Dataset Information

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

ABSTRACT:

Background

Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity.

Methods

Individuals with gender dysphoria and cisgender controls underwent 2 MRI measurements, with a median interval of 145 days (interquartile range [IQR] 128.25-169.75 d, mean 164.94 d) between the first and second MRI. Transgender women (TW) and transgender men (TM) underwent the first MRI before GHT and the second MRI after approximately 4.5 months of GHT, which comprised estrogen and anti-androgen therapy in TW or testosterone therapy in TM. Hypothalamic volumes were segmented using FreeSurfer, and effects of GHT were tested using repeated-measures analysis of covariance.

Results

The final sample included 106 participants: 38 TM, 15 TW, 32 cisgender women (CW) and 21 cisgender men (CM). Our analyses revealed group × time interaction effects for total, left and right hypothalamus volume, and for several subunits (left and right inferior tubular, left superior tubular, right anterior inferior, right anterior superior, all p _corr < 0.01). In TW, volumes decreased between the first and second MRI in these regions (all p _corr ≤ 0.01), and the change from the first to second MRI in TW differed significantly from that in CM and CW in several subunits (p _corr < 0.05).

Limitations

We did not address the influence of transition-related psychological and behavioural changes.

Conclusion

Our results suggest a subunit-specific effect of GHT on hypothalamus volumes in TW. This finding is in accordance with previous reports of positive and negative effects of androgens and estrogens, respectively, on cerebral volumes.

SUBMITTER: Konadu ME

PROVIDER: S-EPMC10521920 | biostudies-literature | 2023 Sep-Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Konadu Melisande E ME Reed Murray B MB Kaufmann Ulrike U Handschuh Patricia A PA Spurny-Dworak Benjamin B Klöbl Manfred M Schmidt Clemens C Godber Godbersen M M Briem Elisa E Seiger René R Baldinger-Melich Pia P Kranz Georg S GS Lanzenberger Rupert R Spies Marie M

Journal of psychiatry & neuroscience : JPN 20230926 5

<h4>Background</h4>Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity.<h4>Methods</h4>Individuals with gender dysphoria and cisgend ...[more]

PMID: 37751919

Similar Datasets

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.

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.

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.

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.

Dataset Information

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Background

Methods

Results

Limitations

Conclusion

Publications

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets