Association between gender-affirming hormone therapy and measures of glucose metabolism: A longitudinal study.

CONTEXT: The long-term effect of gender-affirming hormone therapy (GAHT) on glucose metabolism is an area of priority in transgender health research. OBJECTIVES: To evaluate the relation between GAHT and changes in fasting blood glucose (FG) and glycosylated hemoglobin (HbA1c) in transmasculine (TM) and transfeminine (TF) persons relative to the corresponding temporal changes in presumably cisgender persons (i.e. without any evidence of TGD status). DESIGN: Retrospective cohort study. SETTING: Three large integrated health systems. PARTICIPANTS: 2,425 TF and 2,127 TM persons compared with 33,995 cisgender males (CM) and 38,913 cisgender females (CF) enrolled in the same health plans. OUTCOMES/MEASURES: Temporal changes in FG and HbA1c levels examined using linear mixed models with main results expressed as ratios-of-ratios. RESULTS: The pre- versus post-GAHT ratios-of-ratio (95% confidence interval) estimates adjusted for age, race/ethnicity, study site, and body mass index in the model comparing TF and CM groups were 1.05 (1.01, 1.09) for FG and 1.03 (0.99, 1.06) for HbA1c. By contrast, the corresponding results in the models contrasting TM and cisgender cohort members were in the 0.99-1.00 range. The ratio-of-ratios comparing post-GAHT changes among transgender and cisgender persons were close to the null and without a discernable pattern. CONCLUSION: Though the within-transgender cohort data suggest an increase in the levels of FG and HbA1c following feminizing GAHT initiation, these changes were no longer evident when compared with the corresponding changes in cisgender referents. Based on these results, clinically important effects of GAHT on routine laboratory markers of glucose metabolism appear unlikely.

Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

BACKGROUND: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning. METHODS: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care. During the workshop, we used results and reviewed existing research to establish research priorities and design studies to address identified knowledge gaps. RESULTS: A total of 303 respondents (85 % PwCF, 15 % caregivers) completed the survey. Highly-rated SRH topics were: 1) effects of CF modulator therapy on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health. Twenty-four workshop participants established the need for further research on sex hormones and CF, optimizing SRH care provision, and fertility/ART. CONCLUSION: SRH is an important and emerging area in CF and thoughtful consideration of community perspectives can ensure that future research is relevant and responsive.

Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.

Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) often incur damage to pancreatic tissue due to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered chloride transport on epithelial surfaces and subsequent development of cystic fibrosis-related diabetes (CFRD). Vitamin D deficiency has been associated with the development of CFRD. This was a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study in adults with CF hospitalized for an acute pulmonary exacerbation (APE), known as the Vitamin D for the Immune System in Cystic Fibrosis (DISC) trial (NCT01426256). This was a pre-planned secondary analysis to examine if a high-dose bolus of cholecalciferol (vitamin D3) can mitigate declined glucose tolerance commonly associated with an acute pulmonary exacerbation (APE). Glycemic control was assessed by hemoglobin A1c (HbA1c) and fasting blood glucose levels before and 12 months after the study intervention. Within 72 hours of hospital admission, participants were randomly assigned to a single dose of oral vitamin D3 (250,000 IU) or placebo, and subsequently, received 50,000 IU of vitamin D3 or placebo every other week, beginning at month 3 and ending on month 12. Forty-nine of the 91 participants in the parent study were eligible for the secondary analysis. There were no differences in 12-month changes in HbA1c or fasting blood glucose in participants randomized to vitamin D or placebo. A high-dose bolus of vitamin D3 followed by maintenance vitamin D3 supplementation did not improve glycemic control in patients with CF after an APE.

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.

Lived Experience of Acne and Acne Treatment in Transgender Patients.

