Executive summary: Quality standards of care units for people with sexual and gender diversity.

Comprehensive biopsychosocial care for people with gender incongruence (ICD 11) who are transgender (trans) or gender diverse is a complex process in which the quality of the medical transition can only be guaranteed after a multidisciplinary approach, through teams that integrate professionals with training and experience not only in medicine but also in diversity and gender identity. Based on this, the Gonad, Identity and Sexual Differentiation working group of the Spanish Society of Endocrinology and Nutrition (GT-GIDSEEN) has established minimum care requirements that aim to guarantee adequate health care for these people by professionals. A position paper has been produced and is available at https://www.seen.es/portal/documentos/estandares-calidad-gidseen-2024.

Evolution and trends in referrals to a specialist gender identity unit in Spain over 10 years (2012-2021).

BACKGROUND: International studies have reported an increase in referrals to gender identity units, a shift in the assigned sex ratio of adolescents, a decrease in the age at first visit, and a growing presence of individuals with nonbinary gender identities. AIM: To investigate whether these trends are present in a Spanish sample of individuals referred to a gender identity unit over the last 10 years. METHODS: We conducted a retrospective chart review of 913 consecutive referrals to a gender identity unit between 2012 and 2021 and retrieved information regarding sex assigned at birth, age at first visit, and expressed gender identity. We stratified the patients into 5 age categories: children (<12 years), adolescents (12-17 years), young adults (18-25 years), adults (26-45 years), and older adults (>45 years). The data were analyzed via descriptive and regression analyses. OUTCOMES: Outcomes included the number of annual referrals, age at first visit, assigned sex ratio, and individuals with nonbinary gender identities. RESULTS: The number of referrals increased 10-fold, from 18 in 2012 to 189 in 2021. The rates of increase over time were significantly more pronounced for adolescents and young adults and significantly greater for those assigned female at birth (AFAB). The age of referrals at first visit decreased, and AFAB individuals were, on average, younger than individuals assigned male at birth. The assigned sex ratio favored AFAB patients among adolescents (2.4:1) and young adults (1.75:1). Logistic regression showed that the odds of a new referral being AFAB increased by 9% per calendar year and that adolescent and young adult new referrals were significantly more likely to be AFAB. There were 21 referrals of nonbinary individuals starting in 2017, making up 6.4% of applications in 2021 and 2.9% during the last 5 years. CLINICAL IMPLICATIONS: The evolution and trends observed in this study highlight the need for expanded resources, competent care, and careful reflection about implications for best practice. STRENGTHS AND LIMITATIONS: This investigation involves a large sample of patients and is the first in our country to include people of all ages. However, the findings might not be generalizable to other gender identity units or the broader population of gender-diverse individuals. CONCLUSION: Overall, our findings were consistent with previous international reports. We observed a marked increase in referrals, particularly among AFAB adolescents and young adults, a decreased age at first visit, and a growing presence of nonbinary individuals.

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study.

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Clinical practice guidelines for transsexual, transgender and gender diverse minors.

Some people, including minors, have a gender identity that does not correspond to the sex assigned at birth. They are known as trans* people, which is an umbrella term that encompasses transgender, transsexual, and other identities not conforming to the assigned gender. Healthcare units for trans* minors require multidisciplinary working, undertaken by personnel expert in gender identity, enabling, when requested, interventions for the minor and their social-familial environment, in an individualized and flexible way during the gender affirmation path. This service model also includes hormonal treatments tailored as much as possible to the individual's needs, beyond the dichotomic goals of a traditional binary model. This guide addresses the general aspects of professional care of trans* minors and presents the current evidence-based protocol of hormonal treatments for trans* and non-binary adolescents. In addition, it details key aspects related to expected body changes and their possible side effects, as well as prior counselling about fertility preservation.

Medical detransition following transgender identity reaffirmation: two case reports.

