Internalized transphobia predicts worse longitudinal trend of body uneasiness in transgender persons treated with gender affirming hormone therapy: a 1-year follow-up study.

BACKGROUND: Given the relationship between interiorized stigma and body image, it could be hypothesized that high levels of internalized transphobia (IT) might predict higher levels of body uneasiness in subjects with gender dysphoria (GD) and worse improvement of body image after gender affirming hormone therapy (GAHT). AIM: We sought to evaluate the relationship between IT and body uneasiness in subjects with GD and the role of IT in moderating the improvement of body image after GAHT. METHODS: In total, 200 individuals with GD performed the baseline assessment; 99 were re-evaluated 12 months after starting GAHT. At baseline participants were evaluated through a face-to-face interview and filled self-administered questionnaires to evaluate GD (Utrecht Gender Dysphoria Scale [UGDS]), IT attitudes (Attitudes Toward Transgendered Individuals [ATTI] Scale), body uneasiness (Body Uneasiness Test, part A [BUT-A]), and general psychopathology (Symptom Checklist 90-Revised [SCL 90-R]). The same questionnaires, except ATTI, were readministered at follow-ups. OUTCOMES: Outcomes were based on measures of the associations between IT and baseline characteristics of the sample, the longitudinal trends of GD, body uneasiness, and general psychopathology; and IT as a moderator of the longitudinal trend of body uneasiness. RESULTS: At baseline, IT correlated with lower level of education, higher GD, and more severe body uneasiness. Longitudinal analyses showed significant improvements in GD, body uneasiness, and general psychopathology during GAHT. Moderation analysis confirmed that participants with more transphobic attitudes showed less improvement after GAHT with regard to body uneasiness (bTime*ATTI = -.002, P = .040). The Johnson-Neyman technique revealed that no significant improvement in body uneasiness was found for participants with ATTI scores lower than 71.14. CLINICAL IMPLICATIONS: The presence of IT should be investigated in subjects with GD who require gender affirming treatments to provide specific interventions aimed at targeting this dimension. STRENGTHS AND LIMITATIONS: Strengths of this study include the mixed cross-sectional and longitudinal design and the dimensional evaluation of the investigated constructs. Limitations include the small sample size and the limited follow-up. Furthermore, the effects of gender affirming surgery were not evaluated. CONCLUSION: The association of IT with both baseline body uneasinessand the longitudinal course of this dimension highlighted the clinical significance of body uneasiness and the importance of making continuous efforts to improve education and information to fight societal stigmas.

Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey.

BACKGROUND: Transgender people are a vulnerable group with a higher incidence of mental health issues and, during the COVID-19 outbreak, they may have faced psychological, physical and social obstacles. AIM: To evaluate the impact of the pandemic and the access to health care services during the COVID-19 pandemic on the mental health of the transgender people living in Italy. METHODS: An anonymous web-based survey was conducted among transgender people living in Italy. OUTCOMES: The survey consisted of 41 questions (to address socio-demographic and COVID-19 related variables, general health problems and trans-related health issues) and three validated questionnaires (the Impact of Event Scale [IES], the Beck Depression Inventory [BDI-II] and the SF-12. RESULTS: In total 108 respondents were included in the analysis, of these 73.1% were transmen and 26.9% transwomen. The mean age was 34.3 ± 11.7 years with 88.9% undergoing gender affirming hormonal treatment (GAHT). Of these respondents 55.6% were not working during the COVID-19 pandemic, mainly because they lost their jobs due to the lockdown (30.5%) or because they were otherwise unemployed (25.0%). Only four subjects were quarantined at home because of a positive COVID-19 swab. The mean total IES score was 21.1 ± 14.9 with 24.1% of subjects scoring over the cut-off score of 26 thereby suggesting a moderate-to-severe impact of the pandemic event. Mean BDI score was 8.6 ± 8.4. SF-12 total mean score was 96.1 ± 11.9 with a Mental Component Summary (MCS) score of 42.8 ± 9.1. Access to endocrinological consultations for hormonal prescription via telemedicine services was associated with better IES total scores (P = .01). CLINICAL IMPLICATIONS: Our results highlight the impact of the pandemic on the mental health of this particular population and how telemedicine services may serve to mitigate negative psychological effects. STRENGTHS & LIMITATIONS: Internet-based surveys may select a group of people not necessary representative of the whole population. The self-reporting bias should also be considered. Those who responded to our survey were mainly from northern Italy were COVID-19 has had a greater impact. CONCLUSION: Vulnerable groups such as the transgender population should receive more consideration also during pandemic events and their access to health services especially for endocrine and mental health care should be improved. A nationwide plan for the extended use of telemedicine should be established with targeted intervention to reduce psychological distress. Gava G, Fisher AD, Alvisi S, et al. Mental Health and Endocrine Telemedicine Consultations in Transgender Subjects During the COVID-19 Outbreak in Italy: A Cross-Sectional Web-Based Survey. J Sex Med 2021;18:900-907.

