 A 22-year-old art student at the Royal Danish Academy of Fine Arts named Einar Wegner was married to his fellow student, 18-year-old Gerda Gottlieb, in 1904. The two of them worked together as successful commercial illustrators, sometimes also selling their paintings to patrons, eventually moving to Paris in 1912. Gerda saw some success as a portrait painter there, mostly of women, in an Art Nouveau style. One day, her model was late to the sitting, and she asked her husband Einar to fill in as a generic model, dressed in women's clothing, stockings and heels for a study of the female leg. For Einar, this was to be a moment of great importance. He suddenly felt right in his new clothing. Einar, with the support of his wife, began a new life as Lily Elbe. After decades of living as a woman, Lily was to be the second person to undergo gender reassignment surgery. In fact, it was a series of four surgeries over two years, 1930 and 1931, in Berlin and Dresden, removing the penis and scrotum and planting a uterus, ovary and the construction of a vagina. Elbe was able to change names and genders and get a dissolution of marriage from Gerda. In late 1931, complications around the transplantation of the uterus led to infection. In an era before antibiotics, and three months later, her death was from cardiac arrest secondary to the infection. As a bizarre intersection of history, the final, ultimately fatal surgery was performed by a card-carrying member of the Nazi Party, Dr. Kurt Vornikos, at the Dresden Women's Clinic. Most of the records would be lost in a book burning by Nazi students in 1933. The clinic itself, appropriated by the Nazi Party as an office building, would be obliterated in an Allied fire bombing in 1945. So many details of the case and the methods used are lost to history. Nevertheless, I think it's fair to say that transgenderism and gender reassignment surgery are modern, but not new. What I've noticed about the discussion around transgenderism is that it focuses on social normalization, sexual roles, cultural change, and psychology of dysphoria. But there's very little discussion about the medical merits of gender reassignment. What if we take out all the usual debate points about gender identity, pronouns, and whether transgender is a mental illness, and just focus entirely on whether people who undergo reassignment are healthier and happier afterwards, or whether, like Lily Elbe, it carries an element of unacceptable risk? Is it as a therapeutic medical procedure well indicated when examined in the same way that we might examine other controversial elected medical procedures, bariatric surgery for obesity, or mastectomy for cancer prevention, for example? As I mentioned, gender reassignment is hardly new, but the number of people who have undergone the procedure has grown in recent years. With more patients, we also see the possibility of systematic reviews of outcomes. I'm going to run through some key papers with links in the underbar. I'm not a medical doctor, and I would recommend anyone making medical decisions for themselves to consult a licensed healthcare professional. I want to start with an important paper in the journal Nature in 1995 by authors at the Netherlands Institute for Brain Research. Previous studies had established that the male and female brain differed in an area of the hypothalamus called the central bed nucleus of the striaterminalis, or BSTC. Hormones, like estrogen and testosterone, act on this region to change behaviors over time towards typically masculine or feminine norms. At an anatomical level, the BSTC in adult women is on average 44% smaller than the same region in adult men, something that's possible to observe in postmortem examinations. This 1995 study found that the brains of male to female transgenders, even those not on gender reassignment hormones, had female-sized BST regions. The authors then compared BST volumes in this group to non-transgender men who had their testes removed due to prostate cancer. Even though the cancer patient samples lacked male androgens, they still had male-sized BST regions. The authors concluded that this important sex-determining region of the brain is unlikely to be affected by changes in hormone level in adulthood, and more likely are acted on during development, which could mean non-specifically any time from conception to puberty. I offer this finding to establish that there is a good basis to believe that dysphoria has an organic medical cause rooted in brain biology. A young person finds that they are uncomfortable with their gender as a result of a mismatch in brain chemistry. This suggests two medical solutions. We can correct the disagreement in the gender of the brain or in the gender of the body. We're going to focus on the latter. How effective is gender reassignment in correcting this behavioral mismatch? Let's start with the impact of hormone therapy alone in the absence of surgical intervention. There's a recent systematic review by a British group that looked at 17 published studies of mental health and cross-sex hormonal interventions. The most common experimental design in these studies is the longitudinal survey. Participants are interviewed by a researcher with a standard survey at the time they're admitted to a program. That's the baseline reading. They're then re-interviewed post-treatment at various time points and the results are compared back to the baseline. An alternative design is to take random groups of patients from a post-treatment pool and compare them to a pre-treatment pool, which we could call a cross-sectional study. The advantage of the cross-section is that we can do it very quickly without having to track people over time, but it's more vulnerable to random differences in these populations. Because systematic reviews mix results from differently designed experiments, sometimes worth noting when they differ, as in this case. Almost all measures of mental health, anxiety, emotional quality of