25:59.480 the long -term exposure to the typical hormonal 00:25:59.480 --> 00:26:02.420 profile the female or male will have. So transgender 00:26:02.420 --> 00:26:05.599 athletes are different fundamentally. And there 00:26:05.599 --> 00:26:09.240 are differences that cannot be changed or controlled 00:26:09.240 --> 00:26:13.720 for using the gender -affirming hormonal therapy. 00:26:13.940 --> 00:26:17.019 So that's... obvious on the basis of the science. 00:26:17.160 --> 00:26:20.440 Now, how much it influences performance, that's 00:26:20.440 --> 00:26:24.700 where the gray area is and where the investigations 00:26:24.700 --> 00:26:28.680 are. Am I understanding correctly? Yes, I would 00:26:28.680 --> 00:26:32.920 say so. I would say gray, it's not as gray as 00:26:32.920 --> 00:26:36.019 DSDs, let's put it that way. So we know what 00:26:36.019 --> 00:26:39.099 taking exogenous hormones can do to your performance 00:26:39.099 --> 00:26:42.099 immediately, but I think we don't fully know. 00:26:42.160 --> 00:26:44.680 So exactly what those hormones influence. Lewin's. 00:26:44.779 --> 00:26:47.519 But I think... It's, you know, even intuitively 00:26:47.519 --> 00:26:50.299 and understanding and looking at a male and a 00:26:50.299 --> 00:26:53.039 female athlete and the size difference and all 00:26:53.039 --> 00:26:54.740 the other sex differences that we talked about 00:26:54.740 --> 00:26:56.839 in the previous recording is there are going 00:26:56.839 --> 00:26:59.359 to be established sex differences that are not 00:26:59.359 --> 00:27:02.180 going to be able to be reversed. So, yes, taking 00:27:02.180 --> 00:27:04.900 exogenous hormones or gender affirming hormone 00:27:04.900 --> 00:27:08.460 therapy will will shift those numbers a bit strength 00:27:08.460 --> 00:27:11.240 wise, performance wise. But the difference between 00:27:11.240 --> 00:27:13.980 male and female performance is so large that, 00:27:14.019 --> 00:27:16.279 you know, that's kind of how. I see it. So there's 00:27:16.279 --> 00:27:18.319 more left to understand. I'll put it, I'll agree 00:27:18.319 --> 00:27:21.220 with that, but we know enough to know that, that 00:27:21.220 --> 00:27:24.359 the lifelong exposure to, to hormones and even, 00:27:24.380 --> 00:27:26.819 even not lifelong, even if people undergo, you 00:27:26.819 --> 00:27:28.759 know, hormone replacement therapy earlier on, 00:27:29.000 --> 00:27:31.799 there's still E and utero differences and, and 00:27:31.799 --> 00:27:34.240 going through puberty that are going to be, yeah, 00:27:34.259 --> 00:27:36.500 irreversible in a sense. Do we know anything 00:27:36.500 --> 00:27:41.200 about the, for the transgender individuals, maybe 00:27:41.200 --> 00:27:43.019 not necessarily artists, because I don't think 00:27:43.019 --> 00:27:45.690 we have enough research. to draw on that. But 00:27:45.690 --> 00:27:48.930 how the gender affirming hormonal therapy influences 00:27:48.930 --> 00:27:53.990 risks of developing health conditions or diseases 00:27:53.990 --> 00:27:57.809 that are typically correlated or are more common 00:27:57.809 --> 00:28:02.490 in one or the other sex in typical lifelong exposure? 00:28:02.829 --> 00:28:05.430 I love that question. It's a great question. 00:28:05.549 --> 00:28:08.490 I think it's fascinating. When we are able to 00:28:08.490 --> 00:28:10.809 hopefully one day answer that, that is very much 00:28:10.809 --> 00:28:13.670 kind of connects to a lot of the research. that 00:28:13.670 --> 00:28:15.950 we're doing, which is understanding the basis 00:28:15.950 --> 00:28:19.549 or the reason for sex differences in conditions. 