Longitudinal metabolic study of red blood cells from patients undergoing gender-affirming testosterone therapy.
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ABSTRACT:
SUBMITTER: Roy MK
PROVIDER: S-EPMC10424140 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Longitudinal metabolic study of red blood cells from patients undergoing gender-affirming testosterone therapy.
Roy Micaela Kalani MK Wilkerson Rebecca Burgoyne RB Alexander Keisha K Nokoff Natalie J NJ Cree-Green Melanie M D'Alessandro Angelo A
Blood advances 20230801 16
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Project description:Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID1, similar to observations in other infections2. Females respond more strongly to vaccines, and adverse reactions are more frequent3, like most autoimmune diseases4. Immunological sex differences stem from genetic, hormonal and behavioural factors5 but their relative importance is only partially understood6-8. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.
| S-EPMC11374716 | biostudies-literature
Project description:BackgroundDNA methylation is an epigenetic mark that is influenced by underlying genetic profile, environment, and ageing. In addition to X-linked DNA methylation, sex-specific methylation patterns are widespread across autosomal chromosomes and can be present from birth or arise over time. In individuals where gender identity and sex assigned at birth are markedly incongruent, as in the case of transgender people, feminization or masculinization may be sought through gender-affirming hormone therapy (GAHT). GAHT is a cornerstone of transgender care, yet no studies to date have investigated its effect on genome-wide methylation. We profiled genome-wide DNA methylation in blood of transgender women (n = 13) and transgender men (n = 13) before and during GAHT (6 months and 12 months into feminizing or masculinizing hormone therapy).ResultsWe identified several thousand differentially methylated CpG sites (DMPs) (Δβ ≥ 0.02, unadjusted p value < 0.05) and several differentially methylated regions (DMRs) in both people undergoing feminizing and masculinizing GAHT, the vast majority of which were progressive changes over time. X chromosome and sex-specific autosomal DNA methylation patterns established in early development are largely refractory to change in association with GAHT, with only 3% affected (Δβ ≥ 0.02, unadjusted p value < 0.05). The small number of sex-specific DMPs that were affected by GAHT were those that become sex-specific during the lifetime, known as sex-and-age DMPs, including DMRs in PRR4 and VMP1 genes. The GAHT-induced changes at these sex-associated probes consistently demonstrated a shift towards the methylation signature of the GAHT-naïve opposite sex, and we observed enrichment of previously reported adolescence-associated methylation changes.ConclusionWe provide evidence for GAHT inducing a unique blood methylation signature in transgender people. This study advances our understanding of the complex interplay between sex hormones, sex chromosomes, and DNA methylation in the context of immunity. We highlight the need to broaden the field of 'sex-specific' immunity beyond cisgender males and cisgender females, as transgender people on GAHT exhibit a unique molecular profile.
| S-EPMC8851870 | biostudies-literature
Project description:Erythrocytosis is a well-recognized consequence of exogenous testosterone, however its prevalence and contributions to thrombosis remain unknown in the context of gender-affirming hormonal therapy. We undertook a retrospective study of transgender and non-binary (TGNB) adults receiving exogenous testosterone. In the retrospective sample, 923 transgender individuals receiving testosterone were identified with 519 having documented pre- and post-testosterone hemoglobin and hematocrit (Hgb/Hct). The mean peak Hgb/Hct was 15.7 g/dL, and 47.0%. Mean time-to-peak Hgb/Hct was 31.2 months; 7.8% developed a hemoglobin >17.5 g/dL, whereas 20% developed a hematocrit of >50%. Testosterone dose reduction occurred in 42% of patients with erythrocytosis and 4.8% underwent phlebotomy. Thromboembolic events occurred in 0.9%, of which 80% had developed erythrocytosis by either Hgb or Hct, including two cases each of superficial and calf vein thrombosis as well as one ischemic stroke. We then performed an analysis of 14,294,784 hospitalizations from the 2016-17 US National Inpatient Sample (NIS), which identified 4141 admissions involving transgender individuals. Of those, seven had erythrocytosis with one concurrent venous thromboembolic event. Hematocrit >50% occurs in up to 20% of transgender individuals receiving testosterone. Despite the high incidence of erythrocytosis, thromboembolic events and hospitalizations involving erythrocytosis were uncommon.
| S-EPMC9009187 | biostudies-literature
Project description:BackgroundThe effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health.AimWe sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation.MethodsThe data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs).OutcomesChanges in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents.ResultsAmong TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity.Clinical implicationsTM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels.Strength and limitationsThe strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration.ConclusionThe influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.
| S-EPMC8444147 | biostudies-literature
Project description:In individuals where gender identity and sex assigned at birth are markedly and consistently incongruent, as in the case of transgender people, feminisation or masculinisation may be sought through gender affirming hormone therapy (GAHT). In this study we profiled genome-wide DNA methylation in transgender women and transgender men, before and during GAHT (6 months and 12 months into hormone treatment).