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.

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.

Brain Sex Differences Related to Gender Identity Development: Genes or Hormones?

The complex process of sexual differentiation is known to be influenced by biological and environmental determinants. The present review has the aim of summarizing the most relevant studies on the biological basis of sexual development, and in particular, it focuses on the impact of sex hormones and genetic background on the development of sexual differentiation and gender identity. The authors conducted a search of published studies on Medline (from January 1948 to December 2019). The evidence suggests that the sexual dimorphic brain could be the anatomical substrate of psychosexual development, on which gonadal hormones may have a shaping role during prenatal and pubertal periods. Additionally, according to several heritability studies, genetic components may have a role, but a promising candidate gene has not been identified. Even though growing evidence underlines the primary role of biological factors on psychosexual development, further studies are necessary to better explain their complex interactions.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

INTRODUCTION: An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. AIM: To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. METHODS: A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. MAIN OUTCOME MEASURES: Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). RESULTS: Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). CONCLUSION: The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality.

Conflicts Within the Family and Within the Couple as Contextual Factors in the Determinism of Male Sexual Dysfunction.

INTRODUCTION: The deterioration of a couple's relationship has been previously associated with impairment in male sexual function. Besides a couple's dystonic relationship, other stressors can unfavorably influence dyadic intimacy. A largely neglected etiopathogenetic factor affecting couple sexuality is the frustration caused by conflicts within the family. AIM: To evaluate the possible associations between male sexual dysfunction (SD) and conflictual relationships within the couple or the family. METHODS: A consecutive series of 3,975 men, attending the Outpatient Clinic for SD for the first time, was retrospectively studied. Conflicts within the family and within the couple were assessed using two standard questions: "Are there any conflicts at home," and "Do you have a difficult relationship with your partner?" respectively, rating 0 = normal relationships, 1 = occasional quarrels, and 2 = frequent quarrels or always. MAIN OUTCOME MEASURES: Several clinical, biochemical, and psychological (Middlesex Hospital Questionnaire) parameters were studied. RESULTS: Among the 3,975 patients studied, we observed a high prevalence of conflicts within the family and within the couple (32% vs. 21.2%). When compared with the rest of the sample, subjects reporting both type of conflicts showed a higher prevalence of psychiatric comorbidities. Hence, all data were adjusted for this parameter and for age. Family and couple conflicts were significantly associated with free floating anxiety, depression symptoms, and with a higher risk of subjective (self-reported) and objective (peak systolic velocity at the penile color Doppler ultrasound <35 mm/sec2) erectile dysfunction and hypoactive sexual desire. Female sexual function parameters, as reported by the patient, retained a significant association with both type of conflicts. CONCLUSIONS: This study indicates that the presence of often unexplored issues, like conflicts within the family or within the couple, can represent an important contextual factor in the determinism of male SD.

Lack of sexual privacy affects psychological and marital domains of male sexual dysfunction.

