Gender-affirming Hormonal Therapy Research Articles

7978 Metabolic Outcomes in Transgender Youth Receiving Affirming Hormonal Therapy

Abstract Disclosure: M. Salama: None. R. Basmaci: None. T. Rajjo: None. O. Chuzhyk: None. A.N. Lteif: None. A. Al Nofal: None. Objective: Heightened societal acceptance of transgender youth and increased awareness of their unmet medical needs have led to a rise in referrals for hormonal therapy. There is limited literature available on the metabolic outcomes of hormone therapy on transgender youth. We investigated how the different metabolic markers of cardiovascular disease change after the initiation of gender-affirming hormonal therapy in transgender adolescents. Methods: A Retrospective, observational cohort study based on chart review of all children with gender dysphoria (under 18 years of age) who were evaluated in the Pediatric Endocrinology Clinic in a tertiary care center between January 2015 and December 2022. Children's demographic information, baseline weight, height, BMI, hematocrit, lipid profile, ALT, prolactin, and HbA1C levels were obtained before and after the initiation of gender-affirming hormonal therapy. The Wilcoxon signed-rank test was employed for paired analysis, while the chi-square test was used as appropriate. Results: We identified 106 transgender youth who were included in the analysis, with a median age at the start of hormonal therapy of 16 years (IQR: 15-17); comprising 68 trans-males (64%) and 38 trans-females (36%). The median treatment duration was 34 months (IQR: 18-54). Among trans-males, ALT levels increased post-treatment (mean difference 6.851 U/L, p < 0.001), as did BMI Z scores (mean difference 0.257, p < 0.001) and LDL-C (mean difference 12.734 mg/dl, p = 0.002), triglycerides (mean difference 10.18 mg/dl, p = 0.009), non-HDL-C (mean difference 12.8 mg/dl, p = 0.002), and total cholesterol (mean difference 10.18 mg/dl, p = 0.02). No significant differences were observed in HbA1C and HDL-C post-treatment. Among transfemales, BMI Z-scores were higher post-treatment (mean difference 0.27, p = 0.007), with increased total cholesterol (mean difference 19.88 mg/dl, p = 0.008), LDL-C (mean difference 12.6 mg/dl, p = 0.02), and HDL-C (mean difference 11.38 mg/dl, p < 0.001). Other variables did not significantly differ pre-and post-treatment. Ten transfemales with measured prolactin levels pre- and post-treatment showed no statistically significant differences. Conclusion: This pilot study revealed increased BMI Z scores following the commencement of hormone therapy in both trans-male and trans-female youths. Moreover, masculinizing treatment led to increased ALT levels. Furthermore, the cardiometabolic profile exhibited diverse alterations, particularly higher LDL-C levels in both cohorts. These findings underscore the necessity for close monitoring of these parameters during the treatment of transgender youth. Larger prospective randomized controlled trials are essential to comprehensively assess the impact of gender-affirming therapy on transgender youth. Presentation: 6/2/2024

The vaginal microbiome of transgender men receiving gender-affirming hormonal therapy in comparison to that of cisgender women

The vaginal microbiome of trans men and menopausal women is suspected to be similar due to a lack of estrogen leading to the absence of lactobacilli. However, data are scarce. We performed an analysis of the vaginal microbiome of trans men (n = 25) in comparison to that of menopausal (n = 25) and premenopausal women (n = 25). The vaginal microbiome of trans men and menopausal women showed a higher alpha diversity than that of premenopausal women. Various beta diversity indices (e.g., Bray‒Curtis (Un-)Weigthed Unifrac), showed significant differences in community composition between trans men and premenopausal (p < 0.001) and menopausal women (p < 0.001). The vaginal microbiome of trans men is characterized by a loss of Lactobacillus and an increase in bacteria associated with the intestinal flora (e.g., Campylobacter, Anaerococcus, Dialister, Prevotella). The abundance of Dialister and Prevotella decreased with the length of hormonal therapy in trans men. The Nugent score, Pap smear and HPV status did not differ between the study groups. The vaginal microbiome of trans men differs from that of premenopausal women but shows similarities to that of menopausal women. The duration of hormonal therapy in trans men may have important impacts on the vaginal microbiome and thus possibly on the risk for STIs.

Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals

BackgroundLimited data exists regarding gender-specific microbial alterations during gender-affirming hormonal therapy (GAHT) in transgender individuals. This study aimed to investigate the nuanced impact of sex steroids on gut microbiota taxonomy and function, addressing this gap. We prospectively analyzed gut metagenome changes associated with 12 weeks of GAHT in trans women and trans men, examining both taxonomic and functional shifts.MethodsThirty-six transgender individuals (17 trans women, 19 trans men) provided pre- and post-GAHT stool samples. Shotgun metagenomic sequencing was used to assess the changes in gut microbiota structure and potential function following GAHT.ResultsWhile alpha and beta diversity remained unchanged during transition, specific species, including Parabacteroides goldsteinii and Escherichia coli, exhibited significant abundance shifts aligned with affirmed gender. Overall functional metagenome analysis showed a statistically significant effect of gender and transition (R2 = 4.1%, P = 0.0115), emphasizing transitions aligned with affirmed gender, particularly in fatty acid-related metabolism.ConclusionsThis study provides compelling evidence of distinct taxonomic and functional profiles in the gut microbiota between trans men and women. GAHT induces androgenization in trans men and feminization in trans women, potentially impacting physiological and health-related outcomes.Trial registrationClinicaltrials.gov NCT02185274.

Sexual Dimorphism in the Musculoskeletal System: Sex Hormones and Beyond.

Mounting evidence indicates that whereas some fundamental aspects of bone cell differentiation and function are similar in females and males, there is a clear contribution of sex/gender on the effects of signaling molecules on bone mass and strength and, consequently, on the effects of pharmacologic approaches to treat skeletal disorders. However, until recently, most studies were designed and performed using only 1 sex, resulting in a scarcity of published information on sexual dimorphism of the musculoskeletal system, including the mandible/masticatory muscles and the axial and appendicular bones and skeletal muscles. Further, it is now recognized that scientific rigor requires the study of both males and females. Therefore, there is an increasing need to understand the molecular and cellular basis for the differential outcomes of genetic manipulations and therapeutic agent administration depending on the sex of the experimental animals. Studies have shown higher muscle mass, cancellous bone mass, and long bone width in males compared with females as well as different traits in the pelvis and the skull, which are usually used for gender identification in forensic anthropology. Yet, most reports focus on the role of sex hormones, in particular, the consequences of estrogen deficiency with menopause in humans and in ovariectomized animal models. In addition, emerging data is starting to unveil the effects of gender-affirming hormonal therapy on the musculoskeletal system. We summarize here the current knowledge on the sex/gender-dependent phenotypic characteristics of the bone and skeletal muscles in humans and rodents, highlighting studies in which side by side comparisons were made.

The Role of Sex and Gender in Transgender Bone and Other Musculoskeletal Health.

Musculoskeletal changes occur with gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS) used in the care of transgender adolescents and adults. Survey results have shown that orthopaedic surgeons desire to care for transgender individuals but express concern over a knowledge deficit. This article reviews the physiology and pathophysiology that may occur with GAHT and GAS. Transgender women have lower bone mineral density (BMD) prior to GAHT than cisgender men. Limited fracture data would suggest that transgender women >50 years of age have fracture rates similar to those of cisgender women. Transgender men have normal BMD prior to GAHT and are not at an increased risk for fracture compared with cisgender women. The use of puberty-blocking medications in the care of transgender youth does result in a decline in BMD, which returns to baseline with GAHT, but the effect of delaying puberty on maximal BMD and the lifetime fracture risk are unknown. At present, dual x-ray absorptiometry (DXA) is used to measure BMD and assess fracture risk. Attention should be paid to using the appropriate reference group in the interpretation of DXA for transgender individuals. Promote musculoskeletal health by ensuring appropriate calcium, vitamin D, weight-bearing activity, and a healthy lifestyle. Adherence to GAHT needs to be encouraged to avoid bone loss. Data with regard to therapy for osteoporosis in transgender patients have been lacking, but, at present, use of available therapies is expected to be effective. Information with regard to differences in other musculoskeletal health issues such as joint injuries has been lacking in transgender individuals.