00:28:19.789 --> 00:28:21.670 And we talked about last time, I think, that 00:28:21.670 --> 00:28:23.890 there are diseases that are more prevalent in 00:28:23.890 --> 00:28:26.750 males where the symptoms are more severe in males 00:28:26.750 --> 00:28:29.890 and vice versa in females. And a lot is still 00:28:29.890 --> 00:28:31.930 understanding what are the drivers of that, if 00:28:31.930 --> 00:28:35.369 it is more sex chromosome genes or if it is more 00:28:35.369 --> 00:28:37.890 hormones. And the more that we've been able to 00:28:37.890 --> 00:28:39.730 do, we've been able to answer some of those questions 00:28:39.730 --> 00:28:41.690 around some of those diseases. And I think that 00:28:41.690 --> 00:28:44.619 that will tie in. really interestingly with your 00:28:44.619 --> 00:28:47.500 exact question, which is which diseases are we 00:28:47.500 --> 00:28:51.140 potentially protecting or becoming or exacerbating 00:28:51.140 --> 00:28:53.960 the risk to in males or females who are undergoing 00:28:53.960 --> 00:28:56.920 hormone replacement therapy? From what I know, 00:28:56.980 --> 00:28:59.500 there's not enough out there to answer that question, 00:28:59.640 --> 00:29:01.339 but I think that's going to come out as a really 00:29:01.339 --> 00:29:03.839 interesting question to answer. But for transgender 00:29:03.839 --> 00:29:06.839 individuals, but also for the rest of the population 00:29:06.839 --> 00:29:10.700 as well. I think as it does relate to the nice 00:29:10.700 --> 00:29:12.799 intersection between you know, that we're talking 00:29:12.799 --> 00:29:15.220 about performance and sports, but also about 00:29:15.220 --> 00:29:17.339 health. Because, of course, at the end of the 00:29:17.339 --> 00:29:19.019 day, we want to be healthy so that we can compete 00:29:19.019 --> 00:29:21.720 in our sport, right? So knowing the broader implications 00:29:21.720 --> 00:29:24.880 of hormones at the different stages and what 00:29:24.880 --> 00:29:26.759 it means to be taking them at different stages 00:29:26.759 --> 00:29:29.819 for your health is, yeah, a growing body of evidence, 00:29:30.000 --> 00:29:32.240 I would say. So there's a bit known as what I 00:29:32.240 --> 00:29:33.980 just mentioned, but there's still a lot left 00:29:33.980 --> 00:29:35.920 to understand with that. I don't think there's 00:29:35.920 --> 00:29:38.640 going to be one fair solution that is inclusive 00:29:38.640 --> 00:29:42.420 of all and fair to all. Yeah, there's just so 00:29:42.420 --> 00:29:45.660 much complexity in it. So I think the more we 00:29:45.660 --> 00:29:49.380 can study this, these conditions and how they 00:29:49.380 --> 00:29:51.059 relate to performance, the more we can design 00:29:51.059 --> 00:29:53.500 experiments that really help us to understand 00:29:53.500 --> 00:29:56.660 what testosterone is doing in females and in 00:29:56.660 --> 00:29:58.859 female muscle and in female performance. The 00:29:58.859 --> 00:30:01.160 best that we can design those experiments and 00:30:01.160 --> 00:30:05.299 answer that question and have a threshold that 00:30:05.299 --> 00:30:07.680 maybe is really based off of strong scientific 00:30:07.680 --> 00:30:10.140 evidence. You know, you would say you would have 00:30:10.140 --> 00:30:12.250 a gene. panel and you could look at all the DSD 00:30:12.250 --> 00:30:14.529 genes and then you can make decisions. But yeah, 00:30:14.569 --> 00:30:16.990 there will be individuals that fall in that in 00:30:16.990 --> 00:30:20.210 -between spectrum. And that's a lot of the issues 00:30:20.210 --> 00:30:23.309 that we also, that also individuals with DSDs 00:30:23.309 --> 00:30:26.430 will experience with making medical decisions 00:30:26.430 --> 