A European Network for the Investigation of Gender Incongruence in adolescents.

BACKGROUND: Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment. AIM: We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data. METHODS: The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence. OUTCOMES: Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT. RESULTS: Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing. CLINICAL IMPLICATIONS: In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions. STRENGTHS AND LIMITATIONS: This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included. CONCLUSION: With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents.

Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Exploring Gender Diversity in Transgender and Non-Binary Adults Accessing a Specialized Service in Italy.

In Italy, studies investigating gender identity and expression in gender non-conforming adults are lacking, as well as data regarding the non-binary population. The present study aimed at dimensionally exploring how transgender and non-binary Italian adults identify and express their gender. The Gender Diversity Questionnaire (GDQ) was administered to a sample of 112 adult subjects aged 18-60 years accessing a gender-specialized service in Rome. The majority of the participants were aged 18-24 years (53.6%), whereas fewer subjects were aged 25-35 years (32%) and 35 years and older (14.3%). Most participants (83.9%) identified themselves as trans binary, while the remaining (16.1%) identified as non-binary. Trans binary participants reported a stable gender identity, whereas non-binary participants reported a more fluid gender identity over time and across contexts. Younger subjects recognized the use of chosen names, pronouns, and clothes as important for their gender expression, whereas older subjects attributed more importance to physical appearance and emotions. Differences regarding gender-affirmative interventions emerged between non-binary and transbinary participants. Findings evidence that gender non-conforming adults accessing gender-specialized services have unique needs and features, thus it is essential to shed light on this population by providing greater visibility and recognition.

Sex hormones, insomnia, and sleep quality: Subjective sleep in the first year of hormone use in transgender persons.

STUDY OBJECTIVES: Transgender persons can use gender-affirming hormone therapy (GAHT) to align their physical appearance with their identified gender. Many transgender persons report poor sleep, but the effects of GAHT on sleep are unknown. This study examined the effects of a 12 months of GAHT use on self-reported sleep quality and insomnia severity. METHODS: A sample of 262 transgender men (assigned female at birth, started masculinizing hormone use) and 183 transgender women (assigned male at birth, started feminizing hormone use), completed self-report questionnaires on insomnia (range 0-28), sleep quality (range 0-21) and sleep onset latency, total sleep time and sleep efficiency before start of GAHT and after 3, 6, 9, and 12 months of GAHT. RESULTS: Reported sleep quality showed no clinically significant changes after GAHT. Insomnia showed significant but small decreases after 3 and 9 months of GAHT in trans men (-1.11; 95%CI: -1.82; -0.40 and -0.97; 95%CI: -1.81; -0.13, respectively) but no changes in trans women. In trans men, reported sleep efficiency decreased by 2.8% (95%CI: -5.5%; -0.2%) after 12 months of GAHT. In trans women, reported sleep onset latency decreased by 9 min (95%CI: -15; -3) after 12 months of GAHT. CONCLUSIONS: These findings show that 12 months of GAHT use did not result in clinically significant changes in insomnia or sleep quality. Reported sleep onset latency and reported sleep efficiency showed small to modest changes after 12 months of GAHT. Further studies should focus on underlying mechanisms by which GAHT could affect sleep quality.

Gender Identity and Non-Binary Presentations in Adolescents Attending Two Specialized Services in Italy.