Early changes in muscle strength and body composition under gender-affirming hormonal therapy in transgender people assigned female at birth

Early changes in muscle strength and body composition under gender-affirming hormonal therapy in transgender people assigned female at birth

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.

Cardiopulmonary Exercise Testing in Transgender and Gender-Diverse Patients: The Influence of Sex and Gender on Predicted Aerobic Capacity

BackgroundSex assigned at birth (SAB) is currently used to calculate predicted normative values for oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) in transgender and gender diverse (TGD) patients. It is unclear if this is physiologically valid once gender-affirming hormonal therapy (GAHT) has been instituted. Research QuestionWhat are the changes in functional aerobic capacity (FAC) and in percentage of predicted (%pred) peak VO2 when gender is used, instead of SAB, to estimated normative predicted values among TGD patients >14 years of age who are receiving GAHT? Study Design and MethodsWe retrospectively analyzed 16 referred TGD patients (8 transgender men, 8 transgender women) receiving GAHT therapy at the time of the test. Data collected and analyzed included: clinical indication for CPET, biometrics (age, height, and weight), CPET parameters (treadmill, Mayo Clinic protocol, without chest binder), chest imaging, echocardiographic results, and hemoglobin levels. ResultsIn transgender women, the use of gender congruent normative predictive values, instead of SAB, significantly increased FAC (69.70 ± 4.35 vs. 87.82 ± 5.15 [%]; mean ± SE; for SAB and gender, respectively; p= <0.0001) and %pred peak VO2 (66.53 ± 4.17 vs. 89.69 ± 5.60 [%]; mean ± SE; for SAB and gender, respectively; p= <0.0001). In transgender men, the use of gender congruent normative predictive values showed that both FAC and %pred peak VO2 significantly decreased (approximately 20% and 25%, respectively). Deconditioning was the most frequent CPET finding among transgender men. InterpretationAmong TGD individuals receiving GAHT, the use of gender to calculate normative values affects %pred peak exercise VO2 and FAC significantly. Body composition changes after GAHT require regular monitoring of muscle strength, lean body mass, and aerobic capacity. Cardiopulmonary symptoms among TGD patients should be assessed with these variables in mind –especially in the presence of chronic cardiac and pulmonary diseases.

Breast care considerations for transgender and gender-diverse patients.

Transgender and gender-diverse (TGD) persons represent a small but growing population in the United States. Accessing inclusive, equitable, and evidence-based healthcare remains a challenge for this patient population. Many TGD persons seek gender-affirming care, including gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS), to help ameliorate the physical and mental aspects of their gender incongruence. Both GAHT and GAS induce clinically important histopathologic and anatomic changes in breast tissue. Consequently, breast care in TGD persons has become an increasingly recognized topic of importance in gender-affirming care. However, there remains a scarce but growing base of literature specifically addressing the unique healthcare needs of breast care in TGD patients. This article will review how to establish trusting patient-provider relationships for TGD patients, gender inclusivity in breast clinics and imaging centers, the influence of GAHT and GAS on breast tissue, breast cancer screening recommendations and barriers, and breast cancer risk and treatment considerations in TGD persons.

Exploring Hormone Therapy Effects on Reproduction and Health in Transgender Individuals.