INTRODUCTION: Sexual dysfunctions (SDs) are dictated by predisposing, precipitating, maintaining, and contextual factors, the latter of which can help sexual problems to emerge. Even if the lack of sexual privacy is one of the most common contextual issues, it has not been extensively studied. AIM: Investigation of sexual privacy in a large sample of men consulting for SD was the aim of this study. METHODS: A consecutive series of 3,736 men, attending the outpatient clinic for SD for the first time, was retrospectively studied. Privacy during sexual intercourse was investigated with the following question, "During the last three months, have you had enough privacy during your sexual activity?" and rated 0 = yes, 1 = sometimes, 2 = rarely, and 3 = never. MAIN OUTCOME MEASURES: Several clinical, biochemical, and psychological (Middlesex Hospital Questionnaire [MHQ]) parameters were studied. RESULTS: Among the 3,736 patients studied, 83.9% reported enough privacy during sexual intercourse, while 8.6%, 5.7%, and 1.7% declared a decrease of sexual privacy of increasing severity. Lack of sexual privacy was associated with ejaculatory dysfunctions and with the inability to maintain an erection during intercourse. Subjects reporting lack of sexual privacy had a higher risk of relational and intrapsychic impairments, as well as psychopathology at MHQ questionnaire, even after adjusting for confounders. Fatherhood was associated with sexual privacy issues only in the lowest quartiles. In subjects without children, the absence of cohabitation with the partner was associated with an increasing risk of not having enough privacy (hazard ratio [HR] = 1.837 [1.269-2.659], P = 0.001); data confirmed, after stratification for age, only in the youngest subjects (I quartile HR = 2.159 [1.211-3.848], P = 0.009). CONCLUSIONS: This study indicates that sexual privacy is often a poorly investigated item, which is important to evaluate in male SD.

Facilitators and barriers in HIV testing and continuum of care among migrant transgender women who are sex workers residing in Florence, Italy.

Background: An increased risk of contracting HIV infection, suboptimal adherence, and a loss to follow-up have been observed in migrants, particularly if those individuals are transgender or sex workers. A clear picture of the HIV epidemic among migrants is complex due to the lack of specific national data. Aims: We developed a qualitative study that describes the barriers and facilitators (cultural, social, and personal) in HIV testing and the continuum of care for a group of migrant transgender women who are sex workers. Methods: A semi-structured interview was conducted with a group of migrant transgender women who are sex workers living with HIV or with unknown HIV serostatus residing in the Florentine metropolitan area. Results: We included 12 participants: 3 had unknown HIV serostatus and 9 were living with HIV in follow-up at the Clinic of Infectious and Tropical Diseases, Careggi University hospiral, Florence, Italy. Among barriers, the perceived stigma due to their identity as migrants and transgender people, the language lack of ability and the legal position in the host country played a significant role. Moreover, the interviewees claimed having no alternative to sex work: for those individuals, changing their lifestyle condition is perceived as difficult or impossible due to social prejudices. Conversely, the interviewees considered support services, such as cultural mediators/interpreters and street units, as facilitators to HIV testing, access to care, and continuum of care. Having regular and accessible ART and the availability of a more consistent health care system, represent reasons for HIV-positive migrants living with HIV to move to Italy. Conclusions: Knowledge of this population's personal experience regarding the barriers and factors that facilitate access to the HIV care system is essential for planning public health interventions capable of responding to the real needs of patients.

Gender identity disorder and eating disorders: similarities and differences in terms of body uneasiness.

