Difficulties of gender affirming treatment in trans women with BRCA1+ mutation: A case report.

Gender affirming treatment in transgender women is based on a combination of antiandrogens and estrogens, with the latter maintained over the long term. When prescribing these treatments, we must consider the possibility of developing estrogen-dependent breast cancer. In transgender women, a breast cancer incidence of 4.1 per 100,000 has been estimated, which would increase the risk by 46% in relation to cisgender men but decrease it by 70% in relation to cisgender women. It is known that certain gene mutations such as BRCA1 imply an increased risk of breast cancer, but at present the risk in transgender women with BRCA1 treated with estrogens is not well established. We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

The Impact of Gender-Affirming Hormone Therapy on Physical Performance.

CONTEXT: The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance. EVIDENCE ACQUISITION: MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. EVIDENCE SYNTHESIS: Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women. CONCLUSION: Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.

The influence of sex steroid treatment on insular connectivity in gender dysphoria.

BACKGROUND: Sex-specific differences in brain connectivity were found in various neuroimaging studies, though little is known about sex steroid effects on insular functioning. Based on well-characterized sex differences in emotion regulation, interoception and higher-level cognition, gender-dysphoric individuals receiving gender-affirming hormone therapy represent an interesting cohort to investigate how sex hormones might influence insular connectivity and related brain functions. METHODS: To analyze the potential effect of sex steroids on insular connectivity at rest, 11 transgender women, 14 transgender men, 20 cisgender women, and 11 cisgender men were recruited. All participants underwent two magnetic resonance imaging sessions involving resting-state acquisitions separated by a median time period of 4.5 months and also completed the Bermond-Vorst alexithymia questionnaire at the initial and final examination. Between scans, transgender subjects received gender-affirming hormone therapy. RESULTS: A seed based functional connectivity analysis revealed a significant 2-way interaction effect of group-by-time between right insula, cingulum, left middle frontal gyrus and left angular gyrus. Post-hoc tests demonstrated an increase in connectivity for transgender women when compared to cisgender men. Furthermore, spectral dynamic causal modelling showed reduced effective connectivity from the posterior cingulum and left angular gyrus to the left middle frontal gyrus as well as from the right insula to the left middle frontal gyrus. Alexithymia changes were found after gender-affirming hormone therapy for transgender women in both fantasizing and identifying. CONCLUSION: These findings suggest a considerable influence of estrogen administration and androgen suppression on brain networks implicated in interoception, own-body perception and higher-level cognition.

Implications of testosterone therapy on wound healing and operative outcomes of gender-affirming chest masculinization surgery.

The increased awareness of the transgender population and their medical needs has given rise to a wide array of gender-affirming surgeries and hormonal therapies. To better understand the implication of testosterone therapy on female-to-male gender-affirming mastectomies, we conducted a retrospective cohort study based on the medical histories of 170 transgender males operated on by a single surgeon over 18 years. One hundred and one (59.4%) patients received hormonal therapy. The average age of patients in the testosterone treatment group was 20.6 ± 5.3 (range 14-49) years. The median weight of resected breast tissue was 318 g (IQR 221-515) and 311.5 g (IQR 223-480) in patients treated with testosterone, compared to 380 g (IQR 225-735) and 370 g (IQR 240-700) in patients without testosterone treatment (for the right and left breast, respectively). Supplementary liposuction was performed in 35 patients, of whom 23 (64%) were treated with testosterone. Fifty-four patients (31.7%) experienced surgical complications, and 55.6% of complications were recorded in the group treated with testosterone. Forty-nine patients (28.8%) recorded their satisfaction using the Likert satisfaction scale; the average satisfaction was 4.86 ± 0.35 in the non-testosterone group and 4.63 ± 0.69 in the testosterone group. Opposing previous cohorts, we did not find a statistically significant association between testosterone and increased surgical complications in gender-affirming mastectomies. Possible explanations include our practice of avoiding testosterone therapy several weeks before the operation and vigorous hemostasis methods.

Endocrinological Approach to Adolescents with Gender Dysphoria: Experience of a Pediatric Endocrinology Department in a Tertiary Center in Turkey

Objective: A significant rise in the number of trans adolescents seeking medical interventions has been reported in recent years. The aim of this study was to report the clinical features, treatment, and follow-up of adolescents with gender dysphoria (GD) with our increased experience. Methods: Twenty-six male-to-female (MTF) and twenty-seven female-to-male (FTM) adolescents who were referred to the GD-outpatient clinic between 2016 and 2022 were reviewed. The clinical and laboratory findings of thirty transgender adolescents (15 FTM /15 MTF) who received medical intervention were evaluated retrospectively. Results: Most individuals (60.4%) were admitted between 2020 and 2022, and the remaining (39.6%) were admitted between 2016 and 2019. At the time of referral, median age was 16.3 years [interquartile range (IQR) 1.53; range 13.2-19.4] in 26 MTF, and 16.4 years (IQR 1.74; range 11.7-21.6) in 27 FTM adolescents. The median age at pubertal blockage with gonadotropin-releasing hormone analog and androgen receptor blocker was 16.4 years (IQR 1.4; range 11.7-17.8) in 22 adolescents (9 MTF, 13 FTM), and 17.4 years (IQR 1.4; range 15.5-19.4) in 6 MTF individuals, respectively. Cross-sex hormone therapy was commenced in 21 adolescents (12 MTF, 9 FTM) at the median age of 17.7 years (IQR 0.61; range 16-19.5). Fifteen individuals (8 MTF, 7 FTM) have been transferred to the adult endocrinology department in transition clinics. Conclusion: All treatments were generally well tolerated and effective, including bicalutamide, and no significant side effects were observed. Transition clinics played an important role in the better management of gender reassignment processes.