Transgender individuals often face elevated mental health challenges due to gender dysphoria, but gender-affirming treatments such as surgery and hormone therapy have been linked to significant improvements in mental well-being. The potential influence of time and circadian rhythms on these treatments is prevalent. The intricate interplay between hormones, clock genes, and fertility is profound, acknowledging the complexity of reproductive health in transgender individuals. Furthermore, risks associated with gender-affirming hormonal therapy and potential complications of puberty suppression emphasize the importance of ongoing surveillance for these patients and the need of fertility preservation and family-building options for transgender individuals. This narrative review delves into the intricate landscape of hormone therapy for transgender individuals, shedding light on its impact on bone, cardiovascular, and overall health. It explores how hormone therapy affects bone maintenance and cardiovascular risk factors, outlining the complex interplay of testosterone and estrogen. It also underscores the necessity for further research, especially regarding the long-term effects of transgender hormones. This project emphasizes the critical role of healthcare providers, particularly obstetricians and gynecologists, in providing affirming care, calling for comprehensive understanding and integration of transgender treatments. This review will contribute to a better understanding of the impact of hormone therapy on reproductive health and overall well-being in transgender individuals. It will provide valuable insights for healthcare providers, policymakers, and transgender individuals themselves, informing decision-making regarding hormone therapy and fertility preservation options. Additionally, by identifying research gaps, this review will guide future studies to address the evolving healthcare needs of transgender individuals. This project represents a critical step toward addressing the complex healthcare needs of this population. By synthesizing existing knowledge and highlighting areas for further investigation, this review aims to improve the quality of care and support provided to transgender individuals, ultimately enhancing their reproductive health and overall well-being.

Access to gender-affirming hormonal therapy in Russia: perspectives of trans people and endocrinologists

Purpose Worldwide, trans people are known to take hormones without prescription or take higher or lower doses than prescribed. The study’s goal was examination of the social context behind provision and receiving of gender-affirming hormonal therapy (GAHT) in Russia, as well as collection of opinions on the organization of healthcare. Methods Semi-structured interviews with 20 trans individuals and 6 endocrinologists. Results Trans respondents started GAHT between 2004 and 2022. Over that period, the number of trans-competent endocrinologists increased and it became easier to receive the diagnosis F64.0 “transsexualism” (ICD-10), which qualifies one to obtain GAHT. However, the majority still took hormones without supervision. The reasons for self-medication included: the lack of the diagnosis, high cost of appointments and tests, age under 18, and self-perceived understanding of principles of GAHT. Most endocrinologists learnt about GAHT after being approached by a trans patient. They received information from advanced training courses and academic literature. The specialists had diverse opinions on the ideal policy of providing GAHT to trans people, but all claimed that in Russian political realities they found the diagnosis “transsexualism” a necessary prerequisite for initiating GAHT to safeguard both doctors and patients. Conclusions The lack of strict law enforcement in the pharmacological sphere in Russia enabled many trans people to initiate GAHT without supervision. Trans-competent endocrinologists were available for those who needed them. Under current political circumstances it is unlikely that the informed consent model (prescription without a psychiatric diagnosis) can be implemented in Russia.

OR31-03 Testosterone Gender-affirming Hormonal Therapy Is Associated With Decreased Cerebral Blood Flow In Transgender Teens

Abstract Disclosure: S. Cote: None. K. Fathy: None. S. Lenet: None. O. Espinosa-Bentancourt: None. E. Lavallee: None. E. Croteau: None. D. Rottembourg: None. J. Lepage: None. K. Whittingstall: None. There is increasing demand for gender-affirming hormonal therapy (GAHT) in recent years, with increased access to GAHT for transgender teenagers. While it is well documented that psychological outcomes and quality of life improve after GAHT, it remains unclear how cerebrovascular physiology changes with GAHT. Therefore, this study aimed to investigate the effects of testosterone GAHT on cerebral microvascular and macrovascular physiology in teenage transgender men receiving GAHT. Six teenage transgender men were referred by their endocrinologist prior to the start of GAHT. Participants visited the research center before GAHT (session 1) and between 3 to 9 months into their GHAT (session 2). At each visit, participants completed a non-contrast-enhanced magnetic resonance imaging (MRI) protocol. This protocol assessed the macrovasculature using time-of-flight magnetic resonance angiography to visualize cerebral arteries and estimate diameters of the Circle of Willis and 2D-Phase Contrast to estimate large artery blood velocity. The microvasculature was assessed using pseudo-Continuous Arterial Spin Labelling, which estimates cerebral blood flow (CBF). Paired-sample t-tests were performed between sessions to determine if arterial diameters, CBF and blood velocity change with GAHT. Whole-brain CBF significantly decreased with GAHT between session 1 and session 2 (CBFS1=69.15 +/- 5.85 ml/100g/min; CBFS2=59.30 +/- 8.11 ml/100g/min; t=3.19, p=0.02, df=5). The average percent change in CBF was -9.85%, and the largest decrease experienced by a participant was -20.44%. Note that even though CBF decreased, average whole-brain CBF for all participants remained in a healthy range. We observed no significant change in large artery blood velocity or arterial lumen diameters of the Circle of Willis after starting GAHT. Our results suggest that GAHT influences the brain’s microvasculature. As women tend to have higher CBF than men, the reduction in CBF likely reflects a masculinization of the brain with GAHT. Without EEG to probe neuronal activity, it is difficult to determine if the change is due to decreased neuronal activity or a structural and/or functional change in the microvasculature. Considering that little is known about the long-term effects of GAHT on the brain, these results highlight the need to better understand how hormonal states impact human cerebrovascular physiology and how it may relate to risk for cerebrovascular disease and neurological disorders. Presentation: Sunday, June 18, 2023