INTRODUCTION: Subjects with gender identity disorder (GID) have been reported to be highly dissatisfied with their body, and it has been suggested that the body is their primary source of suffering. AIMS.: To evaluate quality and intensity of body uneasiness in GID subjects, comparing them with a sample of eating disorder patients and a control group. To detect similarities and differences between subgroups of GID subjects, on the basis of genotypic sex and transitional stage. METHODS: Fifty male-to-female (MtF) GID (25 without and 25 with genital reassignment surgery performed), 50 female-to-male (FtM) GID (28 without and 22 with genital reassignment surgery performed), 88 eating disorder subjects (26 anorexia nervosa, 26 bulimia nervosa, and 36 binge eating disorder), and 107 healthy subjects were evaluated. MAIN OUTCOME MEASURES: Subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Symptom Checklist (SCL-90), and the Body Uneasiness Test (BUT). RESULTS: GID and controls reported lower psychiatric comorbidity and lower SCL-90 General Severity Index (GSI) scores than eating disorder subjects. GID MtF without genital reassignment surgery showed the highest BUT values, whereas GID FtM without genital reassignment surgery and eating disorder subjects showed higher values compared with both GID MtF and FtM who underwent genital reassignment surgery and controls. Considering BUT subscales, a different pattern of body uneasiness was observed in GID and eating disorder subjects. GID MtF and FtM without genital reassignment surgery showed the highest BUT GSI/SCL-90 GSI ratio compared with all the eating disorder groups. CONCLUSIONS: GID and eating disorders are characterized by a severe body uneasiness, which represents the core of distress in both conditions. Different dimensions of body uneasiness seem to be involved in GID subsamples, depending on reassignment stage and genotypic sex. In eating disorder subjects body uneasiness is primarily linked to general psychopathology, whereas in GID such a relationship is lacking.

"It takes two to tango": the relational domain in a cohort of subjects with erectile dysfunction (ED).

INTRODUCTION: The relational domain of erectile dysfunction (ED) is difficult to investigate in a clinical setting. We developed and validated SIEDY, a 13-item structured interview, that evaluates, besides the organic (Scale 1) and intra-psychic (Scale 3) domains, also the relational one (Scale 2). We previously established a pathological threshold for SIEDY Scale 1 and 3. AIM: The aim of this study is to identify a pathological threshold of SIEDY Scale 2. METHOD: A nonselected, consecutive series of 2,992 subjects with ED was retrospectively evaluated. In a first consecutive series of 844 patients (Sample A, studied without systematically applying a psychometric test: Middlesex Hospital Questionnaire), a pathological threshold of SIEDY Scale 2 score was identified through receiver operating characteristic, using, as surrogate marker of impaired couple relationship, at least a positive answer to two standard questions on conflict within the couple and on the presence of extramarital affairs. MAIN OUTCOME MEASURE: Sensitivity and specificity, along with possible associations with biological and psychological correlates were verified in a further sample of 2,148 patients (Sample B). RESULTS: In Sample A, a threshold of Scale 2 score ≥2 predicts couple impairment with a sensitivity of 53% and specificity of 66% and an overall accuracy of 62.0 ± 2.2% (P < 0.0001). When this threshold was verified in sample B, Scale 2 score ≥2 was associated with a higher risk of anxiety and depressive symptoms, higher prevalence of psychopathology, and higher Scale 3 scoring, even after adjusting for confounders. In the same sample, a Scale 2 score ≥2 was associated with a reduced intimacy during sexual intercourse and overall worse sexual functioning. CONCLUSIONS: Until now, no instrument is available to quantify the marital domain of ED. The validation of a threshold of SIEDY Scale 2 score (≥2) represents an easy tool for the identification of ED patients with a relevant marital impairment.

The ENIGI (European Network for the Investigation of Gender Incongruence) Study: Overview of Acquired Endocrine Knowledge and Future Perspectives.

Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on mortality rates, oncological risk, and cardiovascular, cerebrovascular and thromboembolic events are lacking. With this aim, we decided to extend the observation of the ENIGI study to 10 years in order to study all these aspects in depth and to answer these questions.

A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development.

