Peggy T. Cohen-Kettenis

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline

Objective: To update the “Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline,” published by the Endocrine Society in 2009. Participants: The participants include an Endocrine Society‐appointed task force of nine experts, a methodologist, and a medical writer. Evidence: This evidence‐based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: Group meetings, conference calls, and e‐mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender‐dysphoric/gender‐incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the persons genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the persons affirmed gender. Hormone treatment is not recommended for prepubertal gender‐dysphoric/gender‐incongruent persons. Those clinicians who recommend gender‐affirming endocrine treatments—appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)—should be knowledgeable about the diagnostic criteria and criteria for gender‐affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender‐dysphoric/gender‐incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin‐releasing hormone agonists. Clinicians may add gender‐affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender‐affirming surgery in older adolescents. For adult gender‐dysphoric/gender‐incongruent persons, the treating clinicians (collectively) should have expertise in transgender‐specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender‐appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender‐affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

A network analysis of body satisfaction of people with gender dysphoria

In gender dysphoria (GD), much of the experienced distress results from body dissatisfaction. The current study analyzed the configuration of body satisfaction in trans men and women using network analysis. In total, 485 individuals diagnosed with GD from four European countries, applying for medical treatment, filled out the Body Image Scale for Transsexuals. A six-factor model reflecting different body areas was confirmed via confirmatory factor analysis. A further configuration of body satisfaction was modelled using correlation network analysis techniques in R. Genital dissatisfaction showed limited connection with other body areas in comparison to other subscales. Body characteristics influencing social gender recognition were most centrally involved in body (dis)satisfaction in both natal sexes. In trans women these characteristics were related mostly to voice and hair, whereas in trans men these characteristics were related to muscularity and posture. Focusing on these socially influential body characteristics may provide important targets for transgender healthcare.

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development

The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.

Gender Incongruence of Adolescence and Adulthood: Acceptability and Clinical Utility of the World Health Organization's Proposed ICD-11 Criteria.

The World Health Organization (WHO) is currently updating the tenth version of their diagnostic tool, the International Classification of Diseases (ICD, WHO, 1992). Changes have been proposed for the diagnosis of Transsexualism (ICD-10) with regard to terminology, placement and content. The aim of this study was to gather the opinions of transgender individuals (and their relatives/partners) and clinicians in the Netherlands, Flanders (Belgium) and the United Kingdom regarding the proposed changes and the clinical applicability and utility of the ICD-11 criteria of ‘Gender Incongruence of Adolescence and Adulthood’ (GIAA). A total of 628 participants were included in the study: 284 from the Netherlands (45.2%), 8 from Flanders (Belgium) (1.3%), and 336 (53.5%) from the UK. Most participants were transgender people (or their partners/relatives) (n = 522), 89 participants were healthcare providers (HCPs) and 17 were both healthcare providers and (partners/relatives of) transgender people. Participants completed an online survey developed for this study. Most participants were in favor of the proposed diagnostic term of ‘Gender Incongruence’ and thought that this was an improvement on the ICD-10 diagnostic term of ‘Transsexualism’. Placement in a separate chapter dealing with Sexual- and Gender-related Health or as a Z-code was preferred by many and only a small number of participants stated that this diagnosis should be excluded from the ICD-11. In the UK, most transgender participants thought there should be a diagnosis related to being trans. However, if it were to be removed from the chapter on “psychiatric disorders”, many transgender respondents indicated that they would prefer it to be removed from the ICD in its entirety. There were no large differences between the responses of the transgender participants (or their partners and relatives) and HCPs. HCPs were generally positive about the GIAA diagnosis; most thought the diagnosis was clearly defined and easy to use in their practice or work. The duration of gender incongruence (several months) was seen by many as too short and required a clearer definition. If the new diagnostic term of GIAA is retained, it should not be stigmatizing to individuals. Moving this diagnosis away from the mental and behavioral chapter was generally supported. Access to healthcare was one area where retaining a diagnosis seemed to be of benefit.

Surgical Satisfaction, Quality of Life, and Their Association After Gender-Affirming Surgery: A Follow-up Study.