SAT420 Bone Health In Transgender People

Abstract Disclosure: G. Grande: None. C. Ceolin: None. B. Vescovi: None. M. Dall’Agnol: None. C. Ziliotto: None. S. Pasqualini: None. G. Petre: None. A. Scala: None. S. Giannini: None. V. Camozzi: None. A. Bertocco: None. G. Sergi: None. A. Ferlin: None. A. Garolla: None. In transgender subjects, worse Bone Mineral Density (BMD) values were observed when compared to cisgender controls before initiating Gender-Affirming Hormonal Therapy (GAHT). The reasons have not yet been fully clarified. In this study we analyzed bone metabolism and body composition in a population of transgender people before initiating GAHT, and their possible correlation with endocrine profile, mental health, and lifestyle habits. Medical data, phosphocalcic metabolism and hormonal parameters, lumbar and femoral bone mineral density, body composition, strength and psychological well-being (by Patient Health Questionnaire-9-PHQ-9 and Perceived Stress Scale-PSS questionnaires), were collected in a sample of 32 transgender people before GAHT initiation and 32 cisgender controls. Assigned Female At Birth (AFAB) transgender people presented worse Z-score values at total hip and neck femoral sites (-0.52±0.94 vs 0.15±0.82, and -0.37±0.79 vs 0.19±0.66, p=0.04 respectively), while in Assigned Male At Birth (AMAB) transgender people also lumbar sites were compromised in comparison to cisgender controls. No significant difference in phospho-calcium metabolism (calcium, phosphate, PTH and vitamin D) or hormonal profile (Testosterone, estradiol, LH, FSH) was found between the transgender and the cisgender group. PHQ-9 (a questionnaire to screen for depression) scores were higher in the transgender population than cisgender controls (9.35±7.41 vs 4.08±3.14, p=0.03 in AFAB and 9.54±5.45 vs 4.46±3.59, p=0.02 in AMAB transgender people). Multiple regression analysis identified PSS (a tool to assess stress levels and identify which situations are perceived as stressful) score as an independent predictor of total femur BMD, explaining about 54% of the variance. Transgender people before GAHT have worse bone health than cisgender subjects. In particular, BMD was reduced at the hip and in AMAB even at lumbar site. The reduction in bone mass before GAHT seems independent by hormonal and phospho-calcic profile and associated mostly with psychological status. Further study will clarify the specific pathogenetic mechanisms involved in bone growth in transgender people. However, according to our evidences, the psychological stress might influence negatively lifestyle habits therefore being involved in reduced bone health. Early lifestyle and psychological interventions might so be beneficial also for bone health in the transgender population. Presentation: Saturday, June 17, 2023

SAT406 Evaluation Of The Emotional And Cognitive Effects Of Hormone Therapy In Transgender Men And Women

