Gender minority stress in transgender people: a major role for social network.

BACKGROUND: Gender minority individuals, on average, experience higher rates of mental health problems. Mounting work suggests that gender minority stress (GMS) contributes to mental health outcomes in transgender/gender-nonconforming individuals. AIM: We assessed whether GMS decreased in transgender people after initiating gender-affirming hormone therapy (GAHT), and we identified social predictors and hormonal associations for GMS at 2 time points. METHODS: GMS was surveyed through self-report questionnaires tapping into proximal and distal stressors and coping constructs following the minority stress framework. Eighty-five transgender persons wishing to undertake hormonal interventions were assessed prospectively at start of GAHT and after 7.7 ± 3.5 months (mean ± SD). Sixty-five cisgender persons served as a control group. OUTCOMES: (1) Proximal stressors were surveyed by the Beck Depression Inventory II, State-Trait Anxiety Inventory, Scale for Suicide Ideation, Suicidal Thoughts/Attempts, Stigma Consciousness Questionnaire, and Perceived Stress Scale; (2) distal stressors by the Everyday Discrimination Scale; and (3) coping constructs by the Resilience Scale, social network, social standing, and Marlowe Crowne Social Desirability Scale. RESULTS: Transgender people experienced higher rates of proximal stressors (Beck Depression Inventory II, State-Trait Anxiety Inventory, Scale for Suicide Ideation, Suicidal Thoughts/Attempts, Perceived Stress Scale) and had lower protective factors (social standing) prior to and during GAHT than cisgender people. Social network and resilience were lower in transgender people relative to cisgender peers only at baseline. Prospectively, decreasing trait anxiety was observed in transgender people. Social factors were adequate predictors of multiple GMS constructs. Specifically, a major role for social network emerged. As for hormonal associations, only serum estradiol levels in transgender women with GAHT were negatively associated with trait anxiety and suicidal thoughts/attempts but positively with resilience and social desirability. CLINICAL IMPLICATIONS: Stimulating a social environment supportive of diverse identities, particularly by investing in social networks as a resource for resilience, is likely to alleviate GMS. STRENGTHS AND LIMITATIONS: Longer duration of interventions with sex steroid treatment, with continued resilience-enhancing strategies, is needed to observe further alleviation of GMS in transgender persons. Also, objective and subjective GMS identification with heteronormative attitudes and beliefs should be surveyed for good measure when assessing GMS. CONCLUSION: Transgender people experienced more GMS throughout study visits than cisgender people did. With a relatively short period of GAHT, some significant changes in and predictors for experienced GMS emerged.

The association between newborn cord blood steroids and ambient prenatal exposure to air pollution: findings from the ENVIRONAGE birth cohort.

Knowledge of whether prenatal exposure to ambient air pollution disrupts steroidogenesis is currently lacking. We investigated the association between prenatal ambient air pollution and highly accurate measurements of cord blood steroid hormones from the androgenic pathway.This study included 397 newborns born between the years 2010 and 2015 from the ENVIRONAGE cohort in Belgium of whom six cord blood steroid levels were measured: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone, androstenedione, and testosterone. Maternal ambient exposure to PM2.5 (particles with aerodynamic diameter ≤ 2.5 µm), NO2, and black carbon (BC) were estimated daily during the entire pregnancy using a high-resolution spatiotemporal model. The associations between the cord blood steroids and the air pollutants were tested and estimated by first fitting linear regression models and followed by fitting weekly prenatal exposures to distributed lag models (DLM). These analyses accounted for possible confounders, coexposures, and an interaction effect between sex and the exposure. We examined mixture effects and critical exposure windows of PM2.5, NO2 and BC on cord blood steroids via the Bayesian kernel machine regression distributed lag model (BKMR-DLM).An interquartile range (IQR) increment of 7.96 µg/m3 in PM2.5 exposure during pregnancy trimester 3 was associated with an increase of 23.01% (99% confidence interval: 3.26-46.54%) in cord blood levels of 17α-hydroxypregnenolone, and an IQR increment of 0.58 µg/m³ in BC exposure during trimester 1 was associated with a decrease of 11.00% (99% CI: -19.86 to -0.012%) in cord blood levels of androstenedione. For these two models, the DLM statistics identified sensitive gestational time windows for cord blood steroids and ambient air pollution exposures, in particular for 17α-hydroxypregnenolone and PM2.5 exposure during trimester 3 (weeks 28-36) and for androsterone and BC exposure during early pregnancy (weeks 2-13) as well as during mid-pregnancy (weeks 18-26). We identified interaction effects between pollutants, which has been suggested especially for NO2.Our results suggest that prenatal exposure to ambient air pollutants during pregnancy interferes with steroid levels in cord blood. Further studies should investigate potential early-life action mechanisms and possible later-in-life adverse effects of hormonal disturbances due to air pollution exposure.

