OBJECTIVES:Two common endocrine manifestations of cystic fibrosis (CF) are cystic fibrosis-related diabetes (CFRD) and cystic fibrosis-related bone disease (CFBD). Trends in CF endocrinopathies in emerging adults during health care transition have not been well studied. Our primary aim was to examine changes in glycemic control in participants with CFRD and bone density in all participants up to 10 years after transition to adult CF care. Secondary aims included analyzing rates of endocrine screening exams. METHODS:This was a retrospective chart review study that included participants ages 18-30 with CF who transitioned to a single center adult CF clinic between January 2013 and June 2023. The final cohort included 94 participants. Bone mineral density based on vitamin D status, CFRD diagnosis and highly effective modulator use was compared using two-sample t-tests, and linear mixed effects analysis was used to analyze hemoglobin A1c over time. RESULTS:Participants with CFRD on insulin demonstrated a mean increase of hemoglobin A1c by a geometric mean of 7.8% (62 mmol/mol) to 9.4% (79 mmol/mol) after 5 years of adult follow up (P = .003). Forty-seven percent of all emerging adults exhibited at least one bone mineral density Z-score < -1. Completion rates of oral glucose tolerance tests and dual-energy x-ray absorptiometry screenings were low. CONCLUSIONS:Health outcome measures of CFRD and CFBD worsen during transition from pediatric to adult CF care at a single CF Care Center. Physicians should recognize this vulnerable period of transition and institute programs to increase screening of CFRD and CFBD during this period.

BACKGROUND:Transgender women (TGW) experience unique hormonal contexts and high HIV incidence, yet the mucosal microbiome among TGW remains understudied. Sex hormones and geography may shape microbial composition, but the relative contributions of gender identity, feminizing hormone therapy (FHT), and location are unclear. METHODS:We conducted a multi-site study of TGW using FHT and cisgender men who have sex with men (MSM), all without HIV, in Atlanta, USA (n = 58; 25 TGW, 33 MSM) and Bangkok, Thailand (n = 147; 97 TGW, 50 MSM)(n = 205). We also conducted longitudinal sampling in 21 TGW pre/post FHT initiation. Rectal swabs were collected from all participants, with optional neovaginal sampling in TGW. Microbiota composition was analyzed using 16S rRNA sequencing, and associations with gender category, geography, and hormone concentrations were assessed using linear decomposition modeling (LDM) and BOUTH analysis. RESULTS:Here we show that the rectal microbiota differ significantly by both gender category and geography. TGW exhibit enrichment of estrogen-metabolizing taxa across sites, while MSM show Prevotellaceae enrichment in Atlanta only. Alpha diversity varies by location but not gender category. Neovaginal microbiota differ markedly from rectal composition, showing enrichment of skin- and gut-associated taxa and anaerobic taxa associated with HIV seroconversion. No significant rectal microbiota shifts are observed after short-term FHT initiation, possibly reflecting subtherapeutic hormone exposure. CONCLUSIONS:These findings underscore the need to consider gender identity as a complex biosocial phenotype in HIV prevention and highlight the potential role of mucosal microbiota in shaping HIV vulnerability in TGW.

BACKGROUND:In individuals with cystic fibrosis (CF), lean mass and muscle strength are important predictors of clinical outcomes. This study evaluated associations among body composition, handgrip strength, muscle quality, physical activity, and health-related quality of life in CF. METHODS:This observational, cross-sectional study included 27 adults with CF and 24 age-matched healthy controls. Body composition was assessed using dual-energy x-ray absorptiometry, physical activity by self-reported questionnaire, strength by handgrip dynamometry, and quality of life by the CF Quality of Life-Revised (CFQ-R) questionnaire. Muscle quality was defined as handgrip strength divided by appendicular lean mass. Analyses included t- tests and Pearson or Spearman correlations. RESULTS:Demographics, body composition, handgrip strength, and muscle quality were similar between those with CF and controls. Among those with CF, muscle quality was positively associated with total physical activity score (r = 0.49, P = 0.009). Handgrip strength was positively associated with lean mass (r = 0.86, P < 0.001) and bone mineral density (r = 0.64, P < 0.001). Regarding CFQ-R, lean mass was positively associated with body image and emotion (r = 0.41, P = 0.03), and body fat was associated with lower physical functioning (r = -0.63, P = 0.004), greater treatment burdens (r = -0.49, P = 0.01), and worse digestive health (r = -0.45, P = 0.02). CONCLUSION:As the CF population ages, these data support continued efforts to promote physical activity and improve body composition for enhanced quality of life while also highlighting the value of integrating accessible measures of muscle function and quality into routine clinical care.