Abstract Disclosure: I. Yaish: None. G. Keltch: None. Y. Greenman: None. K.M. Tordjman: None. Background:- Sex hormones have far-reaching effects on the brain, both emotionally and cognitively. - Varying levels of sex hormones are associated with altered emotional states and cognitive abilities. -No longitudinal study has assessed the impact of cross-sex hormone on these issues in young transgender people. Aim:•To prospectively evaluate the effect of gender-affirming hormonal therapy (GAHT) on cognition and emotional state in transgender men and women initiating therapy Subjects and Methods:- Transgender men (TM) aged 24.6±7.8 y (18-37), and 11 transgender women (TW) 27.3±9.4 (19-46).- Mood questionnaires (PHQ9 and GAD-7), and cognitive tests (short-term logical memory test, sub-tests of knowledge, forward and backward digit recall, number-coding and random learning from WAIS-III, a verbal fluency test and CTMT test) were administered prior to GAHT, and 3-6 months into treatment. - Scores were calculated for emotional stress, memory, attention, and executive functions. - Wilcoxon tests for paired samples assessed the impact of GAHT on these variables. Results - In TM, GAHT significantly improved executive functions but had no effect on memory, attention, and emotional stress. - In TW, GAHT significantly improved memory but had no effect on attention, executive functions, and emotional stress. - Despite a trend for improved emotional stress with GAHT in both groups, over this short study period, this was not significant. Conclusions:- - In keeping with the literature, this short preliminary study showed that estrogen contributes to memory, and testosterone to executive functions.-- This is the first time this has been shown in transgender individuals. -The lack of effect on emotional stress is probably due to the small sample size and short duration, larger studies should elucidate this point. Presentation: Saturday, June 17, 2023

FRI323 Prolactinoma Recurrence With Testosterone Treatment In Transgender Male

Abstract Disclosure: N. Arnouk: None. P.R. Schroeder: None. Introduction: We present a case of recurrent hyperprolactinemia due to testosterone treatment for gender-affirming hormonal therapy in a transgender male after being controlled on cabergoline for more than a year. Case: A 27-year-old female with history of HTN and polycystic ovary syndrome was diagnosed with pituitary microadenoma after hospital admission for headache and blurry vision. MRI brain showed a mass in the sella and right parasella measuring 36 mm W x 36 mm D x 44 mm H. Hormonal workup showed prolactin (PRL) &amp;gt;999 ng/mL in the diluted assay. The patient was treated medically with cabergoline and discharged home. PRL level improved to 22 ng/mL on treatment. Cabergoline was continued at 0.5 mg twice weekly. The patient was lost to follow-up but returned to clinic after 8 months with PRL level of 58 ng/mL. Cabergoline 0.5 mg twice weekly was continued. PRL level monitoring every ∼6 weeks showed an increase to 184 ng/mL and then 199 ng/mL. Cabergoline was increased to 1 mg twice weekly. PRL level 1 month later was 222 ng/mL. Repeat brain MRI showed markedly decreased microadenoma 4.8 X 2.6 mm. The patient was asymptomatic with no headache, blurry vision, or galactorrhea. On further questioning, the patient reported starting transgender female to male testosterone cypionate 200 mg/mL once weekly for the past 6 months. After discussion with the primary care provider who was managing testosterone treatment, he was started on 60 mg weekly, and the dose was gradually increased to 80 mg weekly to stop the menstrual period. With the 60-mg weekly cypionate dose, the testosterone level was 346 pg/mL, and PRL level was 184 ng/mL. With the cypionate dose of 80 mg weekly, PRL increased to 194 ng/mL and 222 ng/mL. The cypionate dose was decreased to 60 mg weekly, based on literature noting elevated PRL level with testosterone replacement in patients with prolactinoma and hypogonadism. Based on repeat blood work showing elevated testosterone 366 pg/mL with PRL 318 ng/mL, the plan is to start an aromatase inhibitor. Discussion: Testosterone treatment as hormonal affirming therapy in some transgender female to male patients may exacerbate pre-existing hyperprolactinemia or induce PRL secretion, thus close monitoring is required. Testosterone is aromatized to estradiol, which then stimulates the release of PRL from the pituitary gland. The serial measurement of estradiol may serve as an index of aromatization. Hyperprolactinemia in this setting is resistant to dopamine agonist therapy, as noted in multiple case reports. There are no established reference ranges for PRL levels for transgender patients on gender-affirming hormone therapy and no current guidelines regarding routine imaging or biochemical assessment during follow-up. Transgender patients with prolactinoma may require additional treatment with non-aromatizable androgens or the concomitant administration of aromatase inhibitors. Presentation: Friday, June 16, 2023

Prevalence of and factors associated with the use of gender-affirming hormonal therapy outside the reference regimen among transgender people in a community-led clinic in Metro Manila, Philippines: a retrospective cross-sectional study

ObjectivesWe aimed to describe the gender-affirming hormonal therapy (GAHT) intake behaviour and regimen and the factors associated with the use of hormones inconsistent with reference GAHT regimen among transgender people...