Gender-affirming hormone therapy: An updated literature review with an eye on the future.

In line with increasing numbers of transgender (trans) and gender nonbinary people requesting hormone treatment, the body of available research is expanding. More clinical research groups are presenting data, and the numbers of participants in these studies are rising. Many previous review papers have focused on all available data, as these were scarce, but a more recent literature review is timely. Hormonal regimens have changed over time, and older data may be less relevant for today's practice. In recent literature, we have found that even though mental health problems are more prevalent in trans people compared to cisgender people, less psychological difficulties occur, and life satisfaction increases with gender-affirming hormone treatment (GAHT) for those who feel this is a necessity. With GAHT, body composition and contours change towards the affirmed sex. Studies in bone health are reassuring, but special attention is needed for adolescent and adult trans women, aiming at adequate dosage of hormonal supplementation and stimulating therapy compliance. Existing epidemiological data suggest that the use of (certain) estrogens in trans women induces an increased risk of myocardial infarction and stroke, the reason that lifestyle management can be an integral part of trans health care. The observed cancer risk in trans people does not exceed the known cancer-risk differences between men and women. Now it is time to integrate the mostly reassuring data, to leave the overly cautious approach behind, to not copy the same research questions repeatedly, and to focus on longer follow-up data with larger cohorts.

Minority Stress and the Effects on Emotion Processing in Transgender Men and Cisgender People: A Study Combining fMRI and 1H-MRS.

BACKGROUND: Minority stress via discrimination, stigmatization, and exposure to violence can lead to development of mood and anxiety disorders and underlying neurobiochemical changes. To date, the neural and neurochemical correlates of emotion processing in transgender people (and their interaction) are unknown. METHODS: This study combined functional magnetic resonance imaging and magnetic resonance spectroscopy to uncover the effects of anxiety and perceived stress on the neural and neurochemical substrates, specifically choline, on emotion processing in transgender men. Thirty transgender men (TM), 30 cisgender men, and 35 cisgender women passively viewed angry, neutral, happy, and surprised faces in the functional magnetic resonance imaging scanner, underwent a magnetic resonance spectroscopy scan, and filled out mood- and anxiety-related questionnaires. RESULTS: As predicted, choline levels modulated the relationship between anxiety and stress symptoms and the neural response to angry and surprised (but not happy faces) in the amygdala. This was the case only for TM but not cisgender comparisons. More generally, neural responses in the left amygdala, left middle frontal gyrus, and medial frontal gyrus to emotional faces in TM resembled that of cisgender women. CONCLUSIONS: These results provide first evidence, to our knowledge, of a critical interaction between levels of analysis and that choline may influence neural processing of emotion in individuals prone to minority stress.

Osteoporosis and Bone Health in Transgender Individuals.

This review discusses the changes in bone mass, structure, and metabolism that occur upon gender-affirming hormonal treatment (GAHT) in transgender adults and adolescents, as well as their clinical relevance. In general, available evidence shows that GAHT in transgender adults is not associated with major bone loss. In transgender adolescents, pubertal suppression with gonadotropin-releasing hormone agonist monotherapy impairs bone development, but at least partial recovery is observed after GAHT initiation. Nevertheless, a research gap remains concerning fracture risk and determinants of bone strength other than bone mineral density. Attention for bone health is warranted especially in adult as well as adolescent trans women, given the relatively high prevalence of low bone mass both before the start of treatment and after long-term GAHT in this population. Strategies to optimize bone health include monitoring of treatment compliance and ensuring adequate exposure to administered sex steroids, in addition to general bone health measures such as adequate physical activity, adequate vitamin D and calcium intake, and a healthy lifestyle. When risk factors for osteoporosis exist the threshold to perform DXA should be low, and treatment decisions should be based on the same guidelines as the general population.

Gender Affirming Medical Treatment Desire and Treatment Motives in Binary and Non-Binary Transgender Individuals.

BACKGROUND: It is currently unknown whether there are differences in desire for gender affirming medical treatment (GAMT) between binary and non-binary transgender individuals, although the latter seek treatment less prevalently. AIM: To investigate differences between binary and non-binary individuals on received GAMT, desire for GAMT, and motives for (not) wanting GAMT, and to explore the association between having an unfulfilled treatment desire and general and sexual well-being. METHODS: We conducted an online questionnaire in a community sample of 125 transgender men, 72 transgender women, and 62 non-binary transgender individuals (age: M = 30.4, SD = 11.31, range 18-69). OUTCOME MEASURES: Undergone GAMT, GAMT desire, motives for (not) wanting (further) GAMT, Utrecht Gender Dysphoria Scale, Satisfaction With Life Scale, Hospital Anxiety and Depression Scale, Global Measure of Sexual Satisfaction, transgender-specific body image worries, and sexual self-concept discrepancies. RESULTS: Binary transgender participants reported having undergone more GAMT procedures than non-binary transgender participants (P < .001 for both gender affirming hormone treatment (GAHT) and gender affirming surgery (GAS)). While binary participants reported a stronger desire for GAHT compared to non-binary participants (X2(1, N = 93) = 32.63, P < .001), the groups did not differ in their desire for GAS (X2(1, N = 247) = 0.68, P = .411). Binary and non-binary participants reported similar reasons for wanting treatment, mostly related to body and/or gender incongruence and gender affirmation. In terms of not wanting treatment, the non-binary group reported their gender identity as the most important reason, while the binary group mostly mentioned possible medical complications. The majority of both groups had an unfulfilled treatment desire (69% of binary participants and 64.5% of non-binary participants), which was related to lower levels of general life satisfaction (P < .001) and sexual satisfaction (P = .005), more anxiety (P = .006) and transgender-specific body image worries (P < .001), and larger sexual self-concept discrepancies (P < .001 for actual and/or ideal, P < .001 for actual and/or ought). CLINICAL IMPLICATIONS: Systemic barriers to GAMT (especially GAS) should be removed not only for binary but also for non-binary identifying transgender individuals to decrease the discrepancy between treatment desire and actually seeking treatment. STRENGTHS & LIMITATIONS: This study was the first to systematically investigate differences in treatment desire motives between binary and non-binary transgender individuals, while also showing the possible negative consequences of an unfulfilled treatment desire. Given the online character of the study, results may not generalize to the broader transgender community. CONCLUSION: Similarly to binary transgender individuals, many non-binary transgender individuals have a desire for GAMT, and not being able to receive GAMT has a negative effect on their mental and sexual health. Further efforts should be made to make GAMT accessible for all transgender individuals, regardless of gender identity. Kennis M, Duecker F, T'Sjoen G, et al. Gender Affirming Medical Treatment Desire and Treatment Motives in Binary and Non-Binary Transgender Individuals. J Sex Med 2022;19:1173-1184.

In patients with controlled acromegaly, indices of glucose homeostasis correlate with IGF-1 levels rather than with type of treatment.

