A systematic review of psychosocial functioning changes after gender-affirming hormone therapy among transgender people.
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ABSTRACT:
SUBMITTER: Doyle DM
PROVIDER: S-EPMC10444622 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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A systematic review of psychosocial functioning changes after gender-affirming hormone therapy among transgender people.
Doyle David Matthew DM Lewis Tom O G TOG Barreto Manuela M
Nature human behaviour 20230522 8
This systematic review assessed the state and quality of evidence for effects of gender-affirming hormone therapy on psychosocial functioning. Forty-six relevant journal articles (six qualitative, 21 cross-sectional, 19 prospective cohort) were identified. Gender-affirming hormone therapy was consistently found to reduce depressive symptoms and psychological distress. Evidence for quality of life was inconsistent, with some trends suggesting improvements. There was some evidence of affective cha ...[more]
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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: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
Project description:Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40-0.83; p < 0.0001; I2 = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term.
| S-EPMC11531450 | biostudies-literature
Project description:IntroductionGender-affirming hormone therapy (GAHT) and gender-affirming surgery (GAS) may be desired by transgender and gender-diverse (TGD) individuals who want to affirm their gender identity. Testosterone is the basis of GAHT for transgender individuals assigned female at birth (AFAB), whereas GAS can involve hysterectomy, bilateral salpingectomy, bilateral oophorectomy (BO), thorax masculinization, and phalloplasty. Our study aimed to evaluate the effects of GAHT on the bone health of TGD AFAB individuals who have undergone or not undergone BO.MethodsThis was a single-center, longitudinal study with retrospectively collected data. TGD AFAB GAHT-naïve individuals were enrolled and underwent dual-energy X-ray absorptiometry scans and laboratory tests (hormonal and bone metabolism parameters) at baseline and after 5 and 10 years of GAHT.ResultsTwo hundred and forty-three TGD AFAB people were included in this study. Seventy-five subjects had completed data for 5 years and 19 subjects for 10 years of GAHT. At baseline, low bone density (Z-score < -2.0) was found in 2.5% (6/243) of subjects for lumbar spine (LS), whereas total hip (TH) and femoral neck (FN) Z-scores and laboratory tests were within the normal female range. After stratifying by physical activity, the physically active group showed significantly higher LS BMD and Z-scores (p ≤ 0.05). Five years after the start of GAHT, a significant reduction in LS (p ≤ 0.05), TH (p ≤ 0.001), and FN (p ≤ 0.01) Z-scores was detected. A significant reduction in the Z-scores of all three bone sites was observed only in the subgroup that had undergone BO. After 5 years of GAHT, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.001). Significantly higher estradiol levels were detected in the 5-year no-BO subgroup compared to those in the 5-year BO subgroup (p ≤ 0.001). A significant reduction in LS and TH Z-scores were observed after 10 years of GAHT. At this time, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.01).ConclusionBone density in TGD AFAB individuals is comparable to that in their peers prior to GAHT and BO, but those subjects who underwent BO had a reduced Z-score at LS, FN, and TH after 5 years and at LS after 10 years of GAHT.
| S-EPMC11464845 | biostudies-literature
Project description:BackgroundGender-affirming hormone therapy (GAHT) is prescribed to produce secondary sex characteristics aligning external anatomy with gender identity to mitigate gender dysphoria. Transgender women are generally treated with oestrogens and anti-androgens, whereas transgender men are treated with testosterone. The objective of this narrative review was to characterise the influence of GAHT on body composition and bone health in the transgender population to help address weight concerns and chronic disease risk.MethodsStudies were extracted from PubMed and Scopus and limited to only those utilising imaging technologies for precise adipose tissue, lean mass, and bone mineral density (BMD) quantification.ResultsAlthough methodologies differed across the 20 investigations that qualified for inclusion, clear relationships emerged. Specifically, among transgender women, most studies supported associations between oestrogen therapy and decreases in lean mass and increases in both, fat mass and body mass index (BMI). Within transgender men, all studies reported associations between testosterone therapy and increases in lean mass, and although not as consistent, increases in BMI and decreases in fat mass. No consistent changes in BMD noted for either group.ConclusionsAdditional research is needed to appropriately assess and evaluate the implications of these body composition changes over time (beyond 1 year) in larger, more diverse groups across all BMI categories. Future studies should also seek to evaluate nutrient intake, energy expenditure and other important lifestyle habits to diminish health disparities within this vulnerable population. Policies are needed to help integrate registered dietitians into the routine care of transgender individuals.
| S-EPMC9790536 | biostudies-literature
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:The main objective was to carry out a prospective global CpG (cytosine-phosphate-guanine) methylation analysis before vs. after six months of gender affirming hormone treatment (GAHT), in a transgender population vs. a cisgender population.
2021-05-03 | GSE173717 | GEO
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:BackgroundTransgender patients often cannot access a provider who is knowledgeable about providing gender-affirming hormone therapy (GAHT). This study evaluated primary care provider (PCP) comfort and experience with, opinions about, and knowledge of prescribing GAHT to adults.MethodsAn anonymous Qualtrics survey was distributed to PCPs in San Diego County. Fisher's exact test assessed any association between age, years in practice, or practice setting and 1) comfort in prescribing GAHT and 2) favorable statements about learning about, providing, and benefitting from training in GAHT. T-tests determined relationship between age, years in practice, or practice type setting with number of correctly answered multiple choice knowledge-based questions out of 4.ResultsOut of 220 responses, median age was 41, 60% had practiced for ≤ 10 years, and 19% had practiced in an academic setting. Forty-two percent did not receive any education about transgender healthcare during medical training. The most commonly reported barrier to providing GAHT was lack of training (74%). PCPs age ≤ 41 (67% vs 49%, p = 0.009), PCPs practicing for ≤ 10 years (65% vs 51%, p = 0.037), and PCPs in non-academic settings (64% vs. 41%, p = 0.013) were more likely to report being comfortable with prescribing GAHT. PCPs age ≤ 41 (89% vs 62%, p < 0.001) and PCPs practicing for ≤ 10 years (86% vs 66%, p < 0.001) were more likely to show interest in learning about GAHT. PCPs age ≤ 41 (74% vs 46%, p < 0.001) and PCPs practicing for ≤ 10 years (70% vs 50%, p = 0.003) were more likely to show interest in prescribing GAHT. Knowledge scores were higher for PCPs age ≥42 (mean 1.7 vs 1.4, p = 0.033) and PCPs working in academic centers (mean 2.0 vs 1.4, p = 0.002).ConclusionYounger (age ≤ 41) and early career (practicing for ≤ 10 years) PCPs reported being more comfortable with prescribing GAHT and had more favorable opinions in learning about, providing, and benefitting from training in GAHT. They are interested in providing GAHT; however, few prescribe GAHT with most reporting lack of training as a major barrier. This was evident with overall low knowledge scores regardless of age, experience, or clinical setting and underscores the need for increased educational efforts in transgender care throughout medical training.
| S-EPMC11481314 | biostudies-literature
Project description:Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has a direct translational benefit for TNG individuals on gender-affirming hormone therapies (GAHTs). Despite this potential, endocrinological health care for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique health care needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHTs will greatly benefit the health care outcomes of TNG people.
| S-EPMC10472479 | biostudies-literature