Importance: While acne is common in transgender and gender-diverse people and is associated with gender-affirming hormone therapy, little research has examined these factors and their impact in gender minority groups. Objective: To examine the lived experiences of acne and acne treatment in transgender and gender-diverse participants. Design, Setting, and Participants: This mixed-methods analysis was conducted at a multidisciplinary gender center at a public safety-net hospital and endocrinology and dermatology clinics at a tertiary academic center from January 4, 2021, to April 7, 2022, using semistructured interviews and surveys. Participants were transgender or gender-diverse adults who had received gender-affirming hormone therapy. Data analysis was performed from November 11, 2021, to March 31, 2023. Exposure: Current diagnosis of acne. Main Outcomes and Measures: Interviews exploring the experience of acne and acne treatment were audio recorded, transcribed verbatim, coded using minority stress theory and the socioecological model, and analyzed using thematic analysis. Themes were triangulated with survey data on gender, self-reported acne severity, skin-specific quality-of-life impact, and treatment experience. Results: A total of 32 participants were included in the study (mean [range] age, 32 [18-57] years; 17 transgender men, 11 transgender women, and 4 nonbinary participants). Ten participants (31%) self-rated their skin as currently clear or almost clear, 11 (34%) reported mild acne, and 11 (34%) had moderate to severe acne. Participants described experiences of rejection and bullying related to acne and admitted avoiding social interactions in which they anticipated acne-related discrimination, which led to feelings of depression and anxiety. Acne worsened body appearance dissatisfaction. Transgender women reported acne interfering with feminine gender expression. Transgender men often normalized acne development, sometimes viewing acne positively as an early sign of testosterone action. Most participants tried over-the-counter acne treatments and commonly sought acne treatment advice from physicians, peers, online forums, and social media. Barriers to acne treatments included cost, lack of multidisciplinary care, mistrust toward the health care system, and lack of transgender-specific acne care education. Conclusions and Relevance: In this mixed-methods study, transgender and gender-diverse individuals reported experiencing acne-related stigma and facing barriers to acne treatment. Multilevel changes, such as developing strategies to reduce acne stigma, providing transgender-specific acne care education, facilitating multidisciplinary acne care, and expanding transgender-friendly clinical environments, are recommended to reduce the impact of acne in transgender individuals.

Clinician perspectives and practices related to sexual and reproductive care provision for males with cystic fibrosis.

BACKGROUND: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care. METHODS: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care. We compared responses across groups by population served (pediatric vs. adult vs. both pediatric and adult MwCF) using chi square/Fisher's exact tests. RESULTS: A total of 297 clinicians completed the survey (41 % pediatric, 36 % adult, 23 % both; 27 % physicians, 24 % social workers, 11 % nurses, 41 % other). Nearly all (98 %) believed the CF team had a role in SRH care with 75 % believing they should be primarily responsible. Pediatric clinicians were less likely to deem SRH topics important and less likely to report annual discussions compared to adult colleagues (all p<0.05). Pediatric clinicians reported less comfort in their SRH knowledge than adult colleagues (p<0.001) and in their ability to provide SRH care (p<0.05). Common barriers endorsed by respondents included lack of SRH knowledge (75 %) and presence of family/partners in exam room (64 %). A majority rated SRH screening tools (91 %), partnerships with SRH specialists (90 %), clinician training (83 %), and management algorithms (83 %) as potential facilitators. CONCLUSION: Multidisciplinary CF clinicians perceive SRH for MwCF as important but report suboptimal SRH discussions. Pediatric clinicians report significantly less comfort and skill in discussing and managing male SRH. Identified barriers and facilitators should be used to improve SRH care for MwCF.

Dermatologic care of patients with differences of sex development.

Background: Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex. Objective: Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD. Data sources: Published articles including case series and case reports on PubMed. Study selections: Selection was conducted by examining existing literature with a team of multidisciplinary specialists. Methods: Narrative review. Limitations: This article was not conducted as a systematic review. Results: In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common. Conclusion: Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.

Prevalence of Psoriasis and Perceived Association with Hormone Therapy in Transgender Adults.

Purpose: The role of hormone therapy (HT) in the etiology and progression of psoriasis in the transgender population is unclear. Methods: The prevalence of psoriasis in transmasculine (TM) and transfeminine (TF) adults and perceived links between psoriasis and gender-affirming HT is examined using a cross-sectional survey of 696 transgender individuals. Results: Ever diagnosis of psoriasis was reported by 17 TM persons (4.9%; 95% confidence interval [CI]: 2.6-7.2) and 13 TF persons (3.7%; 95% CI: 1.7-5.7). Prevalence of current psoriasis in TM persons was 2.6% (95% CI: 0.9-4.3) and 1.1% (95% CI: 0.03-2.3) among TF persons. Notably, among participants who had ever had psoriasis, 17% perceived a link between their psoriasis and gender-affirming HT. Conclusions: Prevalence of psoriasis among transgender persons resembled estimates in the general population. Potential associations between psoriasis and its severity with gender-affirming HT warrant further longitudinal research.

