Short-Term Changes in Bone Metabolism Among Transgender Men Starting Gender-Affirming Hormone Therapy: A Systematic Review and Meta-analysis.

Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40-0.83; p < 0.0001; I2 = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term.

Safe and supportive prescribing in transgender and non-binary patients with cancer.

Global prevalence rates for transgender individuals vary with estimates ranging from 0.3% to 1%, translating to a potential global population of 24.3 million to 81 million. It is estimated that one in two people will develop cancer in their lifetime. Gender-affirming hormone therapy (GAHT) is a common medical intervention for transgender and non-binary individuals. GAHT requires careful consideration for concurrent medical care due to potential drug interactions and physiological changes. A multi-disciplinary team with expertise in transgender health, oncology and pharmacy met to develop a document summarizing current knowledge on the topic for practical use. The team included trans and non-binary authors who shaped the document's language and focus. The document gives a status update on the current understanding of GAHT and how this may intersect with the safe prescribing of systemic anti-cancer therapies (SACT). The document underwent multiple review stages including internal review, review by the British Oncology Pharmacy Association (BOPA) EDI Subcommittee and, finally, BOPA Executive Committee review and final approval. Key recommendations of this document include the use of inclusive and effective communication, vigilant monitoring of kidney function and cardiovascular health, and considerations for hormone receptor-positive cancers. The document also recognizes the multidisciplinary nature of transgender healthcare and where this relates to social prescribing.

Androgenetic alopecia incidence in transgender and gender diverse populations: A retrospective comparative cohort study.

BACKGROUND: Androgenetic alopecia (AGA) is a significant challenge for many transgender and gender diverse (TGD) patients, but the rate of AGA among TGD patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients has not yet been studied on a large scale. OBJECTIVE: We examined the incidence of AGA among TGD patients receiving GAHT compared to cisgender patients. METHODS: Retrospective cohort study using electronic health records from 37,826 patients seen at Fenway Health between August 1, 2014, and August 1, 2020. Crude and adjusted incidence rate ratios (aIRR) for AGA were calculated using Poisson regression. RESULTS: TGD patients receiving masculinizing GAHT had aIRR 2.50, 95% CI 1.71-3.65 and 1.30, 95% CI 0.91-1.86 compared to cisgender women and cisgender men, respectively. The rate of AGA for TGD patients receiving feminizing GAHT was not significantly different compared to cisgender men but was significantly increased compared to cisgender women (aIRR 1.91, 95% CI 1.25-2.92). LIMITATIONS: Inability to determine causation and limited generalizability. CONCLUSION: TGD patients receiving masculinizing GAHT have 2.5 times the rate of AGA compared to cisgender women, whereas TGD patients on feminizing GAHT did not have a significantly increased rate of AGA compared to cisgender men.

Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy.

OBJECTIVE: Gender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals. METHODS: This is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes. RESULTS: There were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status. CONCLUSION: Both the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

PURPOSE OF REVIEW: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models. RECENT FINDINGS: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women.

OBJECTIVE: To investigate the pharmacokinetics of 17ß-estradiol (E2) administered orally versus those of 17ß-E2 administered sublingually in transgender women. METHODS: Single doses of 17ß-E2 were administered orally (1 mg) to 10 transgender women and then sublingually (1 mg) after a 1-week washout period. Blood samples were collected at baseline (0 hour) and at 1, 2, 3, 4, 6, and 8 hours after dosing. The samples were frozen and analyzed using liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay. RESULTS: The results demonstrated that sublingual E2 had a significantly higher peak serum E2 concentration of 144 pg/mL, measured using LC-MS/MS, compared with an oral E2 concentration of 35 pg/mL, measured using LC-MS/MS (P = .003). Sublingual E2 peaked at 1 hour and oral E2 peaked at 8 hours, as measured using LC-MS/MS. The area under the curve (AUC) (0-8 hours) for sublingual E2, measured using LC-MS/MS, was 1.8-fold higher than the AUC (0-8 hours) for oral E2, measured using LC-MS/MS. Additionally, sublingual E2 was found to have an increased E2-to-estrone ratio at all time points (1.1 ± 1.0 vs 0.7 ± 0.4, P ≤ .0001), the clinical significance of which is unclear. CONCLUSION: Oral E2 administered sublingually has a different pharmacokinetic profile, with higher serum E2 levels and AUC (0-8 hours) than traditionally administered oral E2. Multidaily dosing may be necessary to suppress testosterone levels with sublingual E2. The appropriate dosing, efficacy, and safety of sublingual E2, compared with those of other E2 preparations, are unknown.