OBJECTIVE: Acromegaly is accompanied by abnormalities in glucose and lipid metabolism which improve upon treatment. Few studies have investigated whether these improvements differ between treatment modalities. This study aimed to compare glucose homeostasis, lipid profiles and postprandial gut hormone response in patients with controlled acromegaly according to actual treatment. DESIGN: Cross-sectional study at a tertiary care centre. PATIENTS: Twenty-one patients with acromegaly under stable control (ie insulin growth factor 1 [IGF1] levels below sex- and age-specific thresholds and a random growth hormone level <1.0 µg/L) after surgery (n = 5), during treatment with long-acting somatostatin analogues (n = 10) or long-acting somatostatin analogues + pegvisomant (n = 6) were included. MEASUREMENTS: Glucose, insulin, total cholesterol and high-density lipoprotein-cholesterol were measured in fasting serum samples. Glucose, insulin, triglycerides, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were measured during a mixed meal test. Insulin sensitivity was evaluated by a hyperinsulinaemic-euglycaemic clamp. RESULTS: There were no significant differences in glucose tolerance, insulin sensitivity or postprandial gut hormone responses between the three groups. Positive correlations between IGF1 levels and HbA1c, fasting glucose and insulin levels and postprandial area under the curve (AUC) of glucose and insulin and also an inverse association between IGF1 and glucose disposal rate were found in the whole cohort (all p < .05, lowest p = .001 for postprandial AUC glucose with rs  = 0.660). CONCLUSION: In this cross-sectional study in patients with controlled acromegaly, there were no differences in glucose homeostasis or postprandial substrate metabolism according to treatment modality. However, a lower IGF1 level seems associated with a better metabolic profile.

Characterisation of testicular function and spermatogenesis in transgender women.

STUDY QUESTION: Does gender-affirming treatment prevent full spermatogenesis in transgender women (TW)? SUMMARY ANSWER: Adequate hormonal therapy (HT) leads to complete suppression of spermatogenesis in most TW, if serum testosterone levels within female reference ranges are obtained. WHAT IS KNOWN ALREADY: Gender-affirming treatment in transgender individuals may involve gender-affirming HT. The effects on spermatogenesis in TW remain unclear. In order to add information from a referral centre for transgender care, we wish to compare results of earlier studies with our population of TW who received a standard hormone treatment. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study part of the European Network for the Investigation of Gender Incongruence (ENIGI), conducted between 15 February 2010 and 30 September 2015. There were 162 TW were included in the ENIGI study at the Ghent University Hospital in Belgium. Participants are included in ENIGI when they first start HT, and follow-up visits occur over the next 3 years. PARTICIPANTS/MATERIALS, SETTING METHODS: The study included 97 TW who initiated HT with cyproterone acetate (CPA) plus oestrogens and proceeded with gonadectomy at the Ghent University Hospital. Testicular tissue retrieved during gonadectomy was processed and stained for four different germ cell markers by the Biology of the Testis lab at the Vrije Universiteit Brussel. Subsequent immunohistochemical staining was performed for melanoma-associated antigen A4 (MAGE-A4, marker for spermatogonia and early spermatocytes), boule homologue, RNA-binding protein (BOLL, marker for secondary spermatocytes and round spermatids), cAMP-responsive element modulator (CREM, marker for round spermatids) and acrosin (marker for acrosome visualization). Serum levels of sex steroids were measured prior to surgery. MAIN RESULTS AND THE ROLE OF CHANCE: Suppressed testosterone levels (<50 ng/dl) were found in 92% of the participants prior to surgery. The mean time between initiation of HT and surgery was 685 days. In 88% (85/97) of the sections, MAGE-A4 staining was positive. Further staining could not reveal complete spermatogenesis in any participant. LIMITATIONS, REASONS FOR CAUTION: Testicular function of the participants prior to initiation of HT was not assessed, although all participants presented with cisgender male serum testosterone values before initiation of HT. The current study only reports on people using CPA at a fixed dose and may therefore not be applicable to all TW. WIDER IMPLICATIONS OF THE FINDINGS: HT leads to complete suppression of spermatogenesis in most TW, if serum testosterone levels within female reference ranges are obtained. Serum testosterone levels are associated with the sperm maturation rate. It is important to discuss sperm preservation before the start of hormone therapy. If serum testosterone levels remain higher, spermatogenesis may still occur. STUDY FUNDING/COMPETING INTEREST(S): D.V.S. is a post-doctoral fellow of the Fonds Wetenschappelijk Onderzoek (FWO; 12M2819N). Processing of the testis specimens was funded by the Biology of The Testes (BITE) research group (Department of Reproduction, Genetics and Regenerative medicine at Vrije Universiteit Brussel (VUB)). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Effects of testosterone therapy on constructs related to aggression in transgender men: A systematic review.

