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On Gender Dysphoria From DEPARTMENT OF CLINICAL NEUROSCIENCE Karolinska Institutet, Stockholm, Sweden ON GENDER DYSPHORIA Cecilia Dhejne Stockholm 2017 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Printed by Eprint AB 2017 © Cecilia Dhejne, 2017 ISBN 978-91-7676-583-8 On Gender Dysphoria THESIS FOR DOCTORAL DEGREE (Ph.D.) at Karolinska Institutet, to be publicly defended in lecture hall Nanna Svartz, Karolinska University Hospital Solna. Friday, March 31, 2017 at 9:00 a.m. By Cecilia Dhejne Principal Supervisor: Opponent: Professor Mikael Landén Ph.D., M.D. Annelou de Vries Karolinska Institutet VU University Medical Center Amsterdam Department of Medical Epidemiology and Department of Department of Child and Biostatistics, and Sahlgrenska Academy at Adolescent Psychiatry Gothenburg University, Institute of Neuroscience and Physiology Examination Board: Professor Olle Söder Co-supervisors: Karolinska Institutet Associate professor Stefan Arver Department of Women’s and Children’s Health Karolinska Institutet Division of Pediatric Endocrinology Department of Medicine, Huddinge Associate professor Owe Bodlund Ph.D. Katarina Görts Öberg Umeå University Karolinska Institutet Department of Clinical Science Department of Medicine, Huddinge Division of Psychiatry Professor emerita Sigbritt Werner Professor Johanna Adami Karolinska Institutet Sophiahemmet University Department of Medicine, Huddinge To mom and dad for not hindering my profite la vie attitude, for encouraging me to discover the world, and for always welcoming anyone and everyone to Sunday dinner. ABSTRACT Gender identity refers to an innate and deeply felt psychological identification as a female, male, or some other non-binary gender. Gender identity may be congruent or incongruent with the sex assigned at birth. Gender dysphoria refers to the discomfort or distress that gender incongruence may cause. If the distress is clinically significant, the individual may need gender-affirming treatment. The literature is sparse with respect to the etiology, prevalence, and long-term outcomes. The overall aim of this thesis is to further our understanding of gender dysphoria regarding neurobiological characteristics, epidemiology, and health following gender-affirming treatment. Study I explored the hypothesis that cerebral activation in hormone-naïve transgender women (assigned males at birth) on exposure to odorous steroids would be in line with their gender identity, and thus similar to cisgender women but different to cisgender men. Gender dysphoric transgender women demonstrated a cerebral activation pattern that corresponded predominately to that of cisgender females, but also some cisgender male characteristics. Study II described the prevalence and changes in incidence of applications for change of legal gender and applications to reverse the procedure during 1960- 2010. The incidence of gender dysphoria increased three times for individuals assigned male at birth, and two and half time times for individuals assigned female at birth. The increase accelerated after 2001. The rate of reversal applications was 2.2% with a significant decline over the study period. Study III explored long-term mortality and psychiatric morbidity after sex reassignment in a nation-wide cohort study (1973-2003). The overall mortality rate was higher in individuals who had undergone legal and medical transition compared with the general population for the whole period, but not for the period 1989-2003. Probands had more psychiatric inpatient care and suicide attempts compared with controls for the whole period as well as the period 1989-2003 (with the exception of suicide attempts). This study cannot determine the effectiveness of gender-affirming medical intervention, but the results highlight the need for better health care following gender transition. Study IV examined outcomes following legal and surgical gender transition, mean (SD) follow-up time 7.2 (7.3) years, by means of individual interviews with 16 men (assigned female at birth) and 49 women (assigned male at birth). The vast majority of the participants felt gender congruent and global clinically improved, but the prevalence of psychiatric morbidity and suicide attempts was high. Childhood adversities and adult stressful life events were common. Being born abroad, childhood adversities, and not being accepted by others in assigned gender predicted current psychiatric morbidity. SAMMANFATTNING En persons könsidentitet beskriver den inre upplevelsen av könstillhörighet. Den kan vara kvinnligt, manligt eller något ickebinärt kön. Könsinkongruens innebär att en persons könsidentitet inte stämmer överens med det kön som blev tilldelat vid