Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Management of breakthrough bleeding in transgender and gender diverse individuals on testosterone.

BACKGROUND: While many transgender and gender diverse individuals rapidly achieve amenorrhea on testosterone, emerging data have identified that breakthrough bleeding can occur in up to one-third of individuals with long-term use. Breakthrough bleeding can worsen dysphoria and patients may seek management to reattain amenorrhea. Because of this, there is a need to assess efficacy of management approaches. OBJECTIVE: The primary aim of the study was to evaluate methods used by patients and their providers to manage breakthrough bleeding which arises after 1 year of testosterone use. Secondary aims included describing the diagnostic approaches to breakthrough bleeding, and proposing an algorithm for classification and management of breakthrough bleeding in this patient population. STUDY DESIGN: This was an institutional review board-approved single tertiary center, retrospective chart review of transgender and gender diverse individuals on testosterone gender affirming hormone therapy who experienced breakthrough bleeding after 1 year of use. Charts were reviewed to determine patient characteristics, testosterone use, and breakthrough bleeding management approaches. RESULTS: Of the 96 individuals who had been on testosterone for 1 year and experienced breakthrough bleeding, 97% (n=93) engaged in at least 1 approach to management. The mean age at initiation of testosterone was 21.9 (standard deviation 5.4) and the median duration of time on testosterone was 54.5 months (interquartile range 33.5, 82). Only 16% (n=15) were using menstrual suppression at the time of their breakthrough bleeding episode. Breakthrough bleeding was successfully managed in 77 (79%), following between 1 and 4 attempted approaches. More than half of management attempts (63%) were successful on the first try. When management approaches were analyzed independently, the range of success associated with any particular approach was between 33% and 100%. Other than hysterectomy, which was fully successful at managing breakthrough bleeding, no approach was significantly better than no intervention. This was true both for individuals who did and did not bleed with missed testosterone doses. Regardless of what approach was used, after a failed attempt, the next attempt was successful in more than half of individuals. Of the 16 who underwent hysterectomy, 1 did so in part as a first line approach to manage breakthrough bleeding. CONCLUSION: In this study, use of medical management methods was not found to be superior to observation alone in the management of breakthrough bleeding. In the absence of data supporting superiority of any method, we recommend tailoring method attempts to patients' goals.

Evaluation and medical care of intersex and gender diverse youth.

While there is considerable overlap in the treatment of patients with intersex traits and differences in sex development (I/DSD) with transgender and gender diverse (TGD) youth, the initial medical evaluation varies significantly. I/DSD youth often present due to differences in genitalia development in infancy or pubertal development in adolescence, and this leads to comprehensive biochemical, radiologic, and genetic evaluation. TGD youth, however, tend to have typical development noted at birth and during puberty, but present with a gender identity that does not align with their sex assigned at birth and do not require evaluation for underlying pathology. For both I/DSD and TGD youth, the mainstays of treatment are to better align one's physical appearance to their gender identity. This review discusses the non-medical and medical interventions utilized in gender affirming care. A multidisciplinary team of mental health providers, pediatric medical providers, and surgeons is recommended for providing gender affirming care to both I/DSD youth and TGD youth and their families. Radiologists have an important role in initial evaluation of I/DSD youth and in ongoing monitoring of growth and bone mineral density during puberty induction in I/DSD and TGD youth.

Reproductive capacity after gender-affirming testosterone therapy.

Transgender and nonbinary people with female birth sex may utilize testosterone therapy for masculinization. Individuals interested in reproduction using their own gametes should be offered fertility preservation prior to starting testosterone. However, logistical and practical barriers prevent many from accessing fertility preservation options prior to starting testosterone. Some of these transmasculine and nonbinary individuals may later become interested in carrying a pregnancy or using their oocytes for reproduction after being on testosterone. Many questions remain about the reproductive impact of long-term masculinizing testosterone therapy. Emerging literature has documented pregnancies and successful assisted reproduction for some people after taking testosterone, but it is not known whether individuals can expect these successful outcomes. Testosterone appears to impact the reproductive tract, including the ovaries, uterus, and fallopian tubes, but the reversibility and functional impact of these changes also remain unclear. A greater understanding of the impact of masculinizing testosterone on reproductive capacity remains a priority area for future research.

Management of testosterone around ovarian stimulation in transmasculine patients: challenging common practices to meet patient needs-2 case reports.