INTRODUCTION: Deficiency of the 17ß-hydroxysteroid dehydrogenase type 3 (17 ß-HSD3) is a rare autosomal recessive 46,XY Difference of sex development (DSD), resulting from pathogenetic variants in the HSD17B3 gene, which lead to absent or reduced ability to convert Δ4-androstenedione to testosterone in the fetal testes. AIM: This study aimed to present the clinical and genetic characteristics of an Italian patient receiving a diagnosis of 17 ß-HSD3 deficiency in adulthood. The patient was raised as female and underwent early surgical interventions to correct virilized genitalia, leading to a significant sexual distress. METHODS: At the time of the referral, a 20-gene Next Generation Sequencing custom-panel for DSD was performed on patient's genomic DNA. RESULTS: A novel compound heterozygous mutation in HSD17B3 gene was identified, detecting a new variant (c.257_265delAGGCCATTG, p.) CONCLUSION: Novel genotype causing 17 ß-HSD3 deficiency is presented. Furthermore, the patient's clinical history stresses the importance to actively involve these individuals in the decision-making process avoiding surgical intervention when the patient is not able to give fully informed consent. Cocchetti C, Baldinotti F, Romani A, et al. A Novel Compound Heterozygous Mutation of HSD17B3 Gene Identified in a Patient With 46,XY Difference of Sexual Development. Sex Med 2022;10:100522.

The fMRI correlates of visuo-spatial abilities: sex differences and gender dysphoria.

The contribution of brain regions to visuospatial abilities according to sex differences and gender identity is inconsistently described. One potential explaining factor may be the different tasks employed requiring a variable load of working memory and other cognitive resources. Here we asked to 20 cis and 20 transgender participants to undergo functional Magnetic Resonance Imaging during performance of a judgement line of orientation test that was adapted to explore the basic visuospatial processing while minimizing the working memory load. We show that V1 activation may be viewed as a brain area with enhanced activation in males, regardless of participants' gender identity. On its turn, gender identity exclusively influences the visuospatial processing of extrastriate visual areas (V5) in women with gender dysphoria. They showed enhanced V5 activation and an increased functional connectivity between V5 and V1. Overall our neuroimaging results suggest that the basic visuospatial abilities are associated with different activations pattern of cortical visual areas depending on the sex assigned at birth and gender identity.

Prevalence and Correlates of Sexually Transmitted Infections in Transgender People: An Italian Multicentric Cross-Sectional Study.

The burden of sexually transmitted infections (STIs) in the transgender population remains an underestimated issue. The aims of the present study were to evaluate the prevalence of either self-reported and serological STIs and to describe socio-demographic and clinical characteristics of transgender individuals with STIs. A consecutive series of 705 transgender individuals (assigned-male at birth, AMAB n = 377; assigned-female at birth, AFAB n = 328) referring to six Italian gender clinics were included. Sociodemographic and clinical information was collected during the first visit. In a subsample of 126 individuals prevalence of STIs (human immunodeficiency virus, HIV; hepatitis C, HCV; hepatitis B, HBV; syphilis) were evaluated through serology tests. The self-reported prevalence of HIV, HBV, HCV and syphilis infection in the total sample were 3.4%, 1.6%, 2.6% and 2.0%, respectively. In the subsample who underwent serological tests, higher rates of serological prevalence were found (9.5%, 4.0%, 5.6% and 7.9% for HIV, HBV, HCV and syphilis, respectively). When comparing transgender people with or without self-reported STIs, unemployment, previous incarceration, justice problems and sex work resulted more frequent in the first group (p< 0.03 for all). Regarding health status, we observed higher rates of lifetime substance abuse and psychiatric morbidities in trans people with at least one reported STI (p < 0.05). The prevalence of STIs exceeded that reported in general population and STIs correlates underline the importance of stigma and discrimination as determinants of transgender health.

Positive and Negative Affect Changes during Gender-Affirming Hormonal Treatment: Results from the European Network for the Investigation of Gender Incongruence (ENIGI).