Background Recently, increased social and scientific attention has been paid to gender detransition, a phenomenon in which individuals discontinue gender-affirming medical interventions (GAMI) aimed at alleviating gender dysphoria (GD). Yet, clinical knowledge of detransitioners and their experiences is still scarce. Case reports published in the literature suggest that both internal and external factors may influence this decision. Methods Two transgender individuals treated for GD at a gender identity unit presented with a desire to discontinue GAMI. A description of their clinical evolution is presented. Results Increased body satisfaction, self-esteem, self-acceptance, and self-empowerment with respect to their transgender identity were mentioned by the patients as reasons for discontinuing gender-affirming treatments. Coinciding factors included reduced GD, positive changes in social environments, better interpersonal functioning, and higher levels of psychological well-being in general. Conclusions Gender detransition is an under-researched phenomenon. These cases highlight the need for a more nuanced approach to gender-related clinical presentations, which involves providing individuals the opportunity to work on their social ecosystems and explore alternative options to manage GD before initiating GAMI.

Self-injurious and suicidal behaviour in a transsexual adolescent and young adult population, treated at a specialised gender identity unit in Spain.

INTRODUCTION: Nonsuicidal self-injury (NSSI) and suicidal behavior (SB) have a significant prevalence in transsexual people. The published data is confusing as it does not distinguish between ideation and realization, age groups, gender, or the degree of medical intervention. Their actual prevalence in Spain is unknown. OBJECTIVE: Our objective was to investigate the prevalence of NSSI behavior and SB in adolescents and young transsexual adults, differentiating between ideation and consummated behavior, prior to their receiving any type of gender-affirming medical treatment. MATERIAL AND METHODS: We retrospectively reviewed the medical history of a cohort of transsexual people aged between 10 and 35 years, treated at the Gender Identity Unit of the Valencian Community. We analyzed the data collected regarding the presence of four variables: NSSI ideation, NSSI behavior, ideas of suicide and suicide attempts, as well as differences according to age group and gender. RESULTS: The final sample consisted of 110 transsexual men and 90 transsexual women. Of these, 21% had made a suicide attempt, 50% had had suicidal ideas, 31% had a history of NSSI behavior and 35% had had NSSI ideas. No differences were found based on gender. Regarding age, subjects under 20 years of age presented a significantly higher prevalence regarding suicidal ideas compared to young adults (43% vs. 25%), while in the remaining variables, no statistically significant differences were found. CONCLUSIONS: The prevalence of a history of suicidal ideas and behavior in the Spanish adolescent and young transsexual population is significant and does not differ according to gender or age range. The prevalence of NSSI ideas and behavior differs and is more frequent in adolescent transsexuals.

Self-injurious and suicidal behaviour in a transsexual adolescent and young adult population, treated at a specialised gender identity unit in Spain. / Antecedentes de comportamientos autolesivos y autolíticos en población adolescente y adulta joven transexual, atendida en una unidad especializada en identidad de género en España.

INTRODUCTION: Nonsuicidal self-injury (NSSI) and suicidal behavior (SB) have a significant prevalence in transsexual people. The published data is confusing as it does not distinguish between ideation and realization, age groups, gender, or the degree of medical intervention. Their actual prevalence in Spain is unknown. OBJECTIVE: Our objective was to investigate the prevalence of NSSI behavior and SB in adolescents and young transsexual adults, differentiating between ideation and consummated behavior, prior to their receiving any type of gender-affirming medical treatment. MATERIAL AND METHODS: We retrospectively reviewed the medical history of a cohort of transsexual people aged between 10 and 35 years, treated at the Gender Identity Unit of the Valencian Community. We analyzed the data collected regarding the presence of four variables: NSSI ideation, NSSI behavior, ideas of suicide and suicide attempts, as well as differences according to age group and gender. RESULTS: The final sample consisted of 110 transsexual men and 90 transsexual women. Of these, 21% had made a suicide attempt, 50% had had suicidal ideas, 31% had a history of NSSI behavior and 35% had had NSSI ideas. No differences were found based on gender. Regarding age, subjects under 20 years of age presented a significantly higher prevalence regarding suicidal ideas compared to young adults (43% vs. 25%), while in the remaining variables, no statistically significant differences were found. CONCLUSIONS: The prevalence of a history of suicidal ideas and behavior in the Spanish adolescent and young transsexual population is significant and does not differ according to gender or age range. The prevalence of NSSI ideas and behavior differs and is more frequent in adolescent transsexuals.

Testosterone administration increases leukocyte-endothelium interactions and inflammation in transgender men.