Which U.S. States' Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Gender-Affirming Genital Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Services.

BACKGROUND: To date, a comprehensive state-by-state assessment of transgender transition-related health care coverage for gender-affirming hormone therapy (GAHT) and genital gender-affirming surgery (GAS) has not been reported. AIMS: The aims of this study were 1) to verify which U.S. states' Medicaid systems do/do not cover GAHT and GAS; 2) to assess the ease/difficulty for patients to determine whether GAHT and GAS are Medicaid-covered benefits; and 3) to understand possible state-related predictors of Medicaid coverage for gender-affirming care. METHODS: We reviewed the official Medicaid Handbook and website for all 51 states (+D.C.) and 5 territories to confirm whether GAHT and GAS are covered benefits. When indeterminate, we called the Medicaid office in each state, and for many, Medicaid managed care organizations (MCOs), and individual in-state providers, to confirm coverage. We recorded our experiences, number of, and duration of phone calls to confirm coverage. OUTCOMES: The main outcome was a definitive answer from the state/territory's Medicaid program or MCOs regarding whether GAHT and GAS are/are not covered benefits. Secondary outcome measures included responses we received and the total number/duration of phone calls necessary to confirm coverage. RESULTS: Only 12 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAHT in their Medicaid Handbook/webpages. We confirmed that 34 of 51 state Medicaid programs do cover GAHT, whereas 9 of 51 states' and 2 of 5 territories' do not. We could not confirm coverage of GAHT in 8 of 51 states and 3 of 5 territories. Only 26 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAS in their Medicaid Handbook/webpages. We confirmed that 25 of 51 state Medicaid programs do cover GAS, whereas 22 of 51 states' and 3 of 5 territories' do not. We could not confirm coverage of GAS in 4 of 51 states and 2 of 5 territories. Up to 12 calls, lasting up to 125 minutes, were required to confirm coverage for GAHT/GAS. CLINICAL IMPLICATIONS: Our findings indicate that important health care access barriers/disparities exist today and warrant improvement. STRENGTHS & LIMITATIONS: To our knowledge, this is the most comprehensive assessment of transgender transition-related health care coverage. Limitations include possible bias, as it could be that we were more persistent than actual patients would be to determine service coverage, and a lack of specificity regarding which specific hormone formulations or procedures are/are not covered. CONCLUSION: Our findings show that only 34 of 51 (67%) states' Medicaid programs include GAHT and 25 of 51 (49%) include GAS as covered benefits. Our experience suggests that the process to confirm coverage can be especially time-consuming and frustrating for patients. Zaliznyak M, Jung EE, Bresee C, et al. Which U.S. States' Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Genital Gender-Affirming Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Service. J Sex Med 2021;18:410-422.

Androgen Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males.

Ovarian function is controlled by pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn are governed by gonadotropin releasing hormone (GnRH) secreted from the brain. A fundamental principle of reproductive axis regulation is negative feedback signaling by gonadal sex steroids back to the brain to fine-tune GnRH and gonadotropin secretion. Endogenous negative feedback effects can be mimicked by exogenous steroid treatments, including androgens, in both sexes. Indeed, a growing number of clinical and animal studies indicate that high levels of exogenous androgens, in the typically male physiological range, can inhibit LH secretion in females, as occurs in males. However, the mechanisms by which male-level androgens inhibit GnRH and LH secretion still remain poorly understood, and this knowledge gap is particularly pronounced in transgender men (individuals designated female at birth but identifying as male). Indeed, many transgender men take long-term gender-affirming hormone therapy that mimics male-level testosterone levels. The impact of such gender-affirming testosterone on the reproductive axis, both at the ovarian and neuroendocrine level, is a long-understudied area that still requires further investigation. Importantly, the few concepts of androgen actions in females mostly come from studies of polycystic ovary syndrome, which does not recapitulate a similar androgen milieu or a pathophysiology of inhibited LH secretion as occurs in testosterone-treated transgender men. This review summarizes clinical evidence indicating that exogenous androgens can impair neuroendocrine reproductive function in both female individuals and transgender men and highlights emerging experimental data supporting this in recently developed transgender rodent models.

