Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L-1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs.

A European Network for the Investigation of Gender Incongruence: Endocrine Part.

INTRODUCTION: Cross-sex hormone therapy is an essential part of gender affirming treatment of transgender individuals. Studies systematically describing the physical and psychological effects of hormonal treatment of transgender persons are scarce. AIM: The aim of the current protocol is to evaluate clinical and side-effects of cross-sex hormonal treatment in trans persons. METHODS: The European Network for the Investigation of Gender Incongruence (ENIGI) is a multicenter prospective study. Because of the relatively low prevalence of the condition and small number of specialized centers, international collaboration is warranted. Four European treatment centers, Ghent, Oslo, Florence, and Amsterdam, developed a common study and treatment protocol. MAIN OUTCOME MEASURES: Outcome measures include hormonal and metabolic parameters, bone density, secondary sex and anthropometric characteristics, and physical and psychological well-being. RESULTS: Thus far, 333 trans women and 343 trans men have been included in the ENIGI Endocrine protocol. The study is still ongoing. CONCLUSION: In recent years, the number of trans persons seeking gender affirming treatment has increased. However, well-designed prospective studies evaluating safety and effectiveness of current hormonal treatment protocols are lacking. Therefore we started the ENIGI collaboration. In this article we give a detailed description of the study protocol, objectives, and design of the ENIGI Endocrine protocol.

Oestrogens are Not Related to Emotional Processing: a Study of Regional Brain Activity in Female-to-Male Transsexuals Under Gonadal Suppression.

Although the prevailing opinion is that emotional processes are influenced by sex hormones, the literature is still inconclusive. The aim of the current study was to examine the effects of gonadal suppression on brain activity during affective picture processing. Twenty-one female-to-male (FtM) transsexuals and 19 control women were recruited and underwent functional magnetic resonance imaging scanning while rating emotional pictures adapted from the International Affective Picture System. The gonadal hormone production of the FtMs was suppressed for 8 weeks, the control group did not receive any treatment before scanning. Under gonadal suppression, FtMs showed less brain activation in the superior temporal lobe compared with female controls during perception of positive affective pictures. Regression analysis showed that during processing of positive affective images, brain activity within the right superior temporal lobe was not correlated with levels of estradiol, luteinizing hormone, and follicle-stimulating hormone. In the absence of associations with hormonal levels, the difference in activation in the superior temporal lobe during positive emotional stimuli between FtMs and control women may be attributed to a priori differences between the 2 groups. Future studies should clarify if these differences are a result of atypical sexual differentiation of the brain in FtMs.

Oct-4 expression in human endometrium.

The transcription factor Oct-4 is crucial for the maintenance of cell pluripotency and is known to be expressed in embryonic stem cells, germ cells and whole embryos at various stages of development. Oct-4 regulates cell fate in a dose-dependent manner and plays a key role in germ-cell tumours. In the past, several stem-cell markers have been detected, and their role in the pathogenesis of diseases has been discussed frequently. Thus, we investigated the expression of Oct-4 comparing its occurrence in endometrium of healthy and diseased women using immunohistochemistry (IHC) and RT-PCR. IHC demonstrated Oct-4 expression in 25 of 60 sections (42%), respectively in 11 out of 25 patients (44%). Oct-4 mRNA was detected by RT-PCR in all tested samples (9 of 9) of endometrium, although the levels of expression varied. To our knowledge, this is the first study demonstrating Oct-4 expression in human endometrium.

Diagnostic hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal patients.

The aim of this observational clinical study was to evaluate the feasibility and diagnostic accuracy of outpatient diagnostic hysteroscopy in premenopausal patients suffering from abnormal uterine bleeding. Between September 1996 and September 1999, 819 patients were referred to our outpatient hysteroscopy clinic, 317 of which were premenopausal, and presenting with menstrual symptoms. All hysteroscopies were performed using a standard 30 degrees 5-mm hysteroscope, and the uterine cavity was generally distended with normal saline. Hysteroscopy was completed successfully in 305 cases (96.2%), but since the routine use of lidocaine spray in 1998 this figure increased up to 98.9%. Intrauterine pathology was diagnosed in almost 34% of patients, the most frequent being submucous myomas (14%) and endometrial polyps (14%); there was no case of endometrial cancer in this subset of patients. Moreover, there was an age-related distribution of intrauterine pathology, with the highest incidence in patients aged 41-50 years. Diagnostic hysteroscopy is a simple and safe technique, well accepted by the vast majority of patients; due to its excellent diagnostic accuracy, and its high success rate as an outpatient procedure, we wonder why inpatient D&C under general anesthesia is still regarded a diagnostic or even therapeutic option for patients with abnormal uterine bleeding.