In this module, we will review the essential strategies for transgender hormone care, really focusing on the impact of androgens in those strategies. Upon completion of this module, you will be able to identify the impact of androgens on physical structures, and you will be able to outline the current strategy for transgender hormone therapy. A major input into the strategy for transgender hormone therapy is recognizing that presentation of transgender individuals in late adolescents or adulthood is more the norm than the exception. The problem is that without a blood test or a scan or any other objective way to determine if someone is transgender, we're dependent on that person being able to articulate, to tell us that they are a transgender. They need to be aware of gender identity, and they need to have the language in order to be able to explain that to us. Of course, that happens developmentally only over time and can result therefore in transgender individuals who are only able to do that after they have been through puberty and later adolescence or even in adulthood. One other point that I want to make that is relevant to thinking about the strategy of hormone therapy is fertility. With the technology that we have currently in medicine, our interventions, whether medical or surgical, interfere with fertility. What interventions we want to take relative to the relative risks to individuals fertility is an important concern that we need to deal with our patients, and for which they need to be advised even before they begin treatment. This picture from the Boston Globe from 2011 is up for me to present the impact of testosterone on physical structures. These are identical twins, and as I've previously mentioned, identical twins are not really identical. That's just a term. Really, they're just very similar. These two identical twins are both XY. But the one on your left, the girl, is a transgender girl. All that's happened to her as of the time that this picture was taken is that, she's received GnRH agonist, that is puberty blockers, and what that illustrates is that a typical female puberty and development is linear. That is to say, girls and women are simply older and older versions of themselves. By contrast, if you look at the non-transgender sibling, the sister's sibling, that is the boy on your right, you will see that male-identified individuals, boys, man, or anyone who is going to receive a large dose of testosterone from their body or from elsewhere at some juncture, are going to have an inflection point in terms of physical features, and look at the features on the boy. Above his lip, you see some hair growth, and that you might predict, but also look at midline structures. Look at his nose, which is already larger than hers, and this is probably less than a year of puberty, less than a year of testosterone exposure that's causing these results already. Look at his jaw, his mandible, which is already more squared because of that testosterone effect. Look at the larynx, which includes soft structures that are growing, and therefore, we can already anticipate that his voice must be deepening. You can see to the sides of his neck, the SCM muscles, they are larger. Because this is a known pair of children, we know that he was not a bodybuilder at the time this picture was taken. This is simply less than one year of testosterone impact on the muscles on the sides of his neck. The other element to understanding strategy with regard to hormones is to recognize that the big difference between men and women hormonally is testosterone. That is to say, estradiol levels, that is the female hormone, circulate at very similar levels in men and women. It's true that the female range is slightly above the male range, and you can see that in your clinical laboratories, but those ranges overlap, and that difference is not considered clinically significant. By contrast, men have as much as tenfold greater testosterone than women circulating. So, when we think about the strategy for pediatrics and adolescence, we are trying to avoid those permanent characteristics that I demonstrated in that picture. If we can, we have available to us for really young children, before there is any puberty, something that is called social transition, which is simply changing haircut or clothing or whatever it takes to appear in a way that fits gender identity, and we recognize that some young children will not be transgender in adulthood even though they reported that they were transgender when they were kids. While some worry that those numbers maybe large, we don't actually have any statistics, and I don't know that this is actually a large number of children. When we're talking about social transition, that is completely reversible, and so there's no fear for that. Clothes can be changed. Haircut can be changed. Because gender identity is biology, too, I can be reassuring to my patients that there isn't a fear either that the child will somehow be brainwashed to be transgender. We've failed to brainwash intersex individuals to change gender identity with a far more rigorous program than simply changing their haircut or their clothes. So the idea that we're going to now cause gender identity to change in other children seems very unlikely, and I think we can be reassuring to our patients on this point. For those kids who are beginning to enter puberty then, we can use GnRH agonists or puberty blockers to delay that puberty. As I said, for adolescents, we use GnRH agonist or puberty blockers. They are essentially reversible and considered quite safe. We've used them for years with an entity that is called precocious puberty. When kids go into puberty at a younger age, then we would consider to be normal. When we use puberty blockers for those kids, all that happens, is when they get to an age when puberty would be more appropriate, we discontinue that intervention, and puberty progresses normally. The fear with this sort of intervention, is that we depend on sex steroids for healthy bone. So if there are prolonged periods where we don't give sex steroids, whether they're female or male steroids, estrogen or testosterone, that there will be some long-term bone harm. With regard to the kids with precocious puberty, we know that when we check those individuals later in life, we cannot detect that bone harm, usually osteoporosis, their rates are not different from those of individuals who did not have those interventions. That is reassuring, but it could also mean that there just are not enough people with precocious puberty for us to have the best statistics on that subject. The only transgender specific study on the subject comes out of Europe, and it's this small study that I have up on the slide in front of you now. If you look all the way to the left of the slide at baseline and then to the middle bar, what you see are a decrease in what are, on this slide is Z-scores. The point of Z-scores when we're discussing bone health is that they are the circumstance for those kids relative to their peers. It's not that they're bone is getting worse, their bone is growing. It's just that they're falling behind their peers. At the middle bar, that is on GnRH agonists or puberty blockers, and then at the far right-hand side of the graph, is when sex steroids were introduced. The thing to note is that the transgender kids did not catch back up to their baseline when they got the sex steroids. That is, they continued to have that bone development which was behind their peers. There are many complaints with this study. It is small, the children treated were old, the hormone doses they received were low. However, it's the only study we have, and it is not reassuring. It does suggest that there is some concern with regard to bone health when we withhold sex steroids for a significant period of time, and the result therefore is that, for adolescents who are well established in their gender identity, that is an argument to begin transgender hormone treatment, that is sex steroids, even at earlier ages when we have the confidence to do so. With regard to adult transgender men, the strategy is very straightforward. All we're doing is adding testosterone to raise their levels from the female range to the male range. Really, the only thing beyond that to recognize is that androgen, that male hormone supplementation, can be lifelong. For adult transgender women, blockade to some degree of androgen production or action along with some degree of estrogen supplementation is required. Because remember, what we're really trying to do is decrease the testosterone. That said, people need some sex steroids, and so for those transgender women, we want to have some estrogen for them in order to protect bone health. The problem with regard to transgender women, is that estrogens are associated with blood clots, that is thrombosis, and so some of our strategies and our thought processes reflect these particular concerns. We'll discuss that in upcoming modules. So, in summary, testosterone has dramatic impact on physical structures. Puberty blockers can be used to pause puberty safely and reversibly The main difference hormonally between men and women is testosterone, and so the main take-home from this module is that, with regard to hormone strategy, manipulation of testosterone for both transgender men and for transgender women, is the key consideration. Thank you very much for your attention. In the next modules, we will go into more detail for both transmasculine hormone regimens and transfeminine regimens. Please join me.