00:30:29.029 with their conditions is, you know, if you're 00:30:29.029 --> 00:30:31.309 somewhere in the middle, how do you choose which, 00:30:31.430 --> 00:30:33.750 you know, it's hard to draw a line in biology 00:30:33.750 --> 00:30:36.410 in that sense. So I think it's hard to draw a 00:30:36.410 --> 00:30:39.170 line in sport as well, which I think I kind of 00:30:39.170 --> 00:30:41.470 repeated. this before, but I think, yeah, my 00:30:41.470 --> 00:30:45.049 simple answer is that it's too complex. And there's, 00:30:45.049 --> 00:30:47.549 in my opinion, there's just not going to be one 00:30:47.549 --> 00:30:50.390 solution that fits for all. And the more that 00:30:50.390 --> 00:30:52.390 we can base it on scientific evidence and strong 00:30:52.390 --> 00:30:55.390 scientific evidence that's robust and not biased, 00:30:55.589 --> 00:30:58.089 just the most, it'll be the most fair that we 00:30:58.089 --> 00:31:00.329 can have for the most people. But yeah, I think 00:31:00.329 --> 00:31:02.390 that's the best that we can do. All right. Is 00:31:02.390 --> 00:31:04.650 there anything I didn't ask about, but you think 00:31:04.650 --> 00:31:08.170 it's important to bring while we're on this topic 00:31:08.170 --> 00:31:10.779 today? Yeah. As long as you think that I explained 00:31:10.779 --> 00:31:12.940 the sex development pathways and how it doesn't 00:31:12.940 --> 00:31:15.400 solely rely on SRY, because that was the main 00:31:15.400 --> 00:31:18.460 takeaway that I wanted to get across here, because 00:31:18.460 --> 00:31:21.200 I know from friends who competed in the last 00:31:21.200 --> 00:31:23.900 world championships that, you know, they did 00:31:23.900 --> 00:31:26.579 their SRY test and all was good and well, but 00:31:26.579 --> 00:31:29.099 the athletes don't actually understand the meaning 00:31:29.099 --> 00:31:31.720 of it, I think, at a deeper level. And not that 00:31:31.720 --> 00:31:33.680 I expect people to, because it is complex and, 00:31:33.740 --> 00:31:35.960 you know, the average person isn't studying sex 00:31:35.960 --> 00:31:38.059 development pathways in their free time. But 00:31:38.059 --> 00:31:39.859 I think that when you're subjected to take a 00:31:39.859 --> 00:31:41.359 test, that's going to tell you something about 00:31:41.359 --> 00:31:43.680 yourself. And when all of your peers that are 00:31:43.680 --> 00:31:45.720 competing are subjected to take that test, I 00:31:45.720 --> 00:31:48.599 think that there should be more information out 00:31:48.599 --> 00:31:51.420 there to understanding the complexity of it and 00:31:51.420 --> 00:31:54.619 what it really means to have an SRY test. Because 00:31:54.619 --> 00:31:57.099 I don't know if I touched upon this, but simply 00:31:57.099 --> 00:32:01.019 having the regulations state that SRY is used 00:32:01.019 --> 00:32:03.500 as a proxy to determine if you have a Y chromosome 00:32:03.500 --> 00:32:05.420 or not. And that's their kind of their bottom 00:32:05.420 --> 00:32:07.140 line. If you have SRY, then you're going to have 00:32:07.140 --> 00:32:08.400 a Y chromosome. Y chromosome and vice versa. 