BACKGROUND: Transgender men are assigned female sex at birth, but identify as men. The anabolic and androgenic sex hormone testosterone has been positively associated with aggression. Therefore, transgender men are warned of increasing aggression when initiating testosterone therapy. AIM: To explore the literature regarding the effects of testosterone therapy on aggression-related constructs in transgender men. METHODS: Following PRISMA-guidelines, PsycINFO, MEDLINE®, EMBASE, and PubMed® were searched in November 2019. Risk of bias was analyzed using the Newcastle-Ottawa-Scale, and result-synthesis was grouped by aggression-outcome. RESULTS: Seven prospective cohort studies investigating aggression-dimensions pre- and post-testosterone therapy, reporting on data from 664 transgender men, were eligible. The studies had moderate to high risk of bias due to non-randomization, lack of appropriate control groups, and reliance on self-report. The behavioral tendency to react aggressively increased in three studies out of four (at three months follow-up), whereas only one study out of five found angry emotions to increase (at seven months follow-up). In contrast, one out of three studies reported a decrease in hostility after initiation of testosterone therapy. The remaining studies found no change in aggressive behavior, anger or hostility during hormone therapy. DISCUSSION AND CONCLUSION: Four out of seven studies reported an increase in aggression-related constructs, while one study reported a decrease. In all studies reporting changes, the follow-up period was less than 12 months, indicating that gender-affirming testosterone therapy could have a short-term impact on aggression-related constructs. However, the available studies carried a risk of bias, which indicates a need for further research.

Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI).

BACKGROUND: Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AIM: To evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. METHODS: In a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. MAIN OUTCOME MEASURE: Changes in CV risk factors and 30-year Framingham CVD risk during GAHT. CLINICAL IMPLICATIONS: In transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. STRENGTHS & LIMITATIONS: The strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. RESULTS: In transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes - such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. CONCLUSIONS: Our findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk. Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;18:821-829.

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group.

BACKGROUND: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. AIM: To examine the neurobiology of transgender persons in a large sample. METHODS: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. OUTCOMES: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. CLINICAL TRANSLATION: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. STRENGTHS AND LIMITATIONS: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

The effects of age and obesity on postprandial dynamics of serum testosterone levels in men.

OBJECTIVE: Guidelines recommend using fasting samples to evaluate testosterone (T) levels in men, as free and total T levels decrease postprandially. However, it is not clear whether these dynamics are affected by age or obesity. This could be relevant given the obesity epidemic, ageing population and the barrier for screening which fasting could impose. DESIGN/PARTICIPANTS: A total of 43 men underwent a solid mixed meal tolerance test. Serum samples were taken fasting, and at 30, 60 and 120 minutes postprandially. A commercial immunoassay was used to determine sex hormone-binding globulin (SHBG) levels, liquid chromatography coupled to tandem mass spectroscopy for total T concentrations and free T levels were calculated. RESULTS: Postprandially, both total and free T were lower at all-time points compared with fasting (all, P < .005). At 60 minutes, maximum mean decreases of 15 ± 15% and 17 ± 16% were seen for total and free T levels, respectively. Younger men had greater decreases in both total and free T levels compared with men older than 40 years (all, P < .05). A greater decrease at 30 and 60 minutes postprandially was observed for both total and free T levels in nonobese vs obese men (all, P < .05). CONCLUSIONS: After a mixed meal, total and free T serum levels decreased whereas SHBG levels did not change. Interestingly, postprandial decreases were less pronounced in men older than 40 years and/or with obesity. Although this study indicates less pronounced decreases in certain men, fasting samples remain a prerequisite for establishing correct diagnosis of male hypogonadism.