Approximately 50% of transmasculine people use testosterone for gender affirmation, yet very little is known about the effects of testosterone on future reproductive capacity. Moreover, there are no data to guide fertility specialists on how to manage testosterone leading up to or during ovarian stimulation. Most clinics require cessation of testosterone prior to ovarian stimulation in this setting of no data; however, the current literature does suggest a potential increase in dysphoria with cessation of testosterone and during stimulation. This divergence begs the question of whether clinicians may be doing more harm than good by enacting this requirement. Here, we present two cases of transmasculine individuals who were on testosterone prior to stimulation and maintained their testosterone dosage throughout stimulation as proof of concept, followed by a discussion of current clinical practice and providing some rationale to support continuation of testosterone throughout stimulation.

Prevalence of pelvic pain in transgender individuals on testosterone.

BACKGROUND: Pelvic pain has been reported in transmasculine individuals taking testosterone. There is a need for further investigation to increase understanding of the prevalence and risk factors of this pain. AIM: We sought to determine the prevalence of pelvic pain reported by transmasculine individuals who had both a uterus and ovaries and were taking testosterone. METHODS: We conducted an institutional review board-approved retrospective study of all transmasculine individuals who had been taking testosterone for at least 1 year and had a uterus and ovaries at the time of testosterone initiation. Charts of participating patients were reviewed to determine patient characteristics, testosterone use, and pelvic pain symptoms both before and after initiation of testosterone. OUTCOMES: Patients reported experiences of pelvic pain while on testosterone. RESULTS: Of 280 individuals who had been on testosterone for at least 1 year, 100 (36%) experienced pelvic pain while on testosterone. Of those patients, 71% (n = 71) had not experienced pelvic pain prior to starting testosterone. There were 42 patients (15%) who had pelvic pain prior to starting testosterone, 13 (31%) of whom no longer experienced pain once starting testosterone. The median (IQR) age at initiation of testosterone was 22 (19-41) years and duration of testosterone treatment was 48 (27-251) months.Those patients who experienced pelvic pain while on testosterone were significantly more likely to have also reported pelvic pain prior to starting testosterone (29% vs 7%, P < .001). These patients were also more likely to have a pre-existing diagnosis of dysmenorrhea (27% vs 7%, P < .001), endometriosis (6% vs 2%, P = .049), or ovarian cysts and/or masses (12% vs 2% P < .001). Patients with pelvic pain were also more likely to have been on a menstrual suppression agent prior to and overlapping testosterone initiation (22% vs 12%, P = .03) and to have used menstrual suppression for longer durations (median [IQR] 18 [6-44] vs 8 [4-15] months, P = .04). CLINICAL IMPLICATIONS: Pelvic pain is common in transmasculine individuals who are initiating testosterone treatment, although testosterone has both positive and negative effects on pelvic pain in different individuals. STRENGTHS AND LIMITATIONS: The major strengths of this study included large numbers of patients, ability to assess for documentation of pelvic pain prior to testosterone, and ability to determine an actual prevalence of pelvic pain. Major limitations included the study being a retrospective analysis in a single tertiary care center, the limitations of clinical documentation, and the lack of a standard pelvic pain evaluation process. CONCLUSION: More than one-third of transmasculine patients with a uterus and ovaries had pelvic pain while on testosterone, with the majority reporting onset of pain after initiating testosterone.

Unmet need for gender-affirming care as a social determinant of mental health inequities for transgender youth in Aotearoa/New Zealand.

BACKGROUND: Past studies have demonstrated better mental health and well-being among transgender youth who had accessed gender-affirming care. However, few existing studies have assessed unmet need for gender-affirming care as a social determinant of mental health inequities. METHODS: Data on unmet need for gender-affirming care, distress and suicidality were analysed from the 2018 Counting Ourselves nationwide community-based survey of transgender people in Aotearoa/New Zealand. Associations between unmet need for gender-affirming care and mental health indicators were tested for transgender youth within the sample (aged 14-26 years; n = 608; Mage = 20.5). RESULTS: Transgender youth reported unmet needs ranging from 42% for gender-affirming hormone to 100% for feminizing surgeries and voice surgeries. Overall unmet need for gender-affirming care was associated with worse mental health. Trans men with an unmet need for chest reconstruction (84%) scored an average of 7.13 points higher on the K10 Psychological Distress Scale relative to those whose need had been met. Participants reporting unmet need for hormones (42%) had twice the odds (adjusted odds ratios = 2.01; CI = 1.02-3.98) of having attempted suicide in the last 12 months. CONCLUSIONS: Dismantling barriers to accessing gender-affirming care could play a crucial role in reducing mental health inequities faced by transgender youth.

Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms, Autism Spectrum Disorder, and Gender-Affirming Medical Treatment Status.

Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11-21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths' experiences, EF skill monitoring-and when appropriate, supports-should be considered for transgender youth.

An appraisal of current service delivery and future models of care for young people with gender dysphoria.

The clinical needs of young people with gender dysphoria (GD) have outpaced the capacity of health services to provide appropriate care. The study aimed to explore the interface of Paediatric Endocrinology and young people with GD, detailing the clinical characteristics and the clinical care provided, in order to inform future service development. Medical records of all young people with GD (n=91, 59 (65%) birth-assigned females and 32 (35%) birth-assigned males) referred to Paediatric Endocrinology during 2011-2019 for puberty suppression were reviewed. Median age at initial assessment was 14.6 years (range 8.8-17.6 years). There was a threefold increase from 2016 (n=22) to 2019 (n=73). Mental health disorders were present in 34 (37%) and autistic spectrum disorder in 21 (23%), while 54 (59%) had at least one comorbidity. Sixty-four (70%) young people fulfilled the criteria for consideration of fertility preservation, with 6 (9%) of them preserving their gametes. Seventy-nine (87%) young people commenced treatment with gonadotrophin-releasing hormone analogue, at a median age of 14.8 years (range 9.7-18.0 years). Six (8%) of those discontinued treatment, following a median duration of 6 months (range 6-18 months). Forty-one young people commenced gender-affirming hormones. One (2%) of those who started gender-affirming hormones discontinued treatment.Conclusions: We have witnessed increasing numbers of young people with GD attending Paediatric Endocrinology, with an over-representation of comorbidities, necessitating provision of an individualised approach to treatment. Addressing young people's acceptability of fertility services and ongoing close collaboration between endocrinology and mental health professionals require innovative models of multidisciplinary care. What is Known: • A worldwide increase in presentation of gender dysphoria has been mirrored in our service, with majority assigned female at birth and post-pubertal. • An over-representation of comorbidities exists, notably mental health disorders and autistic spectrum disorder. What is New: • Coordination of interprofessional care to meet complex needs, at an individual level, while improving efficiency of working, at a systemic level, can be met by the development of specialist centres. • The reasons for low uptake of fertility services demand further exploration.

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.

Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey.

PURPOSE: We undertook a study to assess the associations between barriers to insurance coverage for gender-affirming hormones (either lack of insurance or claim denial) and patterns of hormone use among transgender adults. METHODS: We used data from the US Transgender Survey, a large national sample of 27,715 transgender adults, collected from August to September 2015. We calculated weighted proportions and performed multivariate logistic regression analyses. RESULTS: Of 12,037 transgender adults using hormones, 992 (9.17%) were using nonprescription hormones. Among insured respondents, 2,528 (20.81%) reported that their claims were denied. Use of nonprescription hormones was more common among respondents who were uninsured (odds ratio = 2.64; 95% CI, 1.88-3.71; P <.001) or whose claims were denied (odds ratio = 2.53; 95% CI, 1.61-3.97; P <.001). Uninsured respondents were also less likely to be using hormones (odds ratio = 0.37; 95% CI, 0.24-0.56; P <.001). CONCLUSIONS: Lack of insurance coverage for gender-affirming hormones is associated with lower overall odds of hormone use and higher odds of use of nonprescription hormones; such barriers may thus be linked to unmonitored and unsafe medication use, and increase the risks for adverse health outcomes. Ensuring access to hormones can decrease the economic burden transgender people face, and is an important part of harm-reduction strategies.

Health care provider perceptions of fertility preservation barriers and challenges with transgender patients and families: qualitative responses to an international survey.

PURPOSE: To examine provider perceptions of practice behaviors and barriers related to fertility counseling, fertility preservation, and family building among transgender patients. METHODS: Participants were medical and mental health professionals who treat adult and youth transgender patients. Recruitment occurred online and in person, via professional listservs for transgender professionals, conferences, and gender clinics. From August-November 2017, 110 participants representing nine countries responded to four open-ended questions included on a survey related to provider practice behaviors and perceived barriers to fertility counseling, fertility preservation, and family building with transgender patients. Thematic coding analysis was used to identify themes. RESULTS: Multiple themes were identified including the following: access and cost issues; urgency for gender-affirming treatment; patient maturity and inability to make future-oriented decisions; and provider-related challenges pertaining to knowledge, role, and general lack of information in the nascent field of transgender reproductive health. CONCLUSION(S): This study yielded insights into practice behaviors, challenges, and perceived barriers to fertility counseling with transgender individuals and can serve as a basis for intervention development to optimize clinical practices with this population.