Changing trends in transgender demographics and morbidity: baseline data from a Spanish cohort.

The number of transgender people who request hormone treatment is increasing worldwide. We obtained base clinical and demographic information from transgender people treated at a specialised clinic in Spain (n =484) and studied changes over time. Transgender women treated in 2009-14 were older than those treated in 2015-20 (29years vs 17years), had a lower academic level and had higher anxiolytics consumption. Transgender men treated in 2009-14 were older than those treated later (27years vs 17years) and had a lower academic level. These trends reflect favourable changes in how the transgender population is treated by society and health services.

The metabolic effects of hormonal treatment in transgender males: Safety of the testosterone gender-affirming therapy.

BACKGROUND: Gender dysphoria is characterised by a sense of distress because of discordance between the self-perception of gender identity and the assigned sex. Hormonal treatment of transgender males uses testosterone to induce and preserve masculinisation. OBJECTIVE: The study investigated the safety of testosterone therapy in transgender males. METHODS: The present study used a retrospective file review of transgender male subjects who were treated with testosterone (initially transdermal testosterone gel and subsequently parenteral testosterone undecanoate) for at least 18 months and had subsequently achieved a serum testosterone level within the normal range of cisgender male counterparts. Changes in somatometric data and blood biomarkers were investigated. RESULTS: The mean testosterone serum levels after approximately 18 months of treatment were about 545 ng/dL (SD ± 94 ng/dL). There was a statistically significant rise in body mass index (𝜒d = +1.23 kg/m2) with a reduction in blood glucose (𝜒d = -5.33 mg/dL) as well as statistically significant increases in aspartate transaminase (𝜒d = +4.3 U/L), haemoglobin (𝜒d = +1.72 g/dL), and haematocrit (𝜒d = +4.76%). In contrast, there were no significant changes in the lipidaemic profile of the subjects. CONCLUSIONS: Treatment with testosterone is routinely used for the promotion of virilising physical changes in transgender males. However, the likelihood of adverse effects of continuous treatment is still unclear. This study contributed to the notion that achieving testosterone levels within the target range is a prerequisite for the safety of the gender-affirming treatment.

Perioperative Hormone Management in Gender-Affirming Mastectomy: Is Stopping Testosterone before Top Surgery Really Necessary?

BACKGROUND: Gender-affirming mastectomy, or "top surgery," has become one of the most frequently performed procedures for transgender and nonbinary patients. However, management of perioperative testosterone therapy remains controversial. Despite a lack of supporting evidence, many surgeons require cessation of testosterone before top surgery. This is the first study to compare complication rates in patients undergoing gender-affirming mastectomy with and without discontinuation of perioperative testosterone. METHODS: This retrospective review included patients undergoing top surgery by the senior author between 2017 and 2020. Reflecting a change in the senior author's practice, before May of 2019, all patients were required to discontinue testosterone before surgery; all patients treated after this point continued their testosterone regimens throughout the perioperative period. Patients were stratified according to testosterone regimen and perioperative hormone management, with demographic characteristics and postoperative outcomes compared among groups. RESULTS: A total of 490 patients undergoing gender-affirming mastectomy during the study period were included. Testosterone was held perioperatively in 175 patients and continued in 211 patients; 104 patients never received testosterone therapy. Demographic characteristics were similar among groups and there was no difference in rates of hematoma (2.9% versus 2.8% versus 2.9%, respectively; P = 0.99), seroma (1.1% versus 0% versus 1%, respectively; P = 0.31), venous thromboembolism (0% versus 0.5% versus 0%, respectively; P = 0.99), or overall complications (6.9% versus 4.3% versus 5.8%, respectively; P = 0.54). CONCLUSIONS: Our results demonstrate no difference in postoperative complication rates among groups. Whereas further investigation is warranted, our data suggest that routine cessation of testosterone in the perioperative period is not necessary for patients undergoing gender-affirming mastectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Gender identity: Current concepts and gender-affirming hormone therapy.

In the past five years, healthcare organisation for trans people in Spain has changed as laws intended to protect sexual and gender diversity have been put in place. As a result, endocrinologists are not only on the front lines (understood as prescribing and following up gender-affirming hormone therapy) but also coordinating multidisciplinary healthcare for these individuals. Advances in transgender medicine, the complexity of diverse trans identities and the impact of hormone therapy on quality of life and risk of middle- and long-term complications call for in-depth examination of a personalised biopsychosocial approach to trans people that requires specific training in this field of knowledge as well as updates on the concepts, terminology and drug treatments used.