Neural and Hormonal Correlates of Sexual Arousal in Transgender Persons.

BACKGROUND: Whereas mounting work has begun to document the neural correlates underlying sexual arousal (SA) in humans, the associations between gender identity and the brain correlates of SA as well as their hormonal contributions remain unknown. AIM: This study investigated neural activation to sexual arousal in transgender and cisgender persons. METHODS: 20 transgender men and 19 transgender women (TW) already living in their identified gender were compared to 21 cisgender men (CM) and 19 cisgender women. Participants viewed erotic and neutral video clips while undergoing 3 Tesla magnetic resonance imaging. OUTCOMES: Group-specific brain activation, brain functional connectivity, and brain-hormone associations within the neurophenomenological model of sexual arousal (Stoleru et al, 2012). RESULTS: Consistent with the model, participants activated most of its components. However, between-group differences were mostly showing larger activation for CM relative to any of the other 3 groups. Moreover, functional connectivity analyses (psychophysiological interactions) indicated unique patterns for CM, cisgender women, and TW in how different components of SA communicated with one another. Finally, androgens in transgender men and estrogens in TW correlated negatively with parietal cortex and primary (sensori-) motor regions, respectively, while CM showed positive correlations of androgens with parietal cortex, somatosensory regions, and the insula. CLINICAL IMPLICATIONS: Data provide information on neurobiological changes in sexual arousal during treatment with gender-affirming hormone therapy. STRENGTHS & LIMITATIONS: Although a limitation is the lack of pretreatment data, the present study provides comprehensive information including brain activation, functional connectivity, and hormonal associations in a large sample. CONCLUSIONS: The results highlight a complex picture of the neural correlates of SA in gender identity and sex assigned at birth. Mueller SC, Wierckx K, T'Sjoen G. Neural and Hormonal Correlates of Sexual Arousal in Transgender Persons. J Sex Med 2020;17:2495-2507.

European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction".

BACKGROUND: There is a general lack of recommendations for and basic information tailored at sexologists and other health-care professionals for when they encounter trans people in their practice. AIM: We present to clinicians an up-to-date overview of clinical consensus statements on trans health care with attention for sexual function and satisfaction. METHODS: The task force consisted of 7 clinicians experienced in trans health care, selected among European Society for Sexual Medicine (ESSM) scientific committee. The consensus was guided by clinical experience and a review of the available literature and by interactive discussions on trans health, with attention for sexual function and satisfaction where available. OUTCOMES: The foci of the study are assessment and hormonal aspects of trans health care. RESULTS: As the available literature for direct recommendations was limited, most of the literature was used as background or indirect evidence. Clinical consensus statements were developed based on clinical experiences and the available literature. With the multiple barriers to care that many trans people experience, basic care principles still need to be stressed. We recommend that health-care professionals (HCPs) working with trans people recognize the diversity of genders, including male, female, and nonbinary individuals. In addition, HCPs assessing gender diverse children and adolescents should take a developmental approach that acknowledges the difference between prepubescent gender diverse children and pubescent gender diverse adolescents and trans adults. Furthermore, trans people seeking gender-affirming medical interventions should be assessed by HCPs with expertise in trans health care and gender-affirming psychological practice. If masculinization is desired, testosterone therapy with monitoring of serum sex steroid levels and signs of virilization is recommended. Similarly, if feminization is desired, we recommend estrogens and/or antiandrogen therapy with monitoring of serum sex steroid levels and signs of feminization. HCPs should be aware of the influence of hormonal therapy on sexual functioning and satisfaction. We recommend HCPs be aware of potential sexual problems during all surgical phases of treatment. CLINICAL IMPLICATIONS: This is an up-to-date ESSM position statement. STRENGTHS & LIMITATIONS: These statements are based on the data that are currently available; however, it is vital to recognize that this is a rapidly changing field and that the literature, particularly in the field of sexual functioning and satisfaction, is limited. CONCLUSION: This ESSM position statement provides relevant information and references to existing clinical guidelines with the aim of informing relevant HCPs on best practices when working with transgender people. T'Sjoen G, Arcelus J, De Vries ALC, et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med 2020;17:570-584.

Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence.

INTRODUCTION: Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender-affirming care. AIM: To prospectively assess sexual desire during the first 3 years of hormonal therapy (HT) in transgender people. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. At baseline, different psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. MAIN OUTCOME MEASURE: Prospective analysis of total, dyadic (with another person), and solitary (with oneself) sexual desire in 766 participants (401 transgender women [TW], 364 transgender men [TM]) was carried out using the Sexual Desire Inventory (SDI) questionnaire during a 3-year follow-up period, starting at the initiation of HT. Other factors associated with prospective changes were assessed. RESULTS: In TW, total, dyadic, and solitary SDI scores decreased during the first 3 months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable with baseline scores. In TM, total, dyadic, and solitary SDI scores increased over the first 3 months, remaining stable thereafter. However, total and dyadic SDI scores after 36 months were comparable with baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing menstrual bleeding or higher gender dysphoria levels at baseline (in TM only). CLINICAL IMPLICATIONS: This study offers clear data on the time course of sexual desire after starting HT and thereby helps to inform people who want to start HT. Transgender people can be informed that changes in sexual desire after initiating HT are temporary. Over a longer period of time, the current research does not suggest induction of hypoactive sexual disorder in TW or long-term increased sexual desire in TM. STRENGTH & LIMITATIONS: Strengths include the prospective design of this large multicentric study, the well-defined cohort, controlling for HT, sex steroids, and other factors. Limitations include performing a data lock, the absence of an objective measure of sexual desire, and the timing of laboratory measurements. CONCLUSION: Gender-affirming HT only induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT and sexual desire scores comparable with baseline in TM receiving virilizing HT, were observed. Defreyne J, Elaut E, Kreukels B, et al. Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence Study. J Sex Med 2020;17:812-825.

Effects of Gender-Affirming Hormones on Lipid, Metabolic, and Cardiac Surrogate Blood Markers in Transgender Persons.

BACKGROUND: Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised. CONTENT: A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles. SUMMARY: Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.

Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study.

OBJECTIVES: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD. DESIGN: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906). PATIENTS: Patients with mean urinary free cortisol (mUFC) ≤ upper limit of normal (ULN) or receiving clinical benefit at core study end could continue long-acting pasireotide during the extension. RESULTS: Eighty-one of 150 (54.0%) enrolled patients entered the extension. Median overall exposure to pasireotide at study end was 23.9 months; 39/81 (48.1%) patients completed the extension (received ≥ 12 months' treatment during the extension and could transit to a separate pasireotide safety study). mUFC was ≤ULN in 42/81 (51.9%), 13/81 (16.0%) and 43/81 (53.1%) patients at extension baseline, month (M) 36 and last assessment. Median mUFC remained within normal limits. Median late-night salivary cortisol was 2.6 × ULN at core baseline and 1.3 × ULN at M36. Clinical improvements were sustained over time. Forty-two (51.9%) patients discontinued during the extension: 25 (30.9%) before M24 and 17 (21.0%) after M24. Hyperglycaemia-related AEs occurred in 39.5% of patients. Mean fasting glucose (FPG) and glycated haemoglobin (HbA1c ) were stable during the extension, with antidiabetic medication initiated/escalated in some patients. Sixty-six (81.5%) and 71 (88.9%) patients were classified as having diabetes (HbA1c  ≥ 6.5%, FPG ≥ 7.0 mmol/L, antidiabetic medication use, or history of diabetes) at extension baseline and last assessment. CONCLUSIONS: Long-acting pasireotide provided sustained biochemical and clinical improvements, with no new safety signals emerging, supporting its use as an effective long-term therapy for CD.