OBJECTIVE: To evaluate the effect of testosterone treatment on metabolic and inflammation parameters and leukocyte-endothelium interactions in transgender men (TGM). DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): One hundred fifty-seven TGM. INTERVENTION(S): Administration of testosterone undecanoate (1,000 mg, intramuscular) every 12 weeks. MAIN OUTCOME MEASURE(S): Endocrine parameters, adhesion molecules (vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and E-selectin), proinflammatory cytokines interleukin-6, and tumor necrosis factor alpha were evaluated in serum before and after treatment using Luminex's xMAP technology. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear leukocytes were assessed by flow chamber microscopy. RESULT(S): Testosterone treatment led to an increase in leukocyte-endothelium interactions due to an increase in polymorphonuclear leukocytes rolling and adhesion and decreased rolling velocity. It also boosted levels of vascular cell adhesion molecule-1, E-selectin, interleukin-6, and tumor necrosis factor alpha. As expected, testosterone also produced a significant increase in free androgenic index, androstenedione, total testosterone, and atherogenic index of plasma and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol. CONCLUSION(S): Treatment of TGM with testosterone induces an increase in leukocyte-endothelium interactions and adhesion molecules and proinflammatory cytokines. These effects are a reason to monitor cardiovascular risk in these patients.

[New care models for transgender people in the Spanish Health System: demands, controversies and reflections.] / Nuevos modelos de atención sanitaria para las personas transgénero en el Sistema Sanitario Español: demandas, controversias y reflexiones.

Health care for transgender people in Spain has been progressively established since 1999 when the first multidisciplinary unit for the treatment of sex reassignment was created in Andalusia. In this document, the social changes, the demands and debates of users and professionals, the new models of health care for trans people, and reflections on the current situation, have been analysed. The social openness in Spain regarding sexual and gender diversity has evolved quite positively. The health demands of the transgender users are not uniform and do not always match with the criteria of the professionals. In some Spanish regions, health care is distancing itself from the internationally recommended multidisciplinary model. The new healthcare models have been established under the aegis of primary care and/or endocrinologist in the area, without a required psychological assessment. The main contributing factors for this change of model have been the pressure from some associations with demands for "depathologization" and "decentralization". The professionals of gender units, while recognizing the need for a broader vision of trans reality, warn of the risk of treating trans people without the involvement of mental health specialists or by professionals in proximity with little experience. Moreover, the decentralization would not allow acting on large cohorts, which hinders the advance of knowledge and contrasted evaluations with neighbouring countries. In summary, the new health models, although intended to facilitate care through proximity, do not guarantee improvements in quality and difficult to make a comparative evaluation of the results.

La atención sanitaria a las personas transgénero en España se ha establecido de manera progresiva desde 1999, año en que Andalucía crea la primera unidad multidisciplinar para el tratamiento integral de la reasignación de sexo. Este documento analiza los cambios sociales, las demandas y debates entre usuarios y profesionales y los nuevos modelos de atención sanitaria, y también plantea reflexiones sobre la situación actual. La apertura social en España en la concepción de la diversidad sexual y de género es bastante favorable. Las demandas de los usuarios no son uniformes y no siempre coinciden con los criterios de los profesionales. En algunas comunidades autónomas la asistencia sanitaria se está distanciando del modelo recomendado internacionalmente, que basa la atención en equipos especializados o Unidades de Identidad de Género (UIG). Estos nuevos modelos centran la asistencia en la Atención Primaria, además de en endocrinólogos y pediatras de área sin una evaluación coordinada con Salud Mental. Los principales factores contribuyentes al cambio reciente han sido las demandas desde algunas asociaciones de "despatologización" y "descentralización". Estos nuevos modelos centran la asistencia en la Atención Primaria, además de en endocrinólogos y pediatras de área sin una evaluación coordinada con Salud Mental. Los profesionales que integran las unidades de género, si bien reconocen la necesidad de una visión amplia de la realidad transgénero, alertan del riesgo que supone tratar a personas trans sin una colaboración de especialistas en Salud Mental o por profesionales de área con escasa experiencia. Además, anticipan que la descentralización no facilita el estudio de grandes cohortes, dificultando el avance del conocimiento y la evaluación contrastada con países del entorno. En resumen, los nuevos modelos sanitarios, aunque ofrecen la atención en proximidad, no garantizan mejoras en la calidad ni promueven el análisis comparado de los resultados.