INTRODUCTION:Little is known about anxiety, depression, and post-traumatic stress disorder (PTSD) diagnoses among midlife and older transgender adults (aged 45 years and older). METHODS:This analysis used electronic health record data from the Study of Transition, Outcomes, and Gender, and included transfeminine (TF;n = 3080) and transmasculine (TM;n = 1705) adults aged 45+, along with demographically matched cisgender men (CM) and cisgender women (CW). History of anxiety, depression, and PTSD diagnoses among TF and TM adults and their CM and CW referents was examined. Estimates were calculated overall and stratified by age groups (45-54, 55-64, 65-74, 75+). Analyses were repeated among subgroups (gender-affirming hormone therapy (GAHT) receipt, minoritized ethnoracial status). Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS:aPRs (95% CI) comparing TF to CM were 2.16 (2.08, 2.23) for anxiety, 2.77 (2.66, 2.89) for depression, and 7.11 (6.16, 8.20) for PTSD; corresponding TF versus CW estimates were 1.38 (1.34, 1.42), 1.65 (1.59, 1.71), and 3.27 (2.89, 3.71). Among TM adults, aPRs versus CM were 2.36 (2.26, 2.46) for anxiety, 3.18 (3.02, 3.34) for depression, and 11.12 (9.49, 13.04) for PTSD; corresponding estimates versus CW were 1.49 (1.44, 1.54), 1.80 (1.73, 1.88), and 4.76 (4.20, 5.39). Elevated prevalence was observed across age strata and among those with evidence of GAHT receipt and was more pronounced among individuals from minoritized ethnoracial groups. CONCLUSION:Anxiety, depression, and PTSD prevalence were substantially higher among TF and TM adults than among matched cisgender referents. Mental health disparities were evident across midlife and older adulthood, underscoring the need for interventions and policies that support equitable mental health among transgender adults.

Hidradenitis suppurativa (HS) typically begins in adolescence as painful, recurring lesions that diminish quality of life. Limited data suggest androgen excess is associated with pediatric-onset HS. HS burden remains unclear in transgender youth who may initiate testosterone therapy. This study compared HS prevalence in transgender youth with matched cisgender youth. Electronic health record data was analyzed from the Study of Transition, Outcomes, and Gender, comprised of Kaiser Permanente enrollees in Northern/Southern California, Georgia, and Mid-Atlantic States (2006-2022). Transfeminine (TF) and transmasculine (TM) youth (<18 y) were matched 1:10:10 to cisgender boys (CB) and cisgender girls (CG) on age, race/ethnicity, enrollment year, and region. HS diagnosis required ≥1 encounter ICD code. The study included 5,637 TM, 1,746 TF, and 109,653 matched cisgender youth (mean age 14.7 y). HS prevalence was 0.4%. TM youth had higher prevalence than CB (0.8% v 0.2%, p<.001) but similar to CG (0.6%, p=.82). TF youth had similar prevalence to CB (0.3% v 0.1%) and CG (0.6%). TM youth prescribed testosterone had higher prevalence than CB (1.0% v 0.2%, p<.001) but similar to CG (0.8%).TF youth prescribed estradiol had similar prevalence to CB (0.5% v 0.1%, p=.13) and CG (0.7%, p=1.00). Clinicians should recognize that HS prevalence in transgender youth is comparable to youth of the same sex assigned at birth, regardless of hormone therapy. HS codes may underestimate prevalence.