Improving transgender people's quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In the European Network for the Investigation of Gender Incongruence (ENIGI) study, we prospectively collected data of 873 participants (451 transwomen (TW) and 422 transmen (TM)). At baseline, psychological questionnaires including the Positive and Negative Affect Schedule (PANAS) were administered. The PANAS, levels of sex steroids and physical changes were registered at each follow-up visit during a 3-year follow-up period, starting at the initiation of hormonal therapy. Data were analyzed cross-sectionally and prospectively. Over the first three months, we observed a decline in positive affect (PA) in both TM and TW. Thereafter, PA reached a steady state in TW, whereas in TM there was also a second decline at 18 months. In both TM and TW there was no persisting difference comparing baseline to the 36-months results. Concerning negative affect (NA), we observed a decline during the first year in TM, which sustained during the second year and was not different anymore at 36 months compared to baseline. In TW though, we did not find any change of NA during the entire follow-up. Even if some of these results show significant differences, they should be considered with caution, since there was no control group and the absolute differences are small. No association between affect and the level of sex steroids was observed. Baseline QoL and psychological burden are related to affect independently from gender but are not necessarily good predictors of the evolution of one's affect during the gender-affirming process. Further research is necessary to investigate these preliminary results.

Priapus is happier with Venus than with Bacchus.

INTRODUCTION: The relationship between alcohol consumption and erectile function is still not completely clarified. AIM: Aims of the present study are to explore a number of biological and clinical correlates of alcohol consumption in a sample of men consulting for sexual dysfunction, and to verify possible associations with the incidence of major adverse cardiovascular events (MACEs). METHODS: A consecutive series of 1956 (mean age 55 ± 11.9 years old) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N = 1687) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES: Different clinical, biochemical, instrumental (penile Doppler ultrasound [PCDU]), and intrapsychic (Middlesex Hospital Questionnaire [MHQ]) were evaluated. We considered alcohol abuse more than three drinks per day. RESULTS: Among the patients studied 81% reported no or mild (<4 drinks/day) alcohol consumption whereas 14.3% and 3.9% declared a moderate (4-6 drinks/day) or severe (>6 drinks/day) alcohol abuse, respectively. After adjustment for confounders, both moderate or severe alcohol abuse was associated with low perceived partner's sexual desire, worse couple relationship, and smoking abuse. Furthermore, moderate and severe alcohol abuse was associated with low prolactin and thyroid-stimulating hormone levels, as well as an increase in triglycerides and total cholesterol levels. Penile blood flow was reduced in moderate and severe alcohol drinkers even after adjustment for confounders. In the longitudinal study, after adjusting for confounding factors, any kind of alcohol abuse was independently associated with a higher incidence of MACE (hazard ratio = 2.043 [1.059-3.943]; P < 0.0001). CONCLUSIONS: Our findings demonstrate that, in subjects consulting for erectile dysfunction, severe alcohol consumption is associated with a worse sexual function and a higher incidence of MACE.

Management of hypoactive sexual desire disorder in transgender women: a guide for clinicians.

Hypoactive sexual desire disorder (HSDD) represents a common condition among transgender women. However, to date no specific guidelines for the management of HSDD in transgender persons are available. The aim of the present narrative Review is to evaluate evidence-based treatment for HSDD and to suggest treatment options for HSDD in transgender women. Clinically relevant publications on the management of HSDD (from 1985 to 2020) were searched in PubMed and Medline databases, using the following terms: "sexual desire", "sexual health", "HSDD", "transgender", "gender-affirming treatment", "sexual therapy", "testosterone treatment", "Central nervous system-active medications", and variants. Since sexual desire could be affected by several factors, a comprehensive assessment of HSDD- exploring biological, psychological, and social domains- is recommended, in order to identify possible predisposing, precipitating and maintaining factors. Among treatment options, transgender women may benefit of different sex therapy strategies and/or central nervous system-active medications-such as flibanserin, bremelanotide, bupropion and buspirone-and transdermal testosterone, bearing in mind that this option could be poorly accepted by patients due to the risk of virilizing effects. The lack of data regarding the efficacy of HSDD treatment options in transgender women emphasize the need for literature to focus more on this topic in the future.