Transsexuality: Transitions, detransitions, and regrets in Spain. / Transexualidad: transiciones, detransiciones y arrepentimientos en España.

INTRODUCTION: Health care demand by transsexual people has recently increased, mostly at the expense of young and adolescents. The number of people who report a loss of or change in the former identity feeling (identity desistance) has also increased. While these are still a minority, we face more and more cases of transsexual people who ask for detransition and reversal of the changes achieved due to regret. OBJECTIVE: To report our experience with a group of transsexual people in detransition phase, and to analyze their personal experience and their associated conflicts. MATERIAL AND METHODS: A cohort of 796 people with gender incongruence attending the Identity Gender Unit of Doctor Peset University Hospital from January 2008 to December 2018 was studied. Four of the eight documented cases of detransition and/or regret are reported as the most representative. RESULTS: Causes of detransition included identity desistance, non-binary gender variants, associated psicomorbidities, and confusion between sexual identity and sexual orientation. CONCLUSION: Detransition is a growing phenomenon that implies clinical, psychological, and social issues. Inadequate evaluation and use of medicalization as the only means to improve gender dysphoria may lead to later detransition in some teenagers. Comprehensive care by a multidisciplinary and experienced team is essential. As there are no studies reporting the factors predictive of detransition, caution is recommended in cases of atypical identity courses.

Influence of obesity on atherogenic dyslipidemia in women with polycystic ovary syndrome.

BACKGROUND: Obesity is known to underlie, at least partially, dyslipidemia in polycystic ovary syndrome (PCOS), but it is unclear whether PCOS status per se increases the risk of alterations of lipoprotein subfractions, which differ in size and atherogenic potential. Our objective was to evaluate whether PCOS influences lipoprotein profile and LDL and HDL subfractions and to study the impact of obesity on these parameters. MATERIALS AND METHODS: This was a case-control study conducted in an academic medical centre. The study population consisted of 54 women of fertile age with PCOS and 60 controls adjusted for age and BMI. Biochemical lipid profile and LDL and HDL lipoprotein subfractions (measured using Lipoprint System). RESULTS: Lean PCOS women exhibited lower HDL cholesterol and apolipoprotein AI levels than controls, although these differences were not associated with alterations of lipoprotein subfractions. All obese subjects, whether PCOS or controls, displayed lipid parameters typical of atherogenic dyslipidemia, although the former group had lower levels of large HDL, higher levels of small HDL subfractions and a higher percentage of VLDL than the latter. These differences were associated with a greater prevalence of non-A LDL pattern (25.0%) in obese PCOS subjects than in obese controls (4.3%). CONCLUSIONS: PCOS does not constitute an additional risk factor for cardiovascular disease in lean women, but leads to a lipid profile characteristic of atherogenic dyslipidemia and an altered pattern of lipoprotein subfraction when associated with obesity.

Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual.

Transsexualism is defined as a strong conviction of belonging to the opposite sex in individuals without any physical intersex condition. Cross-sex hormone therapy is an important component of medical treatment of transexuals but it is not exempt from adverse effects. We report a case of a meningioma in a male-to-female transsexual patient treated with estrogens and cyproterone acetate for the past 4 years. He claimed recently severe headache and visual impairment. Blood tests showed normal results. A contrast-enhanced magnetic resonance imaging (MRI) scan revealed a mass in the tuberculum sellae consistent with a meningioma. Treatment was discontinued and tumor resection was performed. Histologic diagnosis confirmed strongly progesterone receptor-positive and estrogen negative meningioma. After surgery, the patient rejected the possibility of continuing with the treatment of estrogens and cyproterone, and so triptorelin (GnRH agonist) was initiated. At 1-year follow-up the patient's symptoms had ameliorated and a MRI scan revealed no recurrence of the tumor. This is the third case reported in the literature of a meningioma after treatment with estrogens and cyproterone acetate. We consider extremely important a long-term follow-up observation of male-to-female transsexual undergoing cross-sex hormone therapy in order to detect as soon as possible the adverse effects that can be derived from this therapy.

Prolactinoma induced by estrogen and cyproterone acetate in a male-to-female transsexual.