Reflexiones en clave bioética al documento «Guía clínica de atención a menores transexuales, transgéneros y de género diverso» / Reflections in bioethics key to the document «Clinical guidelines for the care of transsexual, transgender and diverse gender minors»

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Continuation of Gender-affirming Hormones Among Transgender Adolescents and Adults.

INTRODUCTION: Concerns about future regret and treatment discontinuation have led to restricted access to gender-affirming medical treatment for transgender and gender-diverse (TGD) minors in some jurisdictions. However, these concerns are merely speculative because few studies have examined gender-affirming hormone continuation rates among TGD individuals. METHODS: We performed a secondary analysis of 2009 to 2018 medical and pharmacy records from the US Military Healthcare System. We identified TGD patients who were children and spouses of active-duty, retired, or deceased military members using International Classification of Diseases-9/10 codes. We assessed initiation and continuation of gender-affirming hormones using pharmacy records. Kaplan-Meier and Cox proportional hazard analyses estimated continuation rates. RESULTS: The study sample included 627 transmasculine and 325 transfeminine individuals with an average age of 19.2 ±â€…5.3 years. The 4-year gender-affirming hormone continuation rate was 70.2% (95% CI, 63.9-76.5). Transfeminine individuals had a higher continuation rate than transmasculine individuals 81.0% (72.0%-90.0%) vs 64.4% (56.0%-72.8%). People who started hormones as minors had higher continuation rate than people who started as adults 74.4% (66.0%-82.8%) vs 64.4% (56.0%-72.8%). Continuation was not associated with household income or family member type. In Cox regression, both transmasculine gender identity (hazard ratio, 2.40; 95% CI, 1.50-3.86) and starting hormones as an adult (hazard ratio, 1.69; 95% CI, 1.14-2.52) were independently associated with increased discontinuation rates. DISCUSSION: Our results suggest that >70% of TGD individuals who start gender-affirming hormones will continue use beyond 4 years, with higher continuation rates in transfeminine individuals. Patients who start hormones, with their parents' assistance, before age 18 years have higher continuation rates than adults.

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

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

Histologic Findings in Surgical Pathology Specimens From Individuals Taking Feminizing Hormone Therapy for the Purpose of Gender Transition.

CONTEXT.­: Transgender women experience health disparities in all areas of medicine. Within surgical pathology, knowledge gaps relating to the concepts of transgender care exist. Medical transition for transgender women and transfeminine persons may involve hormone therapy and/or surgery to feminize the body. Understanding the common histologic changes in specimens from feminizing surgeries, as well as other specimens from patients on feminizing hormone therapy, will aid surgical pathologists in providing better care to this unique patient population. OBJECTIVE.­: To summarize histologic findings in surgical pathology specimens from transgender women taking feminizing hormones. DATA SOURCES.­: A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender women from 1946 to 2019. CONCLUSIONS.­: Much of the literature to date describing histologic findings in transgender women comes from the examination of genitourinary specimens removed during feminizing surgeries. Common benign changes associated with feminizing hormone therapy include the development of acini and lobules in the breast, testicular tubular changes, and squamous metaplasia of the prostate and urethra. Neoplastic cases include breast adenocarcinoma and fibroepithelial lesions, testicular germ cell tumors, prostatic adenocarcinoma, anal squamous cell carcinoma, pituitary adenomas, and meningiomas. Additional studies assessing the findings in other organ systems as well as population-based studies assessing rates of neoplasia are needed. However, future research relies on engagement within the surgical pathology community as well as collaboration with clinicians and patients to achieve optimal results.

Histologic Findings in Surgical Pathology Specimens From Individuals Taking Masculinizing Hormone Therapy for the Purpose of Gender Transition.

CONTEXT.­: Transgender men and transmasculine persons experience a discordance between the female sex they were assigned at birth and their gender. They may choose to take hormone therapy and/or undergo surgery to masculinize the body. Understanding the common (and less common) histologic changes present in patients taking masculinizing hormones will empower pathologists to better serve this unique patient population. OBJECTIVE.­: To summarize histologic findings in surgical pathology specimens from persons taking masculinizing hormones as a part of gender transition. DATA SOURCES.­: A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender men from January 1946 to January 2021. CONCLUSIONS.­: Publication in this area has markedly increased in the last 2 decades. However, most of the studies identified were descriptive and case reports describing changes seen in specimens removed as a part of masculinizing surgical procedures. Benign histologic findings include stromal hyalinization and epithelial atrophy in the breast, polycystic ovarian syndrome-like changes in the ovary, and transitional cell metaplasia in the cervix. The most commonly reported neoplastic finding was adenocarcinoma of the breast, with rare cases of ovarian, endometrial, cervical, vaginal, pituitary, pancreatic, and cardiovascular neoplasia also reported. Ongoing research in this area is needed to better characterize the histologic findings in persons taking masculinizing hormones to provide a deeper understanding of the effect of these treatments on different tissues and facilitate better patient management.

Lipoprotein subtypes after testosterone therapy in transmasculine adolescents.

Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 µmol/L vs 2.7 ± 1.2 µmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men.