BACKGROUND: Recently, the variability and heterogeneity of gender presentations in transgender youths have gained significant attention worldwide. Alongside this, specialized gender services have reported an increase in referrals of youths reporting non-binary identities. In Italy, studies investigating gender identity and expression in gender non-conforming youths are lacking, as are data regarding the non-binary population. AIM: The present study aimed at dimensionally exploring how transgender and non-binary Italian adolescents identify and express their gender. OUTCOMES: Gender expression in trans binary youths and non-binary youths. METHODS: The Gender Diversity Questionnaire (GDQ; Twist & de Graaf, 2019) was used to investigate gender identity, gender fluidity, and gender expression in a sample of 125 adolescent patients from the Gender Identity Development Service (SAIFIP) in Rome and the Gender Incongruence Unit of the Careggi Hospital in Florence, between April 2019-June 2021. RESULTS: The majority of participants (74.4%) identified as trans* binary and the remaining (25.6%) participants identified as non-binary. Trans binary participants reported a stable gender identity, whereas non-binary participants reported a more fluid gender identity across time and contexts. Almost all participants rated external appearance as important to their gender expression, yet trans binary participants attributed more importance to the body in this respect. Body discomfort and pubertal stage emerged as the most influential factors in participants' experiences of gender. Participants who were assigned male at birth expressed significantly more desire for puberty blockers, whereas those who were assigned female at birth had a stronger desire to engage in breast/chest surgery. Non-binary participants sought different medical interventions relative to trans binary participants. CLINICAL IMPLICATIONS: These results may be useful for clinicians working with transgender youths as they provide awareness regarding the features of young people who identify within and outside of binary constructions of gender. STRENGTHS & LIMITATIONS: This study provides useful data in gaining insight into understanding the variety of experiences and challenges of gender non-conforming youths. However as the sample was recruited from specialized services, it may not represent the entire gender non-conforming population in Italy. CONCLUSION: The results describe the range of gender identities and expressions among gender non-conforming youths attending gender specialized services in Italy, thereby improving our understanding of the variety of identities experienced and the specific medical needs of both trans binary and non-binary adolescents. Mirabella M, Piras I, Fortunato A, et al. Gender Identity and Non-Binary Presentations in Adolescents Attending Two Specialized Services in Italy. J Sex Med 2022;19:1035-1048.

ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery".

INTRODUCTION: Much has been published on the surgical and functional results following Gender Affirming Surgery ('GAS') in trans individuals. Comprehensive results regarding sexual wellbeing following GAS, however, are generally lacking. AIM: To review the impact of various GAS on sexual wellbeing in treatment seeking trans individuals, and provide a comprehensive list of clinical recommendations regarding the various surgical options of GAS on behalf of the European Society for Sexual Medicine. METHODS: The Medline, Cochrane Library and Embase databases were reviewed on the results of sexual wellbeing after GAS. MAIN OUTCOMES MEASURE: The task force established consensus statements regarding the somatic and general requirements before GAS and of GAS: orchiectomy-only, vaginoplasty, breast augmentation, vocal feminization surgery, facial feminization surgery, mastectomy, removal of the female sexual organs, metaidoioplasty, and phalloplasty. Outcomes pertaining to sexual wellbeing- sexual satisfaction, sexual relationship, sexual response, sexual activity, enacted sexual script, sexuality, sexual function, genital function, quality of sex life and sexual pleasure- are provided for each statement separately. RESULTS: The present position paper provides clinicians with statements and recommendations for clinical practice, regarding GAS and their effects on sexual wellbeing in trans individuals. These data, are limited and may not be sufficient to make evidence-based recommendations for every surgical option. Findings regarding sexual wellbeing following GAS were mainly positive. There was no data on sexual wellbeing following orchiectomy-only, vocal feminization surgery, facial feminization surgery or the removal of the female sexual organs. The choice for GAS is dependent on patient preference, anatomy and health status, and the surgeon's skills. Trans individuals may benefit from studies focusing exclusively on the effects of GAS on sexual wellbeing. CONCLUSION: The available evidence suggests positive results regarding sexual wellbeing following GAS. We advise more studies that underline the evidence regarding sexual wellbeing following GAS. This position statement may aid both clinicians and patients in decision-making process regarding the choice for GAS. Özer M, Toulabi SP, Fisher AD, et al. ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery". Sex Med 2022;10:100471.

Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals.

BACKGROUND: Over the last few years, the gender binary has been questioned, highlighting the existence of gender diverse people, who identify as neither (exclusively) male nor female. AIM: The present study evaluated the possible differences in terms of psychological wellbeing between binary and gender diverse individuals, as well as the role of perceived social acceptance and religious fundamentalism as possible mediators of psychopathology in gender diverse people. Furthermore, the diversity of gender-affirming hormonal treatment requests according to gender identification was investigated. METHODS: A sample of 563 transgender people aged 18-70 was enrolled (n = 264 assigned female at birth, AFAB and n = 299 assigned male at birth, AMAB), all individuals referring to several Italian gender clinics. A subdivision of the study population based on the gender identity visual analog scale (GI-VAS) median was performed, in order to distinguish between gender diverse and binary transgender individuals. Moreover, a linear regression analysis was performed entering logarithmically transformed GI-VAS (Log GI-VAS) into the models with psychometric scales. OUTCOMES: Psychometric and sociodemographic data, as well as information regarding requests for gender-affirming treatments, were extrapolated from the clinical interviews conducted during the first referral. RESULTS: Gender diverse individuals showed significantly less intense gender dysphoria and higher levels of depression and anxiety compared to binary ones; accordingly, a less binary gender identity correlated with higher levels of depression and anxiety and lower levels of gender dysphoria. The depressive symptomatology in gender diverse people was partially mediated by perceived discrimination and humiliation. Moreover, gender diverse AMAB people sought a non-standard hormonal treatment more often than their binary counterpart. CLINICAL IMPLICATIONS: The present study highlights the importance for transgender health professionals, when planning gender-affirming hormonal treatments, to offer flexible interventions, tailored on the patient's needs and goals. STRENGTHS & LIMITATIONS: Strengths included exploring whether and how perceived discrimination may affect mental health in gender diverse people. Limitations included the enrolled sample of people referring to different gender clinics, which is not fully representative of the transgender population. CONCLUSION: This study highlights the importance of evaluating each individual's unique health care needs, exploring each single request and its underlying reasons. Romani A., Mazzoli F., Ristori J., et al. Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals. J Sex Med 2021;18:1933-1944.

Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study.

CONTEXT: Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. OBJECTIVE: To assess the lowest effective dose of CPA in trans women to prevent side effects. METHODS: This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy. RESULTS: Using estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the predefined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses. CONCLUSION: Compared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.

Vaginal bleeding and spotting in transgender men after initiation of testosterone therapy: A prospective cohort study (ENIGI).

BACKGROUND: Previous studies have cross-sectionally described amenorrhea in cohorts of transgender men on intramuscular or subcutaneous testosterone injections. It remains uncertain which testosterone preparations most effectively suppress vaginal bleeding and when amenorrhea occurs after testosterone initiation. AIM: To investigate the clinical effects of various testosterone preparations on vaginal bleeding and spotting in transgender men. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Data on the persistence and intensity of vaginal bleeding and spotting, serum sex steroid levels and body composition were prospectively and cross-sectionally assessed in 267 transgender men during a three-year follow-up period, starting at the initiation of various testosterone preparations. RESULTS: After three months of testosterone, 17.9% of transgender men reported persistent vaginal bleeding and 26.8% reported spotting. The percentages reporting vaginal bleeding and spotting decreased over the first year of testosterone (bleeding 4.7% and spotting 6.9% at 12 months, respectively), with no participants reporting vaginal bleeding or spotting after 18 months of testosterone. Factors associated with vaginal bleeding or spotting included lower serum testosterone levels and being on testosterone gel as compared to injections (e.g., esters or undecanoate preparations). If vaginal bleeding persisted, starting progestogens at three months resulted in a decrease in the intensity of vaginal bleeding and spotting. DISCUSSION: Transgender men and hormone-prescribing providers can be reassured that vaginal bleeding and spotting usually stop within three months after testosterone initiation. If not, serum testosterone levels should be measured and testosterone dose adjusted to achieve serum testosterone levels in the physiologic male range. Adding a progestin can be considered after three to six months if bleeding persists. Providers should be aware that cessation of bleeding can be more difficult to achieve in transgender men with lower serum testosterone levels or those on testosterone gel.

Predictors of Resumption of Menses in Anorexia Nervosa: A 4-Year Longitudinal Study.

OBJECTIVE: Amenorrhea is a disabling medical consequence of anorexia nervosa (AN); therefore, resumption of menses (ROM) represents an important goal in the treatment for these patients. The aim of the present study was to evaluate possible clinical, psychopathological, and biological predictors of ROM, including age, body mass index (BMI), AN subtype, childhood abuse, duration of illness, general and eating disorder (ED)-specific psychopathology, and sex hormones. METHODS: Fifty amenorrheic patients with AN were enrolled. Baseline clinical data and information on childhood abuse were collected. Questionnaires to evaluate general and ED-specific psychopathology were administered, and blood samples were drawn. All patients received treatment as usual and underwent regular follow-up visits for 4 years or until ROM. Time to ROM, BMI at last evaluation, and data regarding diagnostic crossover into bulimia nervosa were collected. RESULTS: Twenty-nine (58.0%) patients recovered menses. Diagnostic crossover was associated with a higher probability of ROM (odds ratio = 10.3, p = .030). Time-to-event analysis showed that a shorter duration of illness (χ(1) = 11.00, p = .001), binge-eating/purging subtype (χ(1) = 7.01, p = .008), and history of childhood abuse (χ(1) = 4.03, p = .045) were associated with an earlier ROM. Furthermore, higher baseline ED-specific psychopathology was associated with a reduced likelihood for ROM, whereas higher general psychopathology and follicle-stimulating hormone levels predicted an earlier ROM (all, p < .050). Age, BMI, luteinizing hormone, and estrogen hematic levels had no predictive value with respect to ROM. CONCLUSIONS: The present study provides data in support of an integrated model, emphasizing the importance of duration of illness, childhood abuse, and psychopathological characteristics of amenorrheic patients with AN in predicting ROM.