Prospective Evaluation of Self-Reported Aggression in Transgender Persons.

BACKGROUND: Although research on the relation between testosterone and aggression in humans is inconclusive, guidelines (including the World Professional Association for Transgender Health Standards of Care, edition 7) have warned for an increase in aggression in transgender men taking testosterone treatment. AIMS: To investigate the association between levels of testosterone and aggression in treatment-seeking transgender people and explore the role of mental health psychopathology (anxiety and depressive symptoms) and social support in aggression in this population. METHODS: Every transgender person invited for assessment at a national transgender health clinic in the United Kingdom during a 3-year period (2012-2015) completed self-report measures for interpersonal problems, including levels of aggression (Inventory of Interpersonal Problems [IIP-32]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), social support (Multidimensional Scale of Perceived Social Support), and experiences of transphobia before and 1 year after the initiation of gender-affirming hormonal therapy. Correlations between prospective scores for the IIP-32 factor "too aggressive" and prospective levels of sex steroids, prospective psychological (HADS), and baseline psychosocial measurements were tested. OUTCOMES: Prospective scores for the factor "too aggressive" were not correlated to prospective serum testosterone levels. RESULTS: Results of 140 people (56 transgender men, 84 transgender women) were analyzed. A prospective increase in scores for the factor "too aggressive" of the IIP-32 in transgender men 1 year after being treated with testosterone treatment or a decrease of the IIP-32 aggression scores in transgender women 1 year after gender-affirming hormonal therapy was not found. However, a positive correlation was found between increasing HADS anxiety scores and increasing scores for the IIP-32 "too aggressive" score in the entire study population and a positive correlation with lower support from friends in transgender women. CLINICAL IMPLICATIONS: Hormone-prescribing physicians can be reassured that the long-term administration of testosterone in transgender men does not increase aggressive behavior. STRENGTHS AND LIMITATIONS: This is the 1st prospective study to assess the effect of gender-affirming hormonal care on aggression. Limitations included the use of different laboratories, the use of a patient-reported outcome measure, and the lack of aggression subtypes. CONCLUSIONS: Testosterone therapy was not associated with an increase in levels of aggression in transgender men or a decrease in aggressive behavior in transgender women on antiandrogen and estrogen therapy, but other psychological and/or social factors, such as anxiety levels, appear to contribute to self-reported aggression in transgender people. Defreyne J, T'Sjoen G, Bouman WP, et al. Prospective Evaluation of Self-Reported Aggression in Transgender Persons. J Sex Med 2018;15:768-776.

The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets.

BACKGROUND: Over the past decade, the number of people referred to gender identity clinics has rapidly increased. This raises several questions, especially concerning the frequency of performing gender-affirming treatments with irreversible effects and regret from such interventions. AIM: To study the current prevalence of gender dysphoria, how frequently gender-affirming treatments are performed, and the number of people experiencing regret of this treatment. METHODS: The medical files of all people who attended our gender identity clinic from 1972 to 2015 were reviewed retrospectively. OUTCOMES: The number of (and change in) people who applied for transgender health care, the percentage of people starting with gender-affirming hormonal treatment (HT), the estimated prevalence of transgender people receiving gender-affirming treatment, the percentage of people who underwent gonadectomy, and the percentage of people who regretted gonadectomy, specified separately for each year. RESULTS: 6,793 people (4,432 birth-assigned male, 2,361 birth-assigned female) visited our gender identity clinic from 1972 through 2015. The number of people assessed per year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women (transmen). The percentage of people who started HT within 5 years after the 1st visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage of people who underwent gonadectomy within 5 years after starting HT remained stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of transwomen and 0.3% of transmen who underwent gonadectomy were identified as experiencing regret. CLINICAL IMPLICATIONS: Because the transgender population is growing, a larger availability of transgender health care is needed. Other health care providers should familiarize themselves with transgender health care, because HT can influence diseases and interact with medication. Because not all people apply for the classic treatment approach, special attention should be given to those who choose less common forms of treatment. STRENGTHS AND LIMITATIONS: This study was performed in the largest Dutch gender identity clinic, which treats more than 95% of the transgender population in the Netherlands. Because of the retrospective design, some data could be missing. CONCLUSION: The number of people with gender identity issues seeking professional help increased dramatically in recent decades. The percentage of people who regretted gonadectomy remained small and did not show a tendency to increase. Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. J Sex Med 2018;15:582-590.

