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(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 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(β) = 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(β) = 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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
We sought to determine the prevalence of pelvic pain reported by transmasculine individuals who had both a uterus and ovaries and were taking testosterone.
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.
Patients reported experiences of pelvic pain while on testosterone.
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).
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.
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.
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.

BACKGROUND: In the last decade, healthcare for the transgender population has increased considerably in many countries thanks to depathologization movements and the easier accessibility of medical assistance. The age at which they request to start gender-affirming hormones (GAHs) is increasingly younger. The cardiovascular risk associated with hormonal treatment is a novel research field, and the published studies are heterogeneous and inconclusive. Our objective is to determine the metabolic impact of GAHs in the transgender people treated in our Gender Identity Treatment Unit.
METHODS: We designed a pre-post study to analyze changes in anthropometric parameters (weight and body mass index), analytical determinations (fasting blood glucose, glycated hemoglobin, and lipoproteins), and blood pressure control in the transgender population treated with GAHs in Puerta del Mar University Hospital. These variables were collected before and one year after hormonal therapy.
RESULTS: A total of 227 transgender people were recruited between 2017 and 2020, 97 (40.09%) transwomen and 136 (59.91%) transmen. The average age at which GAHs began was 18 years. Weight, body mass index, and blood pressure increased significantly in both genders. Transmen showed a more atherogenic lipid profile, with a decrease in cholesterol LDL (p < 0.001) and an increase in triglycerides (p < 0.001). The risk of developing prediabetes or diabetes did not increase one year after treatment, although non-specific alterations in carbohydrate metabolism were detected, such as an increase in glycated hemoglobin in transmen (p = 0.040) and fasting blood glucose in transwomen (p = 0.008). No thromboembolic processes or cardiovascular events were reported during the first year of treatment.
CONCLUSIONS: In our setting, transgender people developed changes in their metabolic profiles in the first year after hormonal treatment. Both transmen and transwomen showed early alterations in lipid and carbohydrate metabolism, slight elevations in blood pressure, and a tendency to gain weight. This makes lifestyle interventions necessary from the beginning of GAHs.

UNASSIGNED: To describe barriers to care for a cohort of transgender and nonbinary (TNB) youth and examine factors associated with delays in receiving puberty blockers (PBs) or gender-affirming hormones (GAHs).
UNASSIGNED: We used longitudinal data from a prospective cohort of TNB youth seeking care at a multidisciplinary pediatric gender clinic between August 2017 and June 2018. We calculated the time between (i) initial clinic contact, (ii) phone intake, (iii) first medical appointment, and (iv) initiating PBs/GAHs. We estimated Kaplan-Meier curves for each time-to-care interval and used Cox regression models to estimate hazard ratios (HRs) for factors hypothesized to be barriers and facilitators of care.
UNASSIGNED: Our cohort included 104 youth aged 13-20 years. The median time from contacting the clinic to initiating PBs/GAHs was 307 days (range, 54-807). Lower income level, Medicaid insurance, and lack of family support were associated with longer times from contacting the clinic to completing the first medical appointment. In addition, older youth experienced longer times to first medical appointment relative to youth aged 13-14 years. Youth younger than 18 years of age who did not complete a mental health assessment before their first medical appointment experienced delays from first medical appointment to initiating PBs/GAHs (HR=0.44, 95% confidence interval, 0.22-0.88).
UNASSIGNED: Certain subsets of youth disproportionately experienced delays in receiving gender-affirming medications, and these factors varied by stage of care engagement. Given the association between gender-affirming care and improved mental health, identifying sociostructural and clinic-level barriers to care is critically important to facilitating more equitable access.

BACKGROUND: Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with growth and may impact final height (FH).
OBJECTIVE: To investigate the impact of ePS and GAH on FH in trans boys and trans girls.
METHODS: Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau\'s tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG).
RESULTS: The age at the start of PS was 12.37 ± 0.74 years in trans boys and 13.10 ± 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 ± 4.08 cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 ± 7.66 cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57 cm ± 3.1 (P = .168) and -0.98 cm ± 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62 cm ± 3.79, P = .056 and -2.35 cm ± 5.2, P = .051, respectively).
CONCLUSIONS: Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG.

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.

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.

Purpose: Few studies have assessed the effects of hormonal treatments such as gonadotropin-releasing hormone agonists (GnRHa) and gender-affirming hormones (GAH) on mental health outcomes in clinically referred gender-diverse young people from a younger age. Where this research has been conducted, findings have been mixed. This study investigated a cohort of young people before treatment, 1 year into GnRHa, and 1 year into GAH treatment to understand psychological and behavioral impacts over time. Methods: Thirty-eight young people (28 assigned female and 10 assigned male) referred to endocrinology, younger than 15 years at/beyond Tanner stage two, who received GnRHa followed by GAH treatment, were assessed in a retrospective analysis study. Young people completed the Youth Self Report (YSR), the Body Image Scale, and the Utrecht Gender Dysphoria Scale, while caregivers completed the Child Behavior Checklist (CBCL) and the Social Responsiveness Scale-2 at all time points. Results: Dissatisfaction with primary sexual characteristics (p = 0.02), gender dysphoria (p = 0.01), and social motivation (p = 0.04) improved significantly over time. Self-harm and suicidality also showed a general decrease. Caregivers reported a significant reduction in internalizing (p = 0.03) behaviors on the CBCL after GnRHa. Other subcategories of the YSR and CBCL were within normal ranges with no significant difference (p > 0.05). Conclusion: These findings demonstrate some improvements in psychological and behavioral outcomes in young people concurrently receiving psychosocial support and hormone treatment. Future research with larger and more diverse samples is warranted to further understand generalizability.