Monitoring and reporting of adverse effects of testosterone prescribing for gender affirmation at general practice clinics - Data from the PUSH! Audit.

Introduction: Prescribing testosterone for gender affirming hormone therapy (GAHT) has been increasing in Australia with much of this practice done by general practitioners (GPs) and there are current AusPATH guidelines on how this can be done appropriately. There has been limited data collected from GPs about how well these patients are monitored and the adverse effects (AEs) that are experienced by this population of patients. Objectives: The primary objective of this study was to collect data about monitoring and adverse effects of GAHT provided in GP settings. Methods: The PUSH! Audit was a cross-sectional study that collected data from 9 GP Clinics across 5 Australian cities who provided GAHT with testosterone. Data was also collected about cisgender men who were prescribed testosterone for testosterone deficiency (TD) as a comparison group (n = 209). Results: The patients in the GAHT group (n = 277) tended to be younger (29.8 vs 54.9), with significant prevalence of smoking (21.8%) and anxiety/depression (37.2%) although this was not significantly higher that the comparison group. Most of the GAHT group had a testosterone level recorded in their file (90.6%) and the most common route of administration of testosterone was by intra-muscular injection (89.9%). The testosterone levels were mainly in the target range for males (75.7%) with only a small percentage registering levels above the target range (5.6%). Of the measured AEs, whilst there were significant prevalence of liver abnormalities and hypercholesterolemia, this was not significantly different to the TD group. The hypertension prevalence was lower in the GAHT group. Of the reported AEs, acne (10.1%) and balding (4.7%) were the only two AEs that were significantly reported. Conclusion: This study shows that GAHT with testosterone can be provided effectively in general practice with high levels of success and very low levels of AEs.

Gallbladder disease in transgender individuals: associations with gender-affirming hormone therapy.

Background: Transgender individuals frequently undergo gender-affirming hormone therapy (GAHT) during their gender transition which plays a vital role in gender identity affirmation. Cholelithiasis, a common condition affecting 10-15% of the US population, has been linked to estrogen therapy in cisgender women. Despite the fact that hormonal profiles achieved after GAHT are not always identical to cisgender individuals, the effects of GAHT on gallbladder disease (GBD) risk have not been evaluated in transgender populations. This research aims to address this gap utilizing a large nationwide database. Methods: The study analyzed medical records data from the TrinetX database from 52,847 trans men and 38,114 trans women. Four cohorts were created: trans women and men either receiving either hormone therapy or no intervention. Descriptive statistics were calculated before matching to estimate disease burden. The groups were then propensity score matched on known risk factors (age, race, BMI, etc.) and rates of GBD were compared. Results: Before matching, trans women on hormone therapy (TWHT) had a significantly higher 10-year GBD probability than those naïve to therapy (TWNI) (4.69% vs 1.88%). For trans men, there was no significant difference in 10-year rates between those on therapy (TMHT) and those not (TMNI) (3.15% vs 3.87%). Cholecystectomy rates were significantly higher for TWHT than TWNI (1.10% vs. 0.57%), but similar between TMHT and TMNI (0.95% vs. 1.10%). After accounting for risk factors, TWHT had increased GBD risk (HR 1.832), while TMHT showed no significant change. Discussion: This study suggests a link between estrogen GAHT and increased GBD risk in transgender women. Notably, testosterone GAHT did not offer protection against GBD in transgender men, contrary to expectations. This study is, to our knowledge, the first to describe the burden of GBD in the transgender population and to investigate the effects of GAHT on GBD risk.

Priorities for efficacy trials of gender-affirming hormone therapy with estrogen: collaborative design and results of a community survey.

PURPOSE: Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E. METHODS: Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen. RESULTS: A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated "extremely important" or "very important" were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated "highest priority" or "high priority" among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration. CONCLUSION: The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

Impact of Distinct Antiandrogen Exposures on the Plasma Metabolome in Feminizing Gender-affirming Hormone Therapy.

CONTEXT: The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism. OBJECTIVE: Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described. METHODS: Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns. RESULTS: We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant "sex- and age-related" pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile. CONCLUSION: Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT.

Impact of Gender-Affirming Hormonal Therapy on Cardiovascular Risk Factors in Transgender Health: An Updated Meta-Analysis.