Total and free 25-hydroxyvitamin D concentrations and risk of urinary incontinence in women participating in Nurses Health Studies I & II.

BACKGROUND: Urgency urinary incontinence (UUI) occurs in >40% of older women. Our objective was to examine the relationship of total and free plasma 25-hydroxyvitamin D (25(OH)D) and UUI to evaluate vitamin D status as a novel target for prevention of UUI. METHODS: We conducted a nested case control study using the Nurses' Health Study (NHS) and NHS II. Using stored plasma samples from 2000, we measured total 25(OH)D, free 25(OH)D, and intact parathyroid hormone (PTH) levels and examined their relationship to incident UUI from 2000 to 2013. Plasma biomarker levels were categorized as quartiles. Multivariable-adjusted odds ratios of UUI were estimated by conditional logistic regression models (with matching by age) across categories of each biomarker and covariates. RESULTS: The analytic sample included 398 cases of incident UUI and 398 matched controls with a mean age of 50 years. We found a strong correlation of plasma levels of total 25(OH)D with free 25(OH)D (r=0.5). Plasma total 25(OH)D and free 25(OH)D concentrations were negatively correlated with PTH (r=-0.08 AND -0.09, respectively). Overall, we found no evidence that levels of total plasma 25(OH)D, free 25(OH)D, or PTH were related to incident UUI after adjustment for obesity, physical activity, cigarette smoking, menopausal status, hypertension, and type 2 diabetes. CONCLUSIONS: Free plasma 25(OH)D by quartile, as well as total plasma 25(OH)D, was not associated with incident UUI in women. We found that plasma total and free 25(OH)D were highly correlated with each other and inversely correlated with PTH. Plasma free 25(OH)D did not provide additional predictive value in determining risk of UUI.

Changes in bone turnover after high-dose vitamin D supplementation during acute pulmonary exacerbation in cystic fibrosis.

In people with cystic fibrosis (CF), chronic inflammation and infection increase the risk for low bone mineral density and CF-related bone disease. During acute pulmonary exacerbations (APE), people with CF have increases in markers of bone resorption. Vitamin D has been proposed as a potential nutrient to lower inflammation. In this ancillary analysis of the Vitamin D for the Immune System in CF study, we hypothesized that vitamin D administered at the time of APE would have favorable changes on bone turnover markers compared to placebo. Participants with CF were randomized to receive a single dose of 250,000 IU of vitamin D or placebo during an APE and followed for 1 year for the primary outcome of APE or death after randomization. Bone turnover markers: C-terminal telopeptide (CTX-1) and procollagen type 1 intact N-terminal propetide (P1NP) were assessed at randomization (during APE) and after recovery from the APE in 45 participants. Participants randomized to vitamin D had significant decreases in markers of bone turnover; participants who received placebo had non-significant increases in markers of bone turnover. Vitamin D supplementation during an APE may help reduce the risk for CF-related bone disease.

Predicting glycemic control status and high blood glucose levels through voice characteristic analysis in patients with cystic fibrosis-related diabetes (CFRD).

Cystic fibrosis-related diabetes (CFRD) is associated with reduced life expectancy in adults with cystic fibrosis (CF). Voice analysis may be a convenient method for diagnosing and monitoring CFRD. This study aims to determine the relationship between voice characteristics and markers of glucose and glycemic control and to identify if voice analysis can predict high blood glucose levels and glycemic control in adults with CFRD. We conducted a prospective cross-sectional study in adults with CF from March to December 2021. We recorded 3-second voice samples of a sustained /a/ vowel and analyzed voice characteristic using the Computerized Speech Lab with the Multi-Dimensional Voice Program. In female participants with CFRD, the noise-to-harmonic ratio was significantly lower in those with HbA1c ≥ 7. Furthermore, fundamental frequency variation was significantly lower in both male and female participants with CFRD who had a glucose level of 200 mg/dL or higher at the time of collection. This finding was also associated with a high level of point-of-care glucose. The human voice has potential as a non-invasive tool for measuring glucose levels and glycemic control status in CFRD patients in the future.

Adherence to Gender Affirming Hormone Therapy in Transgender Adolescents and Adults: A Retrospective Cohort Study.