OBJECTIVE:To summarize current understanding of cystic fibrosis-related bone disease (CFBD), including its pathophysiology, epidemiology, screening recommendations and management in adults, and to highlight knowledge gaps and research priorities in the era of highly effective CFTR modulator therapy. METHODS:A narrative review of the existing literature on CFBD, encompassing the pathophysiology, epidemiologic data, clinical guidelines for screening and fracture risk assessment, and evidence supporting pharmacologic and non-pharmacologic treatments in adults with CFBD. RESULTS:Cystic fibrosis (CF) is a multisystem autosomal recessive disease caused by variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As survival improves with modulator therapy, CFBD has become an increasingly prevalent complication. Its pathogenesis is multifactorial, due to intrinsic CFTR dysfunction in bone compounded by malnutrition, vitamin deficiencies, chronic inflammation, CF-related diabetes, hypogonadism, and exposure to high-risk medications. Up to two-thirds of adults over 45 years have low bone density, conferring a 2-10-fold higher fragility fracture risk. Current guidelines recommend routine dual-energy x-ray absorptiometry, vertebral fracture assessment, and laboratory evaluation, with individualized bone therapy. Nonpharmacologic therapy includes nutritional optimization, physical activity, and modification of risk factors. Pharmacologic management, including use of bisphosphonates, denosumab and anabolic agents, is extrapolated from general osteoporosis data. CONCLUSION:CFBD is a significant and growing complication in adults with CF. Evidence gaps regarding long-term skeletal effects of CFTR modulators and optimal prevention and treatment strategies, underscores the need for prospective data to guide clinical practice.

BACKGROUND:There are known health inequities among people with cystic fibrosis (PwCF) who are part of a marginalized minoritized community. Lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other gender and sexual minority (LGBTQIA+) people experience health inequity and distrust of healthcare systems due to prior and anticipated discrimination and stigma. Little is known about the priorities and needs of LGBTQIA+PwCF. This study sought to identify health priorities and needs of LGBTQIA+PwCF. METHODS:We recruited LGBTQIA+PwCF and providers of CF and LGBTQIA+ care to participate in an online concept mapping study. Participants responded to the brainstorming prompt about the experiences of LGBTQIA+PwCF and subsequently sorted and rated the statements. Multidimensional scaling and hierarchical cluster analysis determined the clusters representing the brainstormed statements. Participants finalized the concept map through focus groups. RESULTS:A total of 39 individuals (22 PwCF; 17 providers) who ranged in age from 17-62 years (mean 36, SD 10.6 years) brainstormed 202 statements that the study team consolidated into 102 statements. Sorting identified key clusters including increased provider education and considerations for reproductive and gender affirming care. The statements with the most agreement referred to dual stress from both LGBTQIA+ identity and navigating CF-related health needs and for CF care teams to better understand and respect the needs of LGBTQIA+PwCF. CONCLUSIONS:This study highlights the unique health needs of LGBTQIA+PwCF and underscores the paucity of current research. Our findings provide insights for directing future research, creating educational interventions, and developing medical spaces for optimal care.

INTRODUCTION We investigated whether Alzheimer's disease and related dementias (ADRD) are more common among transfeminine (TF) adults than among demographically similar cisgender people enrolled in the same health system. METHODS We analyzed electronic health records of 856 TF adults aged 65+ and matched cisgender men (CM) and cisgender women (CW) and compared ADRD prevalence across groups by calculating enrollment-adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS The aOR of ADRD among TF adults were 1.39 (95% CI: 0.99-1.97) relative to CM and 1.29 (95% CI: 0.92-1.82) relative to CW referents. For TF adults with evidence of receiving gender-affirming hormone therapy (GAHT) receipt, the associations were slightly stronger: 1.75 (1.13-2.69) and 1.70 (1.11-2.60). Results restricted to minoritized ethnoracial groups appeared smaller, but imprecise. DISCUSSION These findings suggest that ADRD diagnosis and management may represent a priority in the healthcare of older TF people, particularly those with a history of GAHT.