Background: Gender-affirming hormone therapy (GAHT) is common among transgender individuals, but its impact on lipid profile and cardiovascular health is not well studied. Objectives: The authors performed a systematic review and meta-analysis of existing literature to assess the impact of GAHT on lipid profiles and metabolic cardiovascular risk factors in transgender individuals. Methods: Online databases including MEDLINE/PubMed, Embase, and Cochrane Central registry were searched to find studies on lipid profile changes in women who are transgender, also referred to as transfeminine (TF), and men who are transgender, also referred to as transmasculine (TM) before and after GAHT. Baseline comorbidities were analyzed using descriptive statistics, and R-statistical software was used to analyze the mean difference in lipid profile change between the two cohorts (pre- and post-GAHT therapy) including transgender patients. Results: Overall, 1,241 TM and 992 TF patients were included from 12 observational studies and 12 randomized controlled trials. The mean age among TM and TF was 28 years and 30 years, respectively. The mean follow-up duration (including pre- and post-GAHT therapy) was 28 months in TM patients and 39 months in TF patients. When compared to baseline measures, TM patients had a significant increase in low-density lipoprotein, triglyceride levels, and total cholesterol while high-density lipoprotein levels decreased. In TF patients, there was a significant increase in triglyceride levels. Conclusions: GAHT affects lipid profiles in transgender patients; however, additional studies are needed to determine how these changes impact clinical outcomes.

Reproductive Considerations in the Transgender and Gender Diverse Population: A Review.

Many transgender and gender diverse (TGD) individuals will be considering gender-affirming treatments during their reproductive lifespan. These medically necessary treatments have a negative impact on reproductive potential. All TGD individuals should be counseled regarding fertility. Options for fertility preservation for individuals who have undergone puberty include mature oocyte, embryo, and sperm cryopreservation. In prepubertal individuals, ovarian tissue cryopreservation may be considered, but testicular tissue cryopreservation remains experimental only. While there have been advances in the technology and standardization of reproductive health care for this population, many gaps remain in our knowledge which require further research.

Incidence of Type 2 Diabetes Mellitus in Transgender Individuals Undergoing Gender Affirming Hormonal Therapy: A Systematic Review.

Gender-affirming hormonal therapy (GAHT), which includes estrogen, testosterone, androgen agonists, is commonly used in transgender individuals to change their secondary sexual characteristics to align with their gender identity. However, this treatment could result in metabolic side effects that could increase the chances of acquiring type 2 diabetes mellitus. Thus, this study aims to compare differences in body mass index (BMI), insulin resistance, and the incidence of type 2 diabetes mellitus between cisgender and transgender individuals undergoing GAHT. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review searching through PubMed, Google Scholar, Medline (Medical Literature Analysis and Retrieval System Online), and ResearchGate for articles published between 2014 and 2024. The final search was conducted in February 2024. Out of the 3,934 articles reviewed, 11 were selected, focusing on insulin sensitivity/resistance, diabetes incidence, and BMI changes with GAHT. Although our result findings did not show clear evidence of increased diabetes incidence among GAHT patients, it was observed that GAHT does increase BMI and insulin resistance in transgender individuals. Notably, compared to transgender men, transgender women on GAHT were found to be more prone to insulin resistance. We recommend regularly monitoring insulin sensitivity parameters and HbA1c during GAHT to monitor metabolic side effects. Further research and more clinical trials are needed to confirm the GAHT's impact on insulin resistance and to evaluate its role in the onset of type 2 diabetes mellitus.

Hematospermia in a Transgender Woman with Evidence for Endometrial Tissue in the Prostate.