ABSTRACT We assessed the outcomes of gender-affirming surgery (GAS, or sex-reassignment surgery) 4 to 6 years after first clinical contact, and the associations between postoperative (dis)satisfaction and quality of life (QoL). Our multicenter, cross-sectional follow-up study involved persons diagnosed with gender dysphoria (DSM-IV-TR) who applied for medical interventions from 2007 until 2009. Of 546 eligible persons, 201 (37%) responded, of whom 136 had undergone GAS (genital, chest, facial, vocal cord and/or thyroid cartilage surgery). Main outcome measures were procedure performed, self-reported complications, and satisfaction with surgical outcomes (standardized questionnaires), QoL (Satisfaction With Life Scale, Subjective Happiness Scale, Cantril Ladder), gender dysphoria (Utrecht Gender Dysphoria Scale), and psychological symptoms (Symptom Checklist-90). Postoperative satisfaction was 94% to 100%, depending on the type of surgery performed. Eight (6%) of the participants reported dissatisfaction and/or regret, which was associated with preoperative psychological symptoms or self-reported surgical complications (OR = 6.07). Satisfied respondents’ QoL scores were similar to reference values; dissatisfied or regretful respondents’ scores were lower. Therefore, dissatisfaction after GAS may be viewed as indicator of unfavorable psychological and QoL outcomes.

Does polycystic ovary syndrome affect cognition? A functional magnetic resonance imaging study exploring working memory

OBJECTIVE To study effects of overexposure to androgens and subsequent antiandrogenic treatment on brain activity during working memory processes in women with polycystic ovary syndrome (PCOS). DESIGN In this longitudinal study, working memory function was evaluated with the use of functional magnetic resonance imaging (MRI) in women with PCOS before and after antiandrogenic treatment. SETTING Department of reproductive medicine, university medical center. PATIENT(S) Fourteen women with PCOS and with hyperandrogenism and 20 healthy control women without any features of PCOS or other hormonal disorders. INTERVENTION(S) Antiandrogenic hormone treatment. MAIN OUTCOME MEASURE(S) Functional MRI response during a working memory task. RESULT(S) At baseline women with PCOS showed more activation than the control group within the right superior parietal lobe and the inferior parietal lobe during task (all memory conditions). Task performance (speed and accuracy) did not differ between the groups. After antiandrogenic treatment the difference in overall brain activity between the groups disappeared and accuracy in the high memory load condition of the working memory task increased in women with PCOS. CONCLUSION(S) Women with PCOS may need additional neural resources during a working memory task compared with women without PCOS, suggesting less efficient executive functioning. This inefficiency may have effects on daily life functioning of women with PCOS. Antiandrogenic treatment appears to have a beneficial effect on this area of cognitive functioning. CLINICAL TRIAL REGISTRATION NUMBER NTR2493.

Psychological functioning in adolescents referred to specialist gender identity clinics across Europe: a clinical comparison study between four clinics

Adolescents seeking professional help with their gender identity development often present with psychological difficulties. Existing literature on psychological functioning of gender diverse young people is limited and mostly bound to national chart reviews. This study examined the prevalence of psychological functioning and peer relationship problems in adolescents across four European specialist gender services (The Netherlands, Belgium, the UK, and Switzerland), using the Child Behavioural Checklist (CBCL) and the Youth Self-Report (YSR). Differences in psychological functioning and peer relationships were found in gender diverse adolescents across Europe. Overall, emotional and behavioural problems and peer relationship problems were most prevalent in adolescents from the UK, followed by Switzerland and Belgium. The least behavioural and emotional problems and peer relationship problems were reported by adolescents from The Netherlands. Across the four clinics, a similar pattern of gender differences was found. Birth-assigned girls showed more behavioural problems and externalising problems in the clinical range, as reported by their parents. According to self-report, internalising problems in the clinical range were more prevalent in adolescent birth-assigned boys. More research is needed to gain a better understanding of the difference in clinical presentations in gender diverse adolescents and to investigate what contextual factors that may contribute to this.

ENDOCRINE TREATMENT OF GENDER-DYSPHORIC/GENDER-INCONGRUENT PERSONS: AN ENDOCRINE SOCIETY* CLINICAL PRACTICE GUIDELINE

Wylie C. Hembree, Peggy T. Cohen-Kettenis, Louis Gooren, Sabine E. Hannema, Walter J. Meyer, M. Hassan Murad, Stephen M. Rosenthal, Joshua D. Safer, Vin Tangpricha, and Guy G. T’Sjoen New York Presbyterian Hospital, Columbia University Medical Center, New York, New York 10032 (Retired); VU University Medical Center, 1007 MB Amsterdam, Netherlands (Retired); VU University Medical Center, 1007 MB Amsterdam, Netherlands (Retired); Leiden University Medical Center, 2300 RC Leiden, Netherlands; University of Texas Medical Branch, Galveston, Texas 77555; Mayo Clinic EvidenceBased Practice Center, Rochester, Minnesota 55905; University of California San Francisco, Benioff Children’s Hospital, San Francisco, California 94143; Boston University School of Medicine, Boston, Massachusetts 02118; Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, Georgia 30322; and Ghent University Hospital, 9000 Ghent, Belgium