Breast and reproductive cancers in the transgender population: a systematic review.

BACKGROUND: The medical transition undergone by a transgender person may influence their risk of breast or reproductive cancer. OBJECTIVES: To assess breast and reproductive cancer prevalence in the transgender population. To elucidate any associations between gender-affirming hormones and risk of these cancers. SEARCH STRATEGY: Following registration of review protocol with PROSPERO, five databases were searched. SELECTION CRITERIA: Included studies investigated breast, ovarian, uterine, cervical, vaginal, neovaginal, testicular and prostate cancer in the transgender population. Secondary studies, opinions, editorials and conference abstracts were excluded. No date, language or setting restrictions were applied. DATA COLLECTION AND ANALYSIS: Two reviewers conducted literature searches and applied inclusion and exclusion criteria to the results. Studies were categorised, aggregated and analysed by study population (transmen/transwomen) and type of cancer. MAIN RESULTS: The literature search produced 228 articles; 43 were included. The overall evidence quality was very low to low. In transgender women, 20 breast cancer cases, two neovaginal cancer cases, one testicular cancer case and eight prostate cancer cases were reported. In transgender men, 18 breast cancer cases, five ovarian cancer cases, four uterine/cervical cancer cases and one vaginal cancer case were reported. CONCLUSIONS: There is insufficient evidence to estimate breast or reproductive cancer prevalence in the transgender population. Gender-affirming hormones have not been shown to affect cancer risk, but there is a clear need for well-designed, robust studies to confirm or refute this. FUNDING: This study was undertaken as an education dissertation. No funding was received. TWEETABLE ABSTRACT: Little is known about the impact of gender-affirming hormones on breast or reproductive cancers in trans people.

Required Mental Health Evaluation Before Initiating Gender-Affirming Hormones: Trans and Nonbinary Perspectives.

Purpose: Gender-affirming hormones (hormones)-the use of sex hormones to induce desired secondary sex characteristics in transgender and nonbinary (TGNB) individuals-are vital health care for many TGNB people. Some hormone providers require a letter from a mental health provider before hormone initiation. We explore the perspectives of TGNB individuals regarding the impact of the letter requirement on their experience of care. Methods: We conducted semistructured interviews with 21 TGNB individuals who have sought or are receiving hormones. We purposively sampled respondents who were (n=12) and were not (n=8) required to provide a letter. An Advisory Board of transgender individuals guided the methodology. Interviews were transcribed verbatim and coded both inductively and deductively. Results: We identified three themes related to the letter requirement: (1) Mental health: While participants appreciated the importance of therapy, the letter requirement did not serve this purpose; (2) Trans identity: The process of obtaining a letter created doubt in participants' own transness, along with a resistance to the pathologization and conflation of mental illness with transness; and (3) Care relationships: The letter requirement negatively impacted the patient-provider relationship. Participants felt the need to self-censor or to perform a version of transness they thought the provider expected; this process decreased their trust in care professionals. Conclusion: A letter requirement did not improve mental health and had several negative consequences. Removal of this requirement will improve access to hormones and may paradoxically improve mental health.

Gender-Diverse Youth with Turner Syndrome: Special Management Considerations.

Turner syndrome (TS) is a sex chromosome abnormality characterized by short stature and primary hypogonadism with increased risk for cardiovascular disease, osteopenia, metabolic syndrome, diabetes mellitus, abnormal liver enzymes, and impairment of nonverbal learning skills. Gender-diverse youth include youth who have a gender identity that is different from their sex assigned at birth. They have an increased risk of suicidality, which is decreased in those who receive gender-affirming care. There have been no prior reports on the association or management of gender-diverse youth with TS. We describe 3 cases of gender-diverse youth with TS that highlight the importance of discussing gender identity in patients with hypogonadism in need of sex hormone replacement. Goals of care should be discussed to determine whether estrogen or testosterone replacement aligns best with gender identity. If a patient chooses to start testosterone, special considerations of risks such as erythrocytosis, osteopenia, and cardiovascular disease should be discussed in relation to their TS.

Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial.