CONTEXT: Transgender and gender diverse (TGD) individuals often seek gender-affirming hormone therapy (GAHT). While receipt of GAHT has been associated with improved well-being, the risk of GAHT discontinuation and its reasons are not well known. OBJECTIVE: There were two main objectives: (1) To investigate the proportion of TGD individuals who discontinue therapy after an average of 4 years (maximum 19 years) since GAHT initiation; and (2) to explore reasons for GAHT discontinuation. This was a retrospective cohort study at academic centers providing care to TGD adolescents and adults. TGD individuals prescribed estradiol or testosterone between January 1, 2000, and January 1, 2019, were included. GAHT continuation was ascertained using a 2-phase process. In phase 1, Kaplan-Meier survival analyses were used to examine likelihood of GAHT discontinuation and compare discontinuation rates by age and sex assigned at birth. In phase 2, reasons for stopping GAHT were investigated by reviewing records and by contacting study participants who discontinued therapy. The main outcome measures were incidence and determinants of GAHT discontinuation. RESULTS: Among 385 eligible participants, 231 (60%) were assigned male at birth and 154 (40%) were assigned female at birth. Less than one-third of participants (n = 121) initiated GAHT prior to their 18th birthday, constituting the pediatric cohort (mean age 15 years), and the remaining 264 were included in the adult cohort (mean age 32 years). In phase 1, 6 participants (1.6%) discontinued GAHT during follow-up, and of those only 2 discontinued GAHT permanently (phase 2). CONCLUSION: GAHT discontinuation is uncommon when therapy follows Endocrine Society guidelines. Future research should include prospective studies with long-term follow-up of individuals receiving GAHT.

Prevalence of self-inflicted injuries among transgender and gender diverse adolescents and young adults compared to their peers: an examination of interaction with mental health morbidity.

PURPOSE: Compare occurrence of self-inflicted injuries among transgender and gender diverse (TGD) youth to that of their cisgender peers while accounting for mental health diagnoses. METHODS: Review of electronic health records from three integrated health care systems identified 1087 transfeminine and 1431 transmasculine adolescents and young adults. Poisson regression was used to calculate prevalence ratios comparing the proportion of TGD participants with at least one self-inflicted injury (a surrogate for suicide attempt) before index date (first evidence of TGD status) to the corresponding proportions in presumed cisgender male and female referents matched on age, race/ethnicity, and health plan. Interactions between gender identities and mental health diagnoses were assessed on multiplicative and additive scales. RESULTS: TGD adolescents and young adults were more likely to have a self-inflicted injury, various mental health diagnoses, and multiple mental health diagnoses than their cisgender peers. The prevalence of self-inflicted injuries among TGD adolescents and young adults was high even in the absence of mental health diagnoses. Results were consistent with positive additive interaction and negative multiplicative interaction. CONCLUSIONS: Universal suicide prevention efforts for all youth, including those with no mental health diagnoses, and more intensive suicide prevention efforts for TGD adolescents and young adults and those with at least one mental health diagnosis are warranted.

Validation of an administrative algorithm for transgender and gender diverse persons against self-report data in electronic health records.

OBJECTIVE: To adapt and validate an algorithm to ascertain transgender and gender diverse (TGD) patients within electronic health record (EHR) data. METHODS: Using a previously unvalidated algorithm of identifying TGD persons within administrative claims data in a multistep, hierarchical process, we validated this algorithm in an EHR data set with self-reported gender identity. RESULTS: Within an EHR data set of 52 746 adults with self-reported gender identity (gold standard) a previously unvalidated algorithm to identify TGD persons via TGD-related diagnosis and procedure codes, and gender-affirming hormone therapy prescription data had a sensitivity of 87.3% (95% confidence interval [CI] 86.4-88.2), specificity of 98.7% (95% CI 98.6-98.8), positive predictive value (PPV) of 88.7% (95% CI 87.9-89.4), and negative predictive value (NPV) of 98.5% (95% CI 98.4-98.6). The area under the curve (AUC) was 0.930 (95% CI 0.925-0.935). Steps to further categorize patients as presumably TGD men versus women based on prescription data performed well: sensitivity of 97.6%, specificity of 92.7%, PPV of 93.2%, and NPV of 97.4%. The AUC was 0.95 (95% CI 0.94-0.96). CONCLUSIONS: In the absence of self-reported gender identity data, an algorithm to identify TGD patients in administrative data using TGD-related diagnosis and procedure codes, and gender-affirming hormone prescriptions performs well.