No correlation between serum testosterone levels and state-level anger intensity in transgender people: Results from the European Network for the Investigation of Gender Incongruence.

INTRODUCTION: Anger is a state of emotions ranging from irritation to intense rage. Aggression implies externalizing anger through destructive/punitive behaviour. The World Professional Association for Transgender Health (WPATH) Standards of Care, Edition 7 (SOC7) guidelines warn about aggression in transgender men (TM) on testosterone treatment. We aimed to assess whether anger intensity increases in TM and decreases in transgender women (TW) after initiation of gender affirming hormone therapy and to identify predictors for anger intensity in transgender people. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Anger intensity was prospectively assessed in 898 participants (440 TM, 468 TW) by STAXI-2 (State-Trait Anger Expression Inventory-2) State Anger (S-Anger) during a three-year follow-up period, starting at the initiation of hormone treatment. Data were analysed cross-sectionally and prospectively. RESULTS: There was no change in STAXI-2 S-Anger scores. At three, twelve and thirty-six months of gender affirming hormone therapy, STAXI-2 S-Anger scores were not correlated to serum testosterone levels, although there was a correlation with various psychological measures after three and twelve months. TM experiencing menstrual spotting after three months had higher STAXI-2 S-Anger scores compared to those without (median 26.5 [18.0-29.8] versus 15.0 [15.0-17.0], P = 0.020). Changes in STAXI-2 S-Anger scores were not correlated to changes in serum testosterone levels after three, twelve and thirty-six months in TM or TW. CONCLUSIONS: State-level anger intensity is associated with psychological and/or psychiatric vulnerability, but not exogenous testosterone therapy or serum testosterone levels in transgender people.

Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People-Results from the European Network for the Investigation of Gender Incongruence.

INTRODUCTION: Although many studies on the short- and long-term effects of hormonal treatment (HT) in trans people focus on objective changes such as body composition or bone density, few studies have evaluated self-reported effects of HT. AIM: To evaluate self-reported symptoms during the first year of HT in trans people. METHODS: This study is part of the European Network for the Investigation of Gender Incongruence, a multicenter prospective cohort study. For this study, 205 trans women and 193 trans men from the gender clinics of Amsterdam, Ghent, and Florence, who were >18 years of age and started hormonal treatment were included. Questionnaires, self-developed based on the Menopause Rating scale and clinical experiences, were completed, and changes in symptom scores were analyzed using linear mixed models. MAIN OUTCOME MEASURES: Self-reported psycho vegetative symptoms, as well as physical, cognitive, emotional, sexual and genital complaints, and pain were evaluated at baseline and after 3, 6, and 12 months of HT using a 4-point Likert scale (no, mild, moderate, or severe complaints). RESULTS: In trans men, with a median age of 23, transient increases were reported in night sweats, weight gain, and clitoral pain. Persistent increases were reported for hot flashes, balding, voice instability, acne, and increase in sexual desire, whereas emotional instability, fear, and menses decreased. For trans women, with a median age of 29, hot flashes, night sweats, fatigue, weight gain, changes in olfactory sense, brittle nails, emotional instability, mood swings, and breast tenderness increased persistently during 12 months of HT, whereas a decrease was observed for balding and sexual desire. Sleeping difficulties decreased temporarily. No changes were observed in palpitations, dizziness, abdominal complaints, anxiety, panic attacks, cognition, and pain, except for clitoral and breast pain. CLINICAL IMPLICATIONS: Knowledge on the occurrence of these self-reported, subjective effects and their course over time may help physicians informing trans people starting with and during HT. STRENGTHS & LIMITATIONS: This study was performed in a large cohort of trans people. The follow-up period was limited to 12 months. CONCLUSION: Changes in self-reported symptoms were mentioned in all investigated areas, except cognition. Most symptoms were as expected and even desired, whereas others may be considered unpleasant by some trans people. van Dijk D, Dekker MJHJ, Conemans EB, et al. Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People-Results from the European Network for the Investigation of Gender Incongruence. J Sex Med 2019;16:1297-1309.