BACKGROUND:Cystic fibrosis-related diabetes (CFRD) is one of the most common extrapulmonary complications of cystic fibrosis (CF), characterized by abnormal glucose tolerance due primarily to insulin insufficiency. CF-related prediabetes (CFRpD) represents an asymptomatic stage before CFRD onset, requiring routine screening for detection. We aimed to characterize the metabolic profiles underlying abnormal glucose tolerance in people living with CF (pwCF) and identify disrupted pathways associated with CFRD progression. METHODS:Fasting plasma samples from pwCF with normal glucose tolerance (CF-NGT), CFRpD, CFRD, and from healthy, normoglycemic controls without CF were analyzed using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and lipidomics. Annotated metabolites were used for their individual profiles and pathway analysis. RESULTS:Plasma BCAAs, choline, and methionine were lower in CFRD compared to CF-NGT, and leucine, isoleucine, and methionine were also lower in CFRpD after adjusting for sex and CFTR modulator use. In addition, LPCs and the percentage of methionine oxidation (%OxMet) were significantly higher in CFRD. Lean mass and LMI correlated positively with BCAAs and methionine, though only valine was significant after adjusting for sex in pwCF. In agreement with individual metabolites, pathway analysis indicated disruptions in BCAA biosynthesis and one-carbon metabolism in CFRD. CONCLUSION:These findings suggest that impairments in branchedchain amino acid metabolism, redox balance, and one-carbon metabolism are associated with the pathogenesis of CFRD, including lower lean mass in the case of valine. These metabolites should be further tested as potential biomarkers of CF(p)RD and may provide mechanistic insights into CFRD pathogenesis and therapeutic avenues.

Importance:Acne commonly affects transgender individuals prescribed gender-affirming hormone therapy, yet population-level incidence data remain limited. Objective:To compare the incidence of acne and moderate to severe acne in transgender individuals, including those initiating gender-affirming hormone therapy, with matched cisgender individuals. Design, Setting, and Participants:A retrospective matched cohort study of electronic health record data was carried out across 4 Kaiser Permanente health plan regions. Index dates were the earliest documentation of transgender status, ranging from January 2006 to February 2022, with up to 5 years of follow-up. Participants included individuals without baseline acne, transmasculine individuals, and transfeminine individuals matched with cisgender male and female individuals. Analyses were conducted from November 2024 to November 2025. Main Outcomes and Measures:The primary outcome was incident acne (first acne-coded visit after the index date). The secondary outcome was moderate to severe acne (incident acne followed by prescription fill for isotretinoin or 30 or more days of oral antibiotics). Exploratory analyses compared acne care utilization by transgender status. Results:Overall, 280 997 individuals without baseline acne, including 11 234 transmasculine and 9486 transfeminine individuals, were matched to 132 462 cisgender men and 127 815 cisgender women on age, self-reported race and ethnicity (25 340 Asian [9.0%]; 23 234 non-Hispanic Black [8.3%]; 56 876 Hispanic [20.2%]; 153 666 non-Hispanic White [54.7%]; 6989 other [2.5%]), enrollment year, and region. Of these, 12 156 transgender individuals initiated gender-affirming hormone therapy after the index date. The mean (SD) age at index date was 27.7 (10.0) years for transmasculine individuals and 33.2 (13.5) years for transfeminine individuals. Cumulative incidence of acne at 5 years was 15.8% in transmasculine individuals, 3.8% in matched cisgender male individuals, and 10.5% in matched cisgender female individuals and was 6.0% in transfeminine individuals, 2.9% in matched cisgender men, and 8.4% in matched cisgender women. Acne risk in transmasculine individuals was highest in the first year after testosterone initiation (vs matched cisgender male individuals: hazard ratio (HR), 8.29; 95% CI, 7.11-9.68; vs matched cisgender female individuals: HR, 2.63; 95% CI, 2.33-2.97) and remained higher in subsequent years than among cisgender men (HR, 5.29; 95% CI, 4.45-6.28) and cisgender women (HR, 1.69; 95% CI, 1.46-1.96). Acne risk was higher in transfeminine individuals after starting estradiol than cisgender men (HR, 1.56; 95% CI, 1.31-1.84) and lower than cisgender women (HR, 0.53; 95% CI, 0.46-0.62). Moderate to severe acne incidence followed similar patterns. Conclusions and Relevance:This study revealed distinct acne incidence patterns in transgender individuals compared with matched cis male and female cohorts. Clinicians should monitor and treat acne in transmasculine individuals prescribed testosterone per clinical guidelines, particularly during the first year. Clinicians should also recognize that acne may develop in transfeminine individuals after estradiol initiation.

