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Hormonal Treatment in Young People with Gender Dysphoria: a Systematic Review

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Hormonal Treatment in Young People with Gender Dysphoria: a Systematic Review Hormonal Treatment in Young Denise Chew, BBmed, a Jemma Anderson, MBBS, b Katrina Williams, MBBS, MSc, PhD, FRACP, FAFPHM, a, c, d PeopleTamara May, BA, BSc, GDipPsych,With PGDipPsych, Gender PhD, a, c, d, e Kenneth Dysphoria: Pang, MBBS, BMedSc, FRACP, PhD a, c, d, f, g A Systematic Review CONTEXT: abstract Hormonal interventions are being increasingly used to treat young people with gender dysphoria, but their effects in this population have not been systematically reviewed OBJECTIVE: before. To review evidence for the physical, psychosocial, and cognitive effects of gonadotropin-releasing hormone analogs (GnRHa), gender-affirming hormones, DATA SOURCES: antiandrogens, and progestins on transgender adolescents. We searched Medline, Embase, and PubMed databases from January 1, 1946, to STUDY SELECTION: June 10, 2017. We selected primary studies in which researchers examined the hormonal treatment of transgender adolescents and assessed their psychosocial, cognitive, and/or DATA EXTRACTION: physical effects. Two authors independently screened studies for inclusion and extracted data RESULTS: from eligible articles using a standardized recording form. n n n n Thirteen studies met our inclusionn criteria, in which researchers examined GnRHas ( = 9), estrogen ( = 3), testosterone ( = 5), antiandrogen (cyproterone acetate) ( = 1), and progestin (lynestrenol) ( = 1). Most treatments successfully achieved their intended physical effects, with GnRHas and cyproterone acetate suppressing sex hormones and estrogen or testosterone causing feminization or masculinization of secondary sex characteristics. GnRHa treatment was associated with improvement across multiple measures of psychological functioning but not gender dysphoria itself, whereas the psychosocial effects of gender-affirming hormones in transgender youth have not yet been LIMITATIONS: adequately assessed. CONCLUSIONS: There are few studies in this field and they have all been observational. Low-quality evidence suggests that hormonal treatments for transgender adolescents can achieve their intended physical effects, but evidence regarding their psychosocial and cognitive impact are generally lacking. Future research to address these knowledge gaps and improve understanding of the long-term effects of these treatments is required. Departments of aPediatrics and fPsychiatry, Melbourne Medical School, University of Melbourne, Parkville, Australia; bDiscipline of Paediatrics, Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide, Australia; cMurdoch Children’s Research Institute, Parkville, Australia; dThe Royal Children’s Hospital, Melbourne, Australia; eSchool of Psychology, Deakin University, Burwood, Australia; and gInflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia To cite: Chew D, Anderson J, Williams K, et al. Hormonal Treatment in Young People With Gender Dysphoria: A Systematic Review. Pediatrics. 2018;141(4):e20173742 Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 141, number 4, April 2018:e20173742 REVIEW ARTICLE – 10 12 Transgender is a term used to pulmonary embolism). Studies of Diagnosticas transgender and Statisticalor diagnosed Manual with describe an individual whose antiandrogens in transfemale adults ofGD Mental and/or Disorders, GID according Fourth to Edition the inner gender identity differs from have revealed that cyproterone Diagnostic and Statistical Manual of their sex assigned at birth. This acetate is able to reduce levels of Mental Disorders, Fifth Edition ; mismatch can cause distress and testosterone, whereas spironolactone International Classification of Diseases functional impairment, resulting in has a synergistic effect with estrogen ; or “ gender dysphoria (GD) or what was in improving both physical and ” 13 previously termed1, 2 gender identity hormonal outcomes. criteria. This age range was selected disorder (GID). to be consistent with the definition In contrast, studies of different Lancet of adolescence used by the recent Several hormonal treatment hormonal treatments in young Commission on Adolescent options are available for GD, the people with GD are scarce, meaning 16 Health. Studies were excluded if the appropriateness of which depends on that clinicians have often had to effects of hormonal therapy could not developmental stage. For instance, extrapolate from adult studies. This be separated from gender-affirming puberty can frequently exacerbate is problematic for several reasons. surgery, which could cause potential GD because of the development Firstly, adolescence is a period of issues related to interpretation of of unwanted secondary sexual rapid development across multiple 3 14 results. We included all published characteristics, which can be domains, and studies of hormonal study designs in any language, but reversibly suppressed by using treatments in adults with GD may conference abstracts or studies in gonadotropin-releasing hormone not readily translate to adolescents. 