00:32:08.519 --> 00:32:11.220 But that's the part that's just not 100 % true 00:32:11.220 --> 00:32:13.799 because you can have or not have S or Y, and 00:32:13.799 --> 00:32:15.900 that's irregardless of having a Y chromosome 00:32:15.900 --> 00:32:18.819 or not. So I think, yeah, as long as my main 00:32:18.819 --> 00:32:21.279 point came across, which is that, you know, the 00:32:21.279 --> 00:32:23.480 test that's currently the regulation is trying 00:32:23.480 --> 00:32:25.680 to make something gray, black, or white is what 00:32:25.680 --> 00:32:27.319 I'd say at the end of the day. And I think that 00:32:27.319 --> 00:32:29.900 the general population or the population that's 00:32:29.900 --> 00:32:32.859 interested in sports will gain from understanding 00:32:32.859 --> 00:32:36.950 what that really means. And also in their attitude 00:32:36.950 --> 00:32:40.250 towards dsd and their attitude towards towards 00:32:40.250 --> 00:32:43.109 sports and fairness because yeah it's just at 00:32:43.109 --> 00:32:44.890 the end of the day those are people with conditions 00:32:44.890 --> 00:32:48.109 that they didn't choose to have and not that 00:32:48.109 --> 00:32:50.809 and it's not necessarily a bad thing so yeah 00:32:50.809 --> 00:32:53.349 and i think and my other main thing that i want 00:32:53.349 --> 00:32:56.750 to make sure got across is that dsd and transgender 00:32:56.750 --> 00:33:00.150 those are two entirely different situations and 00:33:00.150 --> 00:33:01.890 i think that commonly they're grouped together 00:33:01.890 --> 00:33:05.569 and that's not fair to either of them right with 00:33:05.710 --> 00:33:08.329 with differing reasons for their circumstances. 00:33:08.849 --> 00:33:11.130 And yeah, I just think that the more knowledge 00:33:11.130 --> 00:33:13.690 that anyone has, the more they can make an informed 00:33:13.690 --> 00:33:16.150 decision that is the best for them and suits 00:33:16.150 --> 00:33:19.390 them the best. So people that are involved in 00:33:19.390 --> 00:33:21.609 athletics or involved in sports are very interested 00:33:21.609 --> 00:33:23.670 in a lot of coaches and stuff that they just 00:33:23.670 --> 00:33:25.589 want to understand. Like the recent regulations, 00:33:25.869 --> 00:33:28.609 what do they mean? Is it fair? Is it not fair? 00:33:28.849 --> 00:33:31.089 How much of it is evidence -driven? How much 00:33:31.089 --> 00:33:34.230 of it is political? So I think that I've come 00:33:34.230 --> 00:33:35.869 across a number of people that are just really 00:33:35.869 --> 00:33:37.750 interested in understanding what the regulations 00:33:37.750 --> 00:33:40.490 even mean. Where did it come from? So, yeah. 00:33:40.630 --> 00:33:43.930 Right. And if it affects the athletes, it's good 00:33:43.930 --> 00:33:48.089 to understand how. Because when you see cases 00:33:48.089 --> 00:33:51.630 in media, you make up your mind on the small 00:33:51.630 --> 00:33:54.670 part that you understand. And then you say, oh, 00:33:54.730 --> 00:33:57.329 they should do this. black and white solution 00:33:57.329 --> 00:34:00.089 but what you're showing here is that's actually 00:34:00.089 --> 00:34:03.670 pretty complicated and to do it right you need 00:34:03.670 --> 00:34:07.210 to spend time and do some research and and so 00:34:07.210 --> 00:34:10.630 on so it's even with the organizations that are 00:34:10.630 --> 00:34:14.250 trying to sort it out and are basing their regulations 00:34:14.250 --> 00:34:17.539 on The science we have at the moment, even these 00:34:17.539 --> 00:34:21.800 organizations are not perfect because it is so 00:34:21.800 --> 00:34:24.239 complicated and hard to do. Exactly. Yeah, well 00:34:24.239 --> 00:34:26.239 said. All right. Two short questions to finish. 00:34:26.380 --> 00:34:30.050 If you could make one. change in sports on the 00:34:30.050 --> 00:34:32.949 base of your research, previous or the research 00:34:32.949 --> 00:34:35.210 you do now, what would it be? I don't think that 00:34:35.210 --> 00:34:38.730 I have any specific change today or tomorrow 00:34:38.730 --> 00:34:41.590 that I would implement based off of what we know. 00:34:41.730 --> 00:34:45.090 But I do think that understanding that putting 00:34:45.090 --> 00:34:48.130 two thresholds, an SRY threshold and a testosterone 00:34:48.130 --> 00:34:52.210 threshold on performance is just a simplistic 00:34:52.210 --> 00:34:54.769 view. And I think it'd be good to appreciate 00:34:54.769 --> 00:34:58.389 the complexities. of sex development and how 00:34:58.889 --> 00:35:01.210 There's more to it than just those two things. 