födseln. Könsdysfori är det lidande som könsinkongruens ibland orsakar. I de fall lidandet är uttalat kan personer behöva könsbekräftande behandling. Bakgrunden till könsdysfori, hur vanligt det är och hur en person mår efter behandling är ofullständigt känt. Det övergripande syftet med denna avhandling var öka kunskapen om könsdysfori avseende neurobiologiska karakteristiska, epidemiologi och hälsa efter könsbekräftande behandling. Studie I undersökte om transkvinnor (personer som tillskrivits manligt kön vid födseln men identifierar sig som kvinnor) aktiverade hjärnan på liknande sätt som ciskvinnor eller cismän (cispersoner = personer utan könsinkongruens eller könsdysfori) när de exponeras för feromoner Transkvinnor uppvisade ett aktiveringsmönster mer likt ciskvinnor men med en del cismanliga drag. I studie II har vi beskrivit incidensen av ansökningar om ändring av juridiskt kön samt tillstånd för operation av könsorganen under 1960-2010. Vi undersökte även antalet ansökningar om återgång till det ursprungliga könet. Vi fann att incidensen ökade tre gånger för dem som tillskrivits manligt kön vid födseln och två och en halv gång för dem som tillskrivits kvinnligt kön. Ökningen var mest uttalad efter 2001. Av de som beviljats ändring av juridiskt kön ansökte 2,2 % om att få återgå till ursprungligt kön. Antalet ångeransökningar minskade signifikant under den senare delen av tidsperioden. I studie III undersöktes överlevnad och psykiatrisk sjuklighet i en nationell kohort av personer som bytt juridisk kön och genomgått kirurgisk könsbekräftande behandling mellan 1973-2003. För hela tidsperioden fann vi en förhöjd dödlighet och att vård för psykisk sjukdom och självmordsförsök var vanligare jämfört med befolkningskontroller. Under den studerade perioden sågs en minskning avseende dödlighet och vård för självmordsförsök, där de som bytt juridiskt kön inte skilde sig från kontrollerna för perioden 1989-2003. En förhöjd risk att ha vårdats för psykisk sjukdom kvarstod dock under hela perioden. Studien var inte designad för att avgöra om könsbekräftande behandling förbättrar utfallet men pekar på behovet av bättre omhändertagande av personer som genomgått könsbekräftande åtgärder. Studie IV undersökte utfallet efter genomgången könsbekräftande behandling. Uppföljningstiden var i genomsnitt (SD) 7,2 (7,3) år. Sexton män (personer som tillskrivits kvinnligt kön vid födseln) och 49 kvinnor (personer som tillskrivits manligt kön vid födseln) intervjuades. En klar majoritet rapporterade att de kände sig könskongruenta och generellt förbättrade. Trots detta var psykisk sjuklighet och tidigare självmordsförsök vanligt. Det var också vanligt att ha varit utsatt för negativa barndomsupplevelser (fysisk eller känslomässig misshandel och/eller sexuella övergrepp) och att i vuxen ålder varit utsatt för diskriminering, trakasserier samt fysiskt och sexuellt våld. Att inte vara född i Sverige, att ha utsatts för negativa barndomsupplevelser och att inte vara accepterad i sin könstillhörighet av omgivningen var riskfaktorer för psykisk sjuklighet. LIST OF SCIENTIFIC PAPERS I. Berglund, H., Lindström, P., Dhejne-Helmy, C., & Savic, I. (2008). Male-to female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cerebral Cortex, 18(8), 1900-1908. doi:bhm216 [pii]10.1093/cercor/bhm216 II. Dhejne, C., Öberg, K., Arver, S., & Landén, M. (2014). An analysis of all applications for sex reassignment surgery in Sweden, 1960-2010: prevalence, incidence, and regrets. Archives of Sexual Behavior, 43(8), 1535-1545. doi:10.1007/s10508-014-0300-8 III. Dhejne, C., Lichtenstein, P., Boman, M., Johansson, A. L., Långström, N., & Landén, M. (2011). Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PloS One, 6(2), e16885. doi:10.1371/journal.pone.0016885 IV. Dhejne, C., Öberg, K., Arver, S., Kardell, M., Werner, S., & Landén, M. Gender congruence and psychiatric morbidity after gender-affirming health care: Relation to childhood adversities and adult stressful life events. Manuscript. CONTENTS 1 Introduction ..................................................................................................................... 1 1.1 Terminology / language ........................................................................................ 2 1.2 Cultaral and historical remarks ............................................................................. 6 1.3 Medical background .............................................................................................. 7 1.4 Development of gender-affirming health care in Sweden ................................... 9 1.5 Legal gender recognition ....................................................................................
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