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

PurposePreliminary 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).MethodsMedical 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).Results14.3% 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.ConclusionsBody composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

IS THERE A DOSE OF CYPROTERONE ACETATE LOW ENOUGH TO AVOID HYPERTENSION DEVELOPMENT IN YOUNG TRANSGENDER WOMEN?

Objective: Cyproterone acetate (CPA) is a progestagen receptor agonist and androgen receptor antagonist widely used in gender-affirming hormonal therapy (GAHT) for transgender women. It is devoid of the mineralocorticoid blocking effect of native progesterone, thus its combination with oestradiol may elicit hydrosaline retention and hypertension. In a retrospective analysis we have found that using CPA for 5 years in young transgender women increases very significantly their SBP and their incidence of hypertension. Due to risks such as meningioma and liver toxicity, the European Medicines Agency (EMA) recommends avoiding doses &gt;10 mg/day if possible; however, present guidelines for GAHT recommend doses up to 100 mg/day. While lower doses may be effective and safer, the dose-dependence for hypertension development with CPA has not been studied. We undertook to study the association between the cumulative dose of CPA in young transgender women and their incidence of hypertension. Design and method: Retrospective review of the clinical records of female transgender people &lt;30-years-old treated with oestradiol + CPA for 5 years. All subjects gave informed consent. They were stratified by quartiles of cumulative CPA intake. We were unable to use doses &lt; 25 mg/day, as only 50 mg pills are available. Results: Data were obtained from 56 subjects. The global adjusted annualized incidence of hypertension 4.96% vs. 0.98% in the reference population (transgender women treated with oestradiol without antiandrogen). By quartiles the incidences were 2.52%/4.13%/5.76%/7.31%, p &lt;0.001 (Figure 1A). Their global adjusted SBP increase was 14 vs. 3 mmHg; by quartiles 7/11/16/22 mmHg, p &lt;0.001 (Figure 1B). Conclusions: We found a clear dose-dependence for the incidence of hypertension associated with CPA in young transgender women, but even the lowest doses we were able to manage did significantly increase the risk. We cannot however rule out that doses as low as 10 mg/day may be effective and safer. We believe that the present recommendations of high CPA doses for GAHT should be reconsidered.

Post-pubertal testosterone implants in female rats, a model of gender-affirming hormonal therapy, induce hypertension that is exaggerated with aging