00:35:01.269 --> 00:35:04.349 So I think mainly it'd be to have the data supporting 00:35:04.349 --> 00:35:07.030 it. And so to have, I think I mentioned before, 00:35:07.070 --> 00:35:08.889 to have, again, there's nothing I would change 00:35:08.889 --> 00:35:10.429 today or tomorrow because we just don't have 00:35:10.429 --> 00:35:13.210 the data yet. But to be able to have the data 00:35:13.210 --> 00:35:15.889 and the evidence to choose a threshold for testosterone, 00:35:15.969 --> 00:35:20.010 to choose maybe a receptive level or sensitivity 00:35:20.010 --> 00:35:23.230 to the testosterone, and maybe to just have the 00:35:23.230 --> 00:35:26.590 information to support that threshold that whatever 00:35:26.590 --> 00:35:30.019 one gets ends up. getting chosen and you know 00:35:30.019 --> 00:35:32.539 if there are individuals that fall in between 00:35:32.539 --> 00:35:36.239 because of the sry test to have an avenue for 00:35:36.239 --> 00:35:38.440 them and for it not to be black and white for 00:35:38.440 --> 00:35:40.739 those individuals that don't fit into that black 00:35:40.739 --> 00:35:43.599 and white category so that they at least have 00:35:43.599 --> 00:35:45.780 some clarity but i think at the end of the day 00:35:45.780 --> 00:35:48.500 i feel like i'm very repetitive but at the end 00:35:48.500 --> 00:35:50.440 of the day like i don't have any specific changes 00:35:50.440 --> 00:35:53.619 i'd make i would just like to see things be supported 00:35:53.619 --> 00:35:58.679 by robust science and for that to be the driver 00:35:58.679 --> 00:36:03.320 and not for a political agenda or anything else. 00:36:03.519 --> 00:36:05.920 And not that I'm saying that that is what's happening, 00:36:06.019 --> 00:36:08.940 but just that it's hard for a scientist to see 00:36:08.940 --> 00:36:12.329 when... Decisions beforehand were made around 00:36:12.329 --> 00:36:16.909 the different thresholds and people studying 00:36:16.909 --> 00:36:18.949 endocrinology and knowing what we know, we're 00:36:18.949 --> 00:36:20.949 like, where are these thresholds coming from? 00:36:21.289 --> 00:36:25.989 The evidence to support it, especially the testosterone 00:36:25.989 --> 00:36:29.369 threshold, are pretty weak. So lower evidence 00:36:29.369 --> 00:36:31.969 -based decisions, guidelines, let's put it that 00:36:31.969 --> 00:36:35.079 way. All right, and the last. question to finish 00:36:35.079 --> 00:36:37.420 is where people can find you if they want to 00:36:37.420 --> 00:36:40.719 look at your research, get in touch, look what 00:36:40.719 --> 00:36:43.639 you're up to. I'm not very active, but I do have 00:36:43.639 --> 00:36:45.960 a LinkedIn account. That's my first and last 00:36:45.960 --> 00:36:49.159 name. And our research, I mean, anywhere that 00:36:49.159 --> 00:36:52.559 if you search Google Scholar or PubMed, then 00:36:52.559 --> 00:36:55.960 any peer reviewed publication. comes out there. 00:36:56.079 --> 00:36:58.559 So thank you so much, Shani. Huge pleasure to 00:36:58.559 --> 00:37:01.440 talk to you and thank you for agreeing to talk 00:37:01.440 --> 00:37:04.980 about the topic that is hot and very debated 00:37:04.980 --> 00:37:07.619 at the moment. Thank you. Thanks, Alex. It's 00:37:07.619 --> 00:37:09.159 been great again speaking with you.