Purpose: Transgender women are disproportionately affected by HIV and are underutilizing preexposure prophylaxis (PrEP). The lower uptake of PrEP by transgender women may be, in part, owing to the perception that taking PrEP may lower the efficacy of gender-affirming hormone therapy (GAHT) or to provider concerns that GAHT may lower the efficacy of PrEP. Methods: DISCOVER was a randomized, double-blind, noninferiority trial comparing emtricitabine (FTC, F) and tenofovir alafenamide (F/TAF) versus emtricitabine and tenofovir disoproxil fumarate (F/TDF) as PrEP among transgender women and cisgender men who have sex with men (MSM). This nested substudy of the DISCOVER trial compared the exposure of the active intracellular metabolites of FTC and tenofovir (TFV), FTC triphosphate (FTC-TP) and TFV diphosphate (TFV-DP), in peripheral blood mononuclear cells (PBMC) among transgender women receiving GAHT versus MSM within the F/TAF and F/TDF groups. Results: Our results demonstrate that TFV-DP and FTC-TP levels in PBMC were comparable between transgender women on GAHT and MSM receiving F/TAF, and between transgender women on GAHT and MSM receiving F/TDF. TFV-DP concentrations remained above the EC90 of 40 fmol/106 cells across all groups. No clinically significant drug-drug interactions of GAHT were observed with either F/TAF or F/TDF in this subanalysis. Conclusions: These findings are consistent with the clinical pharmacology of GAHT, FTC, TDF, and TAF reported in previous studies, and support the continued use of F/TAF and F/TDF for PrEP in transgender women.Clinicaltrials.gov registration number: NCT02842086.

A Mouse Model to Investigate the Impact of Gender Affirming Hormone Therapy with Estradiol on Reproduction.

Gender-affirming hormone therapy (GAHT) can help transgender and/or gender diverse (TGD) individuals achieve emobidment goals that align with their transition needs. Clinical evidence from estradiol (E)-GAHT patients indicate widespread changes in tissues sensitive to E and testosterone (T), particularly in the reproductive system. Notably, E-GAHTs effects on hormones and reproduction vary greatly between patients. With the goal of informing clinical research and practice for TGD individuals taking E, this study examines intact male mice implanted with capsules containing one of three different E doses (low 1.25 mg; mid 2.5 mg; high 5 mg), or a blank control capsule. All E-GAHT doses suppress T and follicle stimulating hormone levels while elevating E levels. Only the high E-GAHT dose significantly supresses luteinizing hormone levels. All E-GAHT doses affect epididymis tubule size similarly while seminiferous tubule morphology and bladder weight changes are dose-dependent. E-GAHT does not alter the presence of mature sperm, though E-exposed sperm have altered motility. These data represent the first evidence that mouse models offer an effective tool to understand E-GAHTs impact on reproductive health and the dose-dependent effects of this model permit examinations of diverse patient outcomes.

How do Italian pediatric endocrinologists approach gender incongruence?

BACKGROUND: Gender incongruence (GI) is a term used to describe a marked and persistent incompatibility between the sex assigned at birth (SAAB) and the experienced gender. Some persons presenting with GI experience a severe psychological distress defined as gender dysphoria (GD).. Although the prevalence of GI is probably underestimated, recently a great increase in numbers of transgender and gender diverse (TGD) youths presenting at the gender clinics has been registered. After a careful multidisciplinary evaluation and upon acquisition of informed consent from the youth and the legal guardian(s), puberty suppression can be started in TGD youths, followed by the addition of gender affirming hormones (GAH) by the age of 16 years. Although Italian specific guidelines are available, their application is often complex because of (among other reasons) lack of specialized centers and healthcare professional with experience in the field and the regional differences within the Italian healthcare system. MAIN BODY: To investigate the care offered to TGD youths across Italy, we proposed a survey of 20 questions to the directors of the 32 Italian Centers of pediatric endocrinology participating to the Study Group on Growth and Puberty of the Italian Society of Pediatric Endocrinology (ISPED). Eighteen pediatric endocrinologists representative of 16 different centers belonging to 11 different regions responded to the survey. In the large majority of centers TGD youths are taken in charge between the age of 12 and 18 years and at least three healthcare professional are involved. Most of Italian pediatric endocrinologists follow only a very limited number of TGD youths and reference centers for TGD youths are lacking. CONCLUSION: There is an urgent need for gender clinics (homogeneously distributed on the national territory) where TGD youths can access high standard care.