life, depression, dissociation, stress, self-esteem, show improvement in the longitudinal studies, the ones that follow individuals over time, but not always in the cross-sectional studies. That might suggest that these faster study designs are subject to unintended biases or are underpowered to detect the real effects, because the group of people who are getting cross-sex hormonal therapy are widely divergent. It's also not clear if the hormones themselves are having a directly positive effect on mental health, or by changing secondary sex characteristics like breast and hip size, beard and chest hair, which then lessens the sense of dysphoria or confusion, or it could even improve social interactions, as the way people treat the person transitioning changes with the changing secondary sex characteristics. Regardless, the effects on mental health are pretty clearly positive for a population of patients who are at high risk for mental health, substance abuse, self-harm, and suicide. Let's pause and review. Gender dysphoria seems to have a basis in a brain region associated with gendered behavior, possibly the result of hormonal effects early in development. Cross-sex hormone treatment seemed to be an effective way to reduce the symptoms of dysphoria, reducing anxiety, stress, dissociation, and depression, while increasing self-esteem and emotional quality of life. Beyond hormone treatments are gender reassignment surgeries, changing the appearance of genitalia and altering sexual function. The most common for male-to-female transition is an inversion of the penis. A 2012 review by a German group of 332 reassignment surgeries found the complications from the surgery were relatively low, with the exception of medial stenosis, which is a narrowing of the urinary entrance to the bladder, which was observed in 40% of patients, usually corrected easily with a second minor surgery. Wound healing disorders were observed in another 33% of patients, but that's a common complication for any invasive surgery. About one in 10 also experienced trouble with the new vaginal tissue, usually a narrowing or adhesion that could be corrected with additional surgery. So the procedure is relatively safe, but not without complications, some of them requiring additional procedures to correct, and every surgery carries with it some risk. How successful are they at treating dysphoria in conjunction with hormone therapy? There are fewer papers that break out the effects of gender reassignment surgery, but I want to contrast two in particular. One is on trans men and women in Denmark, and the other is on trans women in the US. The Danish study received survey responses from 148 transgender patients from a gender identity clinic with the aim of comparing differences in medical related quality of life measures between female-to-male and male-to-female transitions. The findings are interesting, with trans men being older, more likely to be divorced or widowed, and more likely to have sleep disturbance, likely as the result of testosterone treatments. It's this figure that I want to point out, though. These eight two-letter codes refer to scores on quality of life in areas like physical functioning, PF, sexual function, SF, mental health, MH. Here the comparisons are to the Dutch population in general, the control group. From this data it's fair to say that Dutch transgender people who have undergone reassignment and hormone therapy have roughly the same quality of life as any other person from the Netherlands, with the notable exception of sleep disturbance in trans men receiving testosterone. By contrast, a US-based study of 247 trans women found that those who underwent only hormone therapy generally had lower quality of life than the general population. Those who had the surgery fared better, and the group in the study with the best quality of life were those who also underwent facial feminization surgery, enlarging lips, raising cheekbones, rhinoplasty. In the US, it might be suggested in contrast to the Netherlands, passing for a woman had the biggest impact on quality of life. It could be that the more rigid attitudes in the US create a hostile environment, prevents gender reassignment from having the same therapeutic effect it does in the Netherlands. Alternatively, it could have to do with the challenge of finding healthcare in the US that understands or is willing to work with people undergoing transition, or the ambiguous legal status that transgender people have under US law. One final metric. Do people regret their surgical procedures later? One study of 49 Dutch trans men found that after an average of eight years, very few of those receiving gender reassignment were unsatisfied with the procedures. Most breved their procedures very favorably, and the reasons for dissatisfaction were mostly around complications of the surgery, permanent scarring or infections requiring second procedures. Most patients reported more frequent and more enjoyable sexual experiences, whether alone or with a partner, and family and work relationships were more stable than prior to the surgery. So, in conclusion, the evidence is fairly strong that most people who undergo gender reassignment surgery are happier with their choice years later and often see improvements in sexual enjoyment, psychological status, if they happen to limit a culture where they can access healthcare and legal protections. The surgery is relatively safe with some risk of complications, but no different than with many other invasive surgeries. It would appear to be an effective and safe therapy for people who experience dysphoria, so long as there's a proper vetting and qualification procedure in place. Whether transgenderism is a mental disorder or not, or whether you believe people who undergo reassignment should be treated one way or the other, are certainly points you can debate. What I don't think you can debate is that gender reassignment has a basis in therapeutic best practices and science-based medicine. Thanks for watching.