4, 5 which researchers failed to report analogs (GnRHas). In comparison, Secondly, some hormone treatments results at the group level with at least gender-affirming hormones (GAHs; used in young people with GD (eg, 10 individuals were excluded. also known as cross-sex hormonal GnRHas and progestins) are either Study Identification therapy) allow individuals to not commonly used in adults with actively masculinize or feminize GD or are used in adults for different their physical appearance to be reasons (eg, GnRHas for prostate 15 The Medline (Ovid) and Embase more consistent with their gender cancer). Finally, hormonal dosing (Ovid) databases were searched for identity. As GAHs are only partially regimens in adolescents with GD are references from January 1, 1946, to reversible, they are generally used frequently different from those used June 10, 2017, by using thesauri and/or only once an individual reaches in adults, which is likely to affect keywords. PubMed was searched the legal age of medical consent, outcomes. 5 by using keywords to retrieve which varies across countries. In Our purpose in this systematic electronic publications and items addition, antiandrogens, such as review is, therefore, to evaluate not indexed in Medline. The Medline spironolactone and cyproterone the currently available evidence search strategy was adapted for use acetate, can be used to counter the about the physical, psychosocial, in Embase and PubMed with the effects of testosterone in birth- “ 6, 7 and cognitive effects of different main search terms as follows: (GD or assigned male individuals, whereas ” hormonal therapies in transgender transsexualism or sexual and gender progestins, such as norethisterone youth. By doing so, we can directly disorders or transgender persons and medroxyprogesterone, are inform clinical practice involving this or gender identity), (drug therapy often employed to suppress menses population and highlight existing or therapeutic use or [hormonal in younger birth-assigned female knowledge gaps. or hormone*] or *steroids or exp individuals. METHODS gestagen or exp antiandrogen), Authors of multiple studies have and (adolescen* or pediatric* or investigated the physical and Eligibility Criteria pediatric* or youth* or teen or psychosocial effects of different teens or teenage*). Detailed search hormonal interventions in adults histories are available on request. with GD. GAHs have been examined Studies were considered eligible if Additional items were identified by most extensively, with authors of participants were given hormonal manually searching reference lists systematic reviews indicating that treatment (GnRHas, GAHs, of relevant retrieved articles. Two GAHs improve multiple aspects8, 9 of antiandrogens, or progestins) reviewers independently assessed psychosocial functioning, although and if analysis of psychosocial, all study titles and abstracts to they also increase serum triglycerides cognitive, and/or physical effects determine inclusion, with the full and risk of cardiovascular disease of these hormones were included. text being subsequently retrieved for (including venous thrombosis, Participants had to be younger potentially eligible studies to assess stroke, myocardial infarction, and than 25 years of age and described final suitability. Any disagreements Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 CHEW et al 19, 21,29 were resolved with discussion and conducted because individual and testosterone levels, consensus was reached for final outcome effect sizes were available although 1 study only revealed a Dataarticles. Extraction for a maximum of 2 studies. significant decrease in transfemale RESULTS adolescents (birth-assigned male individuals identifying as Study Selection 19 Two reviewers, working female individuals). There was independently and in duplicate, decreased testicular volume19, 21, 29in used a standardized form transfemale adolescents and The study selection process is to extract methodological, cessation of menses in transmale depicted in Fig 1. Eighty-three demographic, and outcome data. – – adolescents (birth-assigned female potentially relevant studies19 27, 29 were32 Data extracted included reported individuals identifying21 as male retrieved, of which 13 youth characteristics (number of individuals), although the latter met the inclusion criteria and participants pre- and posttreatment, often occurred after a withdrawal were systematically
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