OBJECTIVE: To report a case of a microprolactinoma in a male-to-female transsexual treated with estrogens and cyproterone acetate. DESIGN: Case report. SETTING: Endocrinology unit in a university hospital. PATIENT(S): A 33-year-old male-to-female transsexual with prolactin level of 10 ng/mL. INTERVENTION(S): Treatment with equine-conjugated estrogens (2.5 mg/day, orally) and cyproterone acetate (100 mg/day, orally) during 6 months. MAIN OUTCOME MEASURE(S): Her levels of prolactin were repeatedly found to be elevated to a maximum of 133 ng/mL, and magnetic resonance imaging (MRI) revealed a pituitary mass of 5x4x4 mm. RESULT(S): Discontinuation of the cross-sex hormone treatment did not reduce the levels of prolactin. The use of dopaminergic-agonist therapy normalized them and reduced the size of the microadenoma. After sex-reassignment surgery, she was treated with low-dose estradiol transdermal patches and presented normal levels of prolactin and appropriate levels of 17beta-estradiol and testosterone with a stable image in MRI. CONCLUSION(S): We report a case of prolactinoma after treatment with equine-conjugated estrogens and cyproterone acetate. We recommend long-term follow-up observation consisting of a periodic evaluation of prolactin levels and any symptoms suggestive of hyperprolactinemia to detect as early as possible complications derived from cross-sex hormone therapy.

A novel mutation in DAX1 (NR0B1) causing X-linked adrenal hypoplasia congenita: clinical, hormonal and genetic analysis.

The association of primary adrenal insufficiency and hypogonadotropic hypogonadism is extremely infrequent in daily clinical practice. Differential diagnosis includes X-linked adrenal hypoplasia congenita, a genetic disease characterized by an alteration in the formation of the adrenal glands and the hypothalamus-pituitary-gonadal axis. The gene responsible is DAX1 (NR0B1). The most common form of clinical presentation is neonatal primary adrenal insufficiency and complete hypogonadotropic hypogonadism. Members of a single family often present the same clinical form, although there may be relatives affected with different clinical symptoms. The aim of this study is to characterize clinically and genetically a family affected by different forms of hypogonadotropic hypogonadism and/or primary adrenal insufficiency. We describe a family with three members affected, two adults and a neonate. The way of presentation of the adults was neonatal primary adrenal insufficiency and hypogonadotropic hypogonadism (one complete and another presenting as interrupted puberty). The genetic study revealed a new mutation in DAX1, p.Q76X gene (c.C226T), resulting in a truncated protein of 76 amino acids, the same in all three affected male patients and in the asymptomatic women of the family. These cases further expand the number of DAX1 mutations reported, as well as the description of infrequent forms of presentation of this disease as interrupted puberty.

Parameters of inflammation in morbid obesity: lack of effect of moderate weight loss.

BACKGROUND: Obesity has been associated with a chronic activation of the acute-phase response. The aims of our study were to investigate whether levels of inflammatory cytokines are higher in obese patients, to evaluate their relationship with metabolic syndrome, and to analyze the effect of moderate weight loss upon their levels. METHODS: Sixty-seven severe or morbid obese patients were compared with 67 controls. Patients were submitted to a 4-week very low calorie diet followed by a low calorie diet for 2 months. Exclusion criteria were organic disease, ischemic heart disease or stroke, diabetes mellitus, hyperlipidemia, and hypertension. An evaluation was performed before and after the diet, in which fibrinogen, blood count, high-sensitive C-reactive protein (CRP), interleukin 6 (IL-6), and tumoral necrosis factor alpha (TNF-alpha) were measured. The Student t test was employed to compare differences between the groups and Pearson correlation coefficients were calculated. RESULTS: Obese patients showed higher levels of CRP (P < 0.001), IL-6 (P < 0.001), TNF-alpha (P < 0.001), leukocyte (P = 0.001), and neutrophil count (P < 0.001) than controls. In obese patients, inflammatory parameters were significantly correlated with anthropometric parameters and did not differ between obese subjects with or without metabolic syndrome. Moderate weight loss (excess weight loss 19.6%) was achieved through dieting, but no change was observed in any inflammatory parameter. CONCLUSIONS: Obesity is associated to a chronic inflammatory state that seems to be due to an increased secretion of cytokines, and this state is not related to the presence of metabolic syndrome. Moderate weight loss does not ameliorate this inflammatory state in the short term.