When Testosterone Needs to be Contrasted: A Preliminary Study of Scar Prevention in Transmen Top Surgery with an Innovative Galenic Preparation.

BACKGROUND: Transmen are individuals who live a marked incongruence between the assigned gender and the experienced gender. Crucial and life-changing steps in their transition are testosterone treatment and mastectomy to remove the stigma of feminine identity. After surgery, patients' attention turns to the scars, often not aesthetically pleasant. We thus created an innovative galenic preparation for scar treatment after surgery composed by spironolactone, alfa bisabolol and silicone gel. Functional outcomes, side effects and satisfaction were assessed. METHODS: For the present prospective randomized controlled study, 30 patients with similar demographic characteristics who underwent double incision mastectomy with NA grafts between February 2014 and June 2019 were selected. The treatment Group A (n = 15) was treated for 12 months with "Top Surgery Scar go," the control Group B (n = 15) with silicon gel. Statistical analysis including Wilcoxon test and Kruskal-Wallis test per variable was performed. To assess satisfaction, a second Wilcoxon test was applied. RESULTS: The differences between Group A and Group B were statistically significant, especially at T12 with very low p values. Satisfaction was greater in Group A (p value = 3e-4). No major side effects were noticed in Group A. CONCLUSIONS: TSSgo scar innovative treatment showed long-term efficacy in comparison with silicon gel in terms of improved scar tissue texture, pigmentation, pliability and height. It is easy to set up, cost-effective and safe. Further studies are necessary to better assess efficacy and validity of TSSgo, but it appears to be promising as the new treatment of reference for scar management after top surgery in transmen. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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.

Lower Serum Estradiol Levels in Assigned Female at Birth Transgender People with Initiation of Testosterone Therapy: Results from the European Network for the Investigation of Gender Incongruence.

Purpose: Concerns have been raised about undesired estrogenic effects in assigned female at birth (AFAB) transgender people on testosterone therapy. How serum estradiol levels change after initiation of testosterone therapy and if these levels should be monitored remain unclear. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. Serum levels of sex steroids were assessed in 746 AFAB transgender people during a 3-year follow-up period, starting at the initiation of hormone treatment. Results: Estradiol levels decreased from median [P25-P75] 45.6 [24.0-102.2] pg/mL to 36.5 [25.0-46.2] pg/mL over 3 years (p < 0.001); a change was already noticeable during the first 3 months (mean -17.1 pg/mL, 95% confidence interval -23.8 to -10.6, p < 0.001). Serum estradiol levels were lower in people without endogenous estradiol production from ovarian source (contraceptive users or post hystero-oophorectomy) at baseline and after 3 months, compared with people with endogenous estradiol production. Using long-acting testosterone undecanoate injections resulted in a more prominent decrease in serum estradiol values over 12 months, compared with short-acting mixed testosterone esters (p < 0.001) or testosterone gel (p = 0.001). Changes in serum estradiol were positively correlated to changes in luteinizing hormone (ρ = 0.107, p < 0.001) and negatively correlated to changes in follicle-stimulating hormone levels (ρ = -0.167, p < 0.001) and body mass index (ρ = -0.082, p < 0.001). Conclusion: Testosterone administration in AFAB transgender people resulted in decreasing serum estradiol levels. Our results suggest that testosterone therapy leads to central suppression of estradiol production, with partial restitution due to aromatization.

Sexual habits among Italian transgender adolescents: a cross-sectional study.