Background/Objective: The frequency of hematospermia in transgender women is unknown. This report aimed to describe the development of hematospermia in a transgender woman. Case Report: A 35-year-old transgender woman treated with estradiol valerate and leuprolide presented with painless rust-tinged ejaculate, urethral bleeding after ejaculation, and intermittent hematuria. Her medical history included gastroesophageal reflux disease, internal hemorrhoids, and attention deficit hyperactivity disorder with negative tobacco smoking and urologic history. Additional medications included emtricitabine-tenofovir disoproxil fumarate and fexofenadine. Physical examination did not reveal constitutional or genitourinary abnormalities. Urinalysis and culture disclosed rare white blood cells with gram-variable bacilli. The chlamydia, gonorrhea, and human immunodeficiency virus test results were negative. Abdominal computed tomography did not reveal bladder or prostate cancer, calcifications, inflammation, or cysts. She continued to have symptoms after this initial workup. One year after the initial symptom onset, transrectal ultrasound disclosed a 1.7-cm midline posterior prostatic cyst with hemorrhagic products, later revealed by magnetic resonance imaging as communicating with the left seminal vesicle. Two ultrasound-guided transperineal biopsy samples revealed benign prostatic tissue with a small focus of Müllerian or endometrial-type tissue, evidenced by immunopositivity for paired-box gene 8 and estrogen receptor in epithelium and cluster of differentiation 10 immunopositivity in stroma. After medical consultation, the patient underwent prostatic cyst aspiration, resection of the transurethral ejaculatory ducts, and orchiectomy. She did not experience any complications after these procedures. Discussion: The etiology of hematospermia may be idiopathic, iatrogenic, anatomic, or pathologic. Conclusion: Occult endometriosis or ectopic Müllerian epithelial tissue growth may occur in transgender women taking feminizing gender-affirming hormone therapy.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Bone health in transgender assigned female at birth people: effects of gender-affirming hormone therapy and gonadectomy.

Introduction: Gender-affirming hormone therapy (GAHT) and gender-affirming surgery (GAS) may be desired by transgender and gender-diverse (TGD) individuals who want to affirm their gender identity. Testosterone is the basis of GAHT for transgender individuals assigned female at birth (AFAB), whereas GAS can involve hysterectomy, bilateral salpingectomy, bilateral oophorectomy (BO), thorax masculinization, and phalloplasty. Our study aimed to evaluate the effects of GAHT on the bone health of TGD AFAB individuals who have undergone or not undergone BO. Methods: This was a single-center, longitudinal study with retrospectively collected data. TGD AFAB GAHT-naïve individuals were enrolled and underwent dual-energy X-ray absorptiometry scans and laboratory tests (hormonal and bone metabolism parameters) at baseline and after 5 and 10 years of GAHT. Results: Two hundred and forty-three TGD AFAB people were included in this study. Seventy-five subjects had completed data for 5 years and 19 subjects for 10 years of GAHT. At baseline, low bone density (Z-score < -2.0) was found in 2.5% (6/243) of subjects for lumbar spine (LS), whereas total hip (TH) and femoral neck (FN) Z-scores and laboratory tests were within the normal female range. After stratifying by physical activity, the physically active group showed significantly higher LS BMD and Z-scores (p ≤ 0.05). Five years after the start of GAHT, a significant reduction in LS (p ≤ 0.05), TH (p ≤ 0.001), and FN (p ≤ 0.01) Z-scores was detected. A significant reduction in the Z-scores of all three bone sites was observed only in the subgroup that had undergone BO. After 5 years of GAHT, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.001). Significantly higher estradiol levels were detected in the 5-year no-BO subgroup compared to those in the 5-year BO subgroup (p ≤ 0.001). A significant reduction in LS and TH Z-scores were observed after 10 years of GAHT. At this time, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.01). Conclusion: Bone density in TGD AFAB individuals is comparable to that in their peers prior to GAHT and BO, but those subjects who underwent BO had a reduced Z-score at LS, FN, and TH after 5 years and at LS after 10 years of GAHT.

Resolution of metabolic dysfunction-associated steatohepatitis with estradiol in a transgender female: A case report.

A 16-year-old trans female patient presented to our Gender Health Program for gender-affirming care. Her intake evaluation revealed signs of hepatocellular injury and fibrosis concerning for metabolic dysfunction-associated steatohepatitis (MASH) and she was referred to a Pediatric Hepatologist. Subsequent delays in initiating hormone therapy caused a decline in her mental health, and she began experiencing suicidal ideations. Gender-affirming hormone therapy has been shown to significantly reduce depressive symptoms and suicidal ideations in transgender and gender diverse youth, and studies in animal models suggest improvement in hepatic steatosis in response to estrogen. A multidisciplinary meeting with Gender Health, Psychiatry, and Hepatology appropriately weighed the benefits of life-saving hormone therapy and the possibility of an improvement in her comorbid liver condition with the risk of further liver damage from estrogen therapy. The teams and the patient agreed to start estradiol with subsequent resolution of laboratory and radiographic evidence of MASH.