BACKGROUND:Prevalent and incident heart failure (HF) and its comorbidities have not been characterized in transgender and gender-diverse (TGD) populations. This study determines the prevalence and incidence of HF phenotypes by gender identity. METHODS:A retrospective cohort analysis was performed using deidentified administrative claims from the Optum Labs Data Warehouse (2006-2022). TGD adults and a sample of demographically similar cisgender comparators were identified using a validated algorithm, and gender identity was categorized as cisgender man, cisgender woman, transmasculine, transfeminine, or unclassified TGD. Prevalent and incident HF, including systolic, diastolic, and unclassified phenotypes, were assessed using diagnosis codes. Multivariable logistic and Cox regression models adjusted for age and comorbidities evaluated associations between gender identity and HF. RESULTS:In this cohort of 57 471 TGD individuals and 298 213 demographically similar cisgender comparators, 17 898 TGD people (31.1%) were transmasculine, 9652 (16.8%) were transfeminine, and 29 921 (52.1%) had unclassified TGD identity. In adjusted models, transmasculine people experienced less prevalent systolic HF than cisgender men (odds ratio, 0.37 [98.75% CI, 0.17-0.83]) and women (odds ratio, 0.42 [98.75% CI, 0.19-0.92]). Transmasculine people experienced less incident diastolic HF relative to cisgender men (hazard ratio [HR], 0.65 [98.75% CI, 0.51-0.82]) and women (HR, 0.66 [98.75% CI, 0.52-0.83]). Transfeminine people experienced more incident diastolic HF than cisgender men (HR, 1.36 [98.75% CI, 1.05-1.77]) and women (HR, 1.38 [98.75% CI, 1.07-1.79]). CONCLUSIONS:Prevalent systolic HF and incident diastolic HF differed by gender identity after adjustment for age and clinical comorbidities. Further research is needed to identify underrecognized sex- and gender-based HF risk modifiers.

Disclosure: P. Gupta: None. T.B. Karatas: None. V. Tangpricha: None. Introduction/ Background: The Endocrine Society recommends that transgender individuals prescribed estradiol should have periodic measurement of serum prolactin levels due to elevated risk of hyperprolactinemia. While it is known that estradiol increases prolactin levels, the exact incidence and if there is a correlation that exists between serum prolactin and estradiol levels is not known. Specific Aim: The aim of this study was to assess incidence of prolactin elevation and any relationship between serum prolactin with serum estradiol levels in transgender individuals taking estradiol. Materials and Methods: This was a retrospective chart review. Charts were reviewed of transgender individuals receiving estradiol at a single academic medical center. Participants’ information on gender- affirming hormone therapy, use of anti-psychotics and anti- depressants, serum prolactin and estradiol levels and dates of lab draws were recorded. Linear regression analysis was used to measure the association between prolactin level and estradiol level Results: Sixty-seven (67) participants who were prescribed estradiol with at least one documented prolactin were included. A total of 103 serum prolactin and serum estradiol levels drawn at the same time were available to be analyzed. The mean age of the participants was 35.4 years (SD 13.8). The majority of the participants (38/67) were on oral 17 beta estradiol. The majority of the participants (46/67) were not on any anti-psychotics or anti-depressants. Only 6 prolactin levels (5.8%) were elevated > 20 ng/mL in 5 individuals and none were above 100 ng/mL. Only 1 out of these 5 individuals was on antipsychotics and had 2 consecutive prolactin elevations. There was no significant relationship between serum estradiol and serum prolactin levels (R= 0.18, p=0.068) on linear regression analysis. Presentation: Sunday, July 13, 2025

Nearly all males with cystic fibrosis (MwCF) are infertile and, thus, require the use of assisted reproductive technology (ART) to have biologic children. This study aims to describe the fertility and family-building knowledge, experiences, and care utilization of this population and to compare these findings to the general United States (US) population. We conducted an anonymous cross-sectional study of self-reported survey data compared to data from the 2017–2019 US National Survey for Family Growth (NSFG). We recruited MwCF age 15 years and older at seven US cystic fibrosis (CF) centers. A total of 532 MwCF (mean age 35.3 ± 11.6 years) completed the survey. 83