2022-02-17 | GSE176394 | GEO
Project description:ImportanceGender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research.ObjectiveTo explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans.Design, setting, and participantsThis retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents.ExposureGender-affirming hormone treatment.Main outcomes and measuresMetabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model.ResultsThe cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77).Conclusions and relevanceIn this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.
| S-EPMC11220566 | biostudies-literature
Project description:BackgroundTransgender individuals have long experienced discrimination and exclusion from medicine. Misgendering occurs when an individual is referred to using a gender or address incongruent with their identity. We evaluated the incidence of misgendering throughout the perioperative experience for patients undergoing gender-affirming surgery (GAS).MethodsPatients diagnosed with gender dysphoria who previously received GAS by the senior author were contacted to complete an IRB-approved survey to evaluate instances of misgendering while in the hospital for GAS. Study results were summarized using descriptive statistics.ResultsOf 471 patients contacted, 182 completed the survey (38.6%). The most cited gender identity was transfemale (28.0%). Most patients reported respect for their gender identity (60.4%) and name (76.8%) during their perioperative experience. Twenty-two percent cited triggering experiences, and 15.4% reported interactions with healthcare employees causing them to reach out to a support system. Misgendering most commonly included incorrect use of patients' preferred names and/or pronouns (n = 50, 86.2%), most commonly at surgical check-in (n = 10, 45.5%). Recommendations to improve feelings of gender congruence during patients' stay included updated names and gender identities in electronic medical records (80.8%), and names and pronouns listed on curtains and doors (52.3%) and name tags (51.5%).ConclusionsUntil now, the exact incidence of misgendering among patients seeking GAS have not been well established. Despite high levels of satisfaction, a large proportion still reported serious instances of misgendering. Improvements must be made to the perioperative experience to reduce misgendering and provide support and comfort during the sensitive period surrounding patients' gender transition.Level of evidence: Not gradable.Supplementary informationThe online version contains supplementary material available at 10.1007/s00238-022-02040-2.
| S-EPMC9873212 | biostudies-literature
Project description: Not available
| S-EPMC10167862 | biostudies-literature
Project description:BackgroundTransgender and gender diverse (TGD) persons considering gender affirming therapy have to make many complex medical decisions, potentially without understanding the associated harms or benefits of hormonal and surgical interventions. Further, clinicians are often unaware of how best to communicate information to persons seeking gender affirming therapy. Patient decision aids have been developed to provide evidence-based information as a way to help people make decisions in collaboration with their clinicians. It is unclear whether such tools exist for persons seeking gender affirming therapy. The objective of our systematic review is to search for and determine the quality of any existing patient decision aids developed for TGD persons considering gender affirming therapy, and the outcomes associated with their use.MethodsWe adapted a search strategy for databases using two key concepts "decision support intervention/patient decision aid" and "transgender". We also conducted a brief online search of Google and abstracts from relevant conferences to identify any tools not published in the academic literature. Following study selection and data extraction, we used the International Patient Decision Aid Standards instrument (IPDASi) to assess the quality of patient decision aids, and the Standards for UNiversal reporting of patient Decision Aid Evaluations (SUNDAE) checklist to assess the quality of evaluations.ResultsWe identified 762 studies; none were identified from Google or conference content. One tool met our inclusion criteria: an online, pre-encounter patient decision aid for transmasculine genital gender-affirming surgery developed in Amsterdam, translated in English and Dutch. The tool met all the IPDASi qualifying criteria, and scored a 17/28 on the certification criteria, and 57/112 on the quality criteria. The efficacy of the patient decision aid has not been evaluated.ConclusionsDespite multiple decisions required for gender affirming therapies, only one patient decision aid has been developed for transmasculine genital reconstruction. Further research is required to develop patient decision aids for the multiple decision points along the gender affirming journey.
| S-EPMC8261453 | biostudies-literature
Project description:ImportanceIn the US, transgender, nonbinary, and gender diverse (TGD) adults have high rates of depression. Gender-affirming hormone therapy (GAHT) is associated with improved mental health outcomes, yet existing US studies have short follow ups and lack sample diversity.ObjectiveTo evaluate the use of GAHT delivered in primary care as an intervention for moderate-to-severe depressive symptoms in diverse TGD adult patients.Design, setting, and participantsLEGACY was an observational cohort study conducted in federally qualified community health centers in Boston and New York that followed up TGD patients (N = 3592) from calendar years 2016 to 2019 (48 months). Participants included individuals aged 18 years or older, gender identity different from sex at birth, a past 12-month medical visit, and signed patient consent form in the electronic health record (EHR).ExposuresPrescriptions for GAHT obtained from EHR data, using the date of the first and last GAHT prescription in each calendar year of observation (GAHT within the year vs no GAHT during the year).Main outcomes and measuresA binary outcome of patient-reported moderate-to-severe depressive symptoms was obtained using the validated Patient-Health Questionnaire (PHQ), scoring 10 or greater on the PHQ-9 or scoring 3 or greater on the PHQ-2. Following multiple imputation, generalized estimating equations (GEE) longitudinally modeled GAHT and moderate-to-severe depressive symptoms (n = 20 320 observations) and adjusted for age, gender identity, race and ethnicity, health insurance, federal poverty level, HIV serostatus, number of cohort years, and clinical site.ResultsThe median age of the 3592 patients was 28 (IQR, 24-36) years. Race and ethnicity was diverse (1.3% Asian/Pacific Islander, 11.7% Black, 16.1% Hispanic/Latinx, 63.1% White, 6.8% multiracial, and 1.4% other). In addition, 18.9% were nonbinary, 52.1% lived below the federal poverty level, 34.2% were publicly insured, 4.1% were uninsured, and 5.1% were living with HIV. At baseline, 84.5% of the individuals were prescribed GAHT and 15.3% reported moderate-to-severe depressive symptoms. Patients prescribed GAHT had a statistically significantly lower risk of moderate-to-severe depressive symptoms over follow-up compared with those not prescribed GAHT (adjusted risk ratio, 0.85; 95% CI, 0.75-0.98).Conclusions and relevanceIn this longitudinal observational cohort study, GAHT was associated with lower rates of moderate-to-severe depressive symptoms, highlighting the importance of gender-affirming primary care models for TGD patients.
| S-EPMC11915065 | biostudies-literature