Recent studies showed that transgender (TGN) adolescents are more at risk of negative sexual outcomes than their peers. However, little is known about the psychopathological and sociodemographic correlates of sexual-related experiences in TGN adolescents. This cross-sectional study aimed at overcoming this limitation describing this association in a sample of 18 transgirls and 32 transboys recruited at the Gender Clinic of the University of Florence between 2015 and 2020. Clinical, sociodemographic, and sexual-related features were collected through a face-to-face interview and anamnestic forms. Self-report questionnaires were administered to evaluate gender dysphoria (Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults), emotional and behavioral problems (Youth Self Report), and body uneasiness (Body Uneasiness Test). The percentage of subjects reporting to have had at least one romantic relationship in life was 62.5% among transboys and 16.7% in transgirls (ORsex = 8.65, p < 0.01), whereas 28.1% of transboys and 5.6% of transgirls were sexually active (ORsex = 6.63, p > 0.05). A worse psychological functioning and risk-taking behaviors were associated with being sexually active (p < 0.05). These results underline the deep interconnection between psychological vulnerability and sexual-related features in TGN adolescents, confirming the importance of developing gender inclusive sex education programs to prevent negative sexual outcomes in this population.

Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data.

INTRODUCTION: As far as we know, no studies to date have investigated the psychobiological correlates of sexual distress (SD) nor the impact of hormonal treatment (HT) on SD in transgender persons. AIM: To evaluate the psychobiological correlates of SD and assess the effects of HT on SD in transgender persons without gender-affirming surgery. METHODS: A consecutive series of 301 transgender persons (160 transwomen and 141 transmen) was considered for the cross-sectional study, and a subset of 72 subjects was studied in a 2-year follow-up. A physical examination was performed. Blood samples were drawn for determination of cortisol levels. Subjects completed psychometric measures. During 2 years of HT, the evaluation of SD was prospectively repeated. MAIN OUTCOME MEASURE: Psychobiological correlates of SD in transgender population. Changes in SD during gender affirming hormonal treatment. CLINICAL IMPLICATIONS: Knowing how hormonal treatment influence SD will help care providers when counseling transgender people. STRENGTHS & LIMITATIONS: To the authors' knowledge, this is the first study prospectively evaluating the impact of gender affirming hormonal treatment on sexual distress in transgender individuals. The main limitations are represented by the small size of the sample and the use of questionnaires validated only in the cisgender population. RESULTS: SD showed a positive correlation with body uneasiness (P < .0001) and with dissatisfaction toward gender-related body parts or shapes (all P < .05). In addition, SD correlated positively with general psychopathology (P < .0001), alexithymia, social anxiety, and humiliation scales (all P < .05). In transmen, SD was positively associated with autism levels (P < .005), as well as with cortisol levels (P < .02). A significant correlation between SD and perceived discrimination was observed in transwomen (P < .05). In transwomen, SD was positively associated with hair density and negatively with breast growth (both P < .05). Finally, in transmen, a negative correlation was found between SD and hair density (P < .05). When the impact of HT on SD was evaluated, a significant reduction of SD was observed across time in both transwomen and transmen (P = .001 and P = .01, respectively). CONCLUSIONS: The present results support the efficacy of HT in reducing SD in transgender persons. Ristori J, Cocchetti C, Castellini G, et al. Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data. J Sex Med 2020;17:142-151.

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.

Gender Dysphoria and Anorexia Nervosa Symptoms in Two Adolescents.

The co-occurrence of gender dysphoria and anorexia nervosa has been described in the scientific literature. This paper presents two adolescents with gender dysphoria and pathological eating behaviors and questions with longitudinal observations the clinical meaning of anorexia nervosa symptoms (e.g., restricting eating behaviors and fear of gaining weight) in adolescents with gender dysphoria. Both received psychological evaluations at different times: at first admission to the gender dysphoria clinic (T0) and 6 months after starting treatment with gonadotropin-releasing analogues (GnRHa; T1). In both cases, treatment with GnRHa not only improved psychological functioning, but also resolved pathological eating behaviors. In fact, both adolescents reported quick restoring of healthy food habits with restricting eating behaviors as well as intensive exercise no longer needed after treatment with GnRHa. Therefore, pathological eating behaviors (e.g., food avoidance and weight loss) could be assessed as a dysfunctional coping strategy adopted to gain control over a body developing in an unwanted direction and to block irreversible physical pubertal changes. This psychopathological conceptualization of pathological eating behaviors in adolescents with gender dysphoria stresses the importance of providing, in selected cases, early medical intervention such as pubertal suppression with GnRHa. Mental health professionals should therefore perform a specific and detailed assessment on gender identity within the evaluation of apparent eating disorders in adolescents. Restrictive eating behaviors as well as the intense fear of gaining weight or of becoming fat may, in fact, be considered secondary to a gender dysphoria diagnosis instead of anorexia nervosa symptoms.