Introduction: Early pre-pubertal exposure to androgens induces an increase in blood pressure (BP) and renal injury in females, as seen in polycystic ovary syndrome females. However, it is not clear whether treatment with gender-affirming hormonal therapy (GAHT) in trans-men have an impact on their BP and renal health as adults and with aging. Therefore, the present study was undertaken to test the hypothesis that chronic androgen supplements (starting post-pubertal, model of GAHT) in female-to-male trans-sex rats will increase BP and promote renal injury that are exaggerated with aging. Methods: Female SD rats were implanted with testosterone propionate-filled silastic implants (TP, 7.5 mg/10 mm silastic tube/rat, replaced every 3 wks) starting at 7 wks of age (post-pubertal) until 17 months (mos) of age and compared to controls (CON, empty silastic implants). Serum testosterone was measured by LC/MS at 3 mos of age (n=4/grp). Radiotelemetry transmitters were implanted and mean arterial pressure (MAP) was measured at 3 and 17 mos of age (n=3-6/grp). Body composition was determined at 3 and 17 mos of age (n=3-4/grp). Proteinuria was determined at 3, 5 and 7 mos of age (n=4/grp). Serum and urinary creatinine (Cr) were measured at 7 mos of age and Cr clearance was calculated (n=4/grp). Urinary kidney injury molecule-1 (Kim-1) was measured at 12 mos of age (n=3-4/grp). Results: TP had significantly higher serum testosterone compared to CON (6.4 ± 1.5 vs 0.2 ± 0.05 ng/ml; p&lt;0.05). Despite the similar fat mass, lean mass was significantly higher in TP compared to CON starting at 3 mos of age (253.9 ± 6.7 vs 217.7 ± 5.8 g; p&lt;0.05), until 17 mos of age (325.7 ± 15.1 vs 253.5 ± 3.9 g; p&lt;0.05). Proteinuria was significantly higher in TP compared to CON at 5 and 7 mos of age (7.6 ± 1.1 vs 2.4 ± 0.5 mg/24 h and 10.1 ± 1.6 vs 2.4 ± 0.4 mg/24 h, respectively, p&lt;0.05). Cr clearance was significantly lower (0.24 ± 0.03 vs 0.32 ± 0.02 ml/min/100 g, p&lt;0.05) and urinary Kim-1 was significantly higher (6.3 ± 1.5 vs 3.5 ± 0.2 ng/24 h, p&lt;0.05) in TP compared to CON. Importantly, MAP was significantly higher in TP compared to CON starting at 3 mos of age (112 ± 3 vs 106 ± 4 mmHg, p&lt;0.05), with further increases at 17 mos of age (133 ± 1 vs 117 ± 6 mmHg, p&lt;0.05). Conclusion: Post-pubertal testosterone in female sex promotes renal injury and increases BP, independent of adiposity. Aging promotes further increases in BP, suggesting increased risk of cardiovascular diseases. Future studies should determine the mechanisms behind the increase in BP in the female-to-male trans-sex model. P20GM121334, AHA Career Development Award 938320, P20GM104357, R01HL135089, P01HL051971 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Case Series of Ischemic Stroke occurring in Male- to- Female Transgender population on Gender - Affirming Hormonal Therapy and Review of the Literature (P2-5.022)

<h3>Objective:</h3> To stress the importance of individualized vascular risk assessment and shared decision-making to continue Gender-Affirming Hormonal therapy (GAHT) in the Male to Female (MTF) transgender population following ischemic stroke with review of the literature. <h3>Background:</h3> Transgender individuals have higher mental health burden and suicide rates. GAHT is the standard of care for transgender individuals suffering from symptoms of gender dysphoria. Estrogen therapy has been associated with increased stroke risk, but its specific contribution is poorly characterized and appears to be impacted by the route of administration. <h3>Design/Methods:</h3> We include three self-identified MTF transgender patients who had taken GAHT and treated for ischemic stroke inpatient or were seen for stroke follow-up. Data was gathered from chart review including demographics, vascular risk factors, type of GAHT, clinical course, and outcomes. <h3>Results:</h3> Two MTF transgender patients on GAHT were treated inpatient for an acute stroke and one was seen in follow up. At the time of infarct, one MTF transgender patient was on combination hormonal therapy, one patient was on combination hormonal therapy and spironolactone, and one patient was on estrogen hormonal therapy of unknown type. Traditional vascular risk factors were present in the patient population prior to ischemic stroke including: hypertension, hyperlipidemia, type 2 diabetes mellitus, morbid obesity, prior ischemic stroke, tobacco use disorder, alcohol use disorder. <h3>Conclusions:</h3> Each patient in our small series had traditional vascular risk factors in addition to GAHT use prior to ischemic infarct. Identifying and treating comorbid vascular risk factors in MTF transgender patients prior to and during GAHT is essential to decrease ischemic stroke risk. Additional studies are needed to determine the relative impact of GAHT on stroke risk. Given mental health burden of gender dysphoria symptoms, shared decision-making is necessary to determine risks and benefits of continuing GAHT after ischemic stroke in MTF transgender patients. <b>Disclosure:</b> Ms. Giovannini has nothing to disclose. An immediate family member of Dr. Ivan has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Cellular and Molecular Medicine. An immediate family member of Dr. Ivan has received intellectual property interests from a discovery or technology relating to health care. Dr. Karel has nothing to disclose.