Dataset Information

Immune system adaptation during gender-affirming testosterone treatment.

ABSTRACT: 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.

SUBMITTER: Lakshmikanth T

PROVIDER: S-EPMC11374716 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immune system adaptation during gender-affirming testosterone treatment.

Lakshmikanth Tadepally T Consiglio Camila C Sardh Fabian F Forlin Rikard R Wang Jun J Tan Ziyang Z Barcenilla Hugo H Rodriguez Lucie L Sugrue Jamie J Noori Peri P Ivanchenko Margarita M Piñero Páez Laura L Gonzalez Laura L Habimana Mugabo Constantin C Johnsson Anette A Ryberg Henrik H Hallgren Åsa Å Pou Christian C Chen Yang Y Mikeš Jaromír J James Anna A Dahlqvist Per P Wahlberg Jeanette J Hagelin Anders A Holmberg Mats M Degerblad Marie M Isaksson Magnus M Duffy Darragh D Kämpe Olle O Landegren Nils N Brodin Petter P

Nature 20240904 8028

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 beha ...[more]

PMID: 39232147

Similar Datasets

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.

Project description:ImportanceDuring gender-affirming mastectomy, nerves are transected, resulting in sensory loss. Nerve preservation using targeted nipple-areola complex (NAC) reinnervation (TNR) may restore sensation.ObjectiveTo determine the quantitative and patient-reported sensory outcomes of TNR.Design, setting, and participantsProspective matched cohort study of patients undergoing gender-affirming mastectomy from August 2021 to December 2022 at Weill Cornell Medicine and Massachusetts General Hospital. Data were analyzed from January to March 2023.ExposurePatients who underwent TNR and matched patients who did not.Main outcomes and measuresMechanical detection measured with monofilaments and patient-reported outcome questionnaires were completed preoperatively and at 1, 3, 6, 9, and 12 months postoperatively. Additional quantitative sensory testing was performed preoperatively and at 12 months postoperatively. The primary outcome was mechanical detection while secondary outcomes were the additional quantitative sensory testing variables and patient-reported outcomes. Exclusion criteria included peripheral nerve disorders, unmatched patients, and incomplete follow-up.ResultsA total of 25 patients who underwent TNR and 25 matched patients who did not were included. The mean (SD) age was 24.9 (5.5) years, BMI was 26.6 (5.2), and mastectomy weight was 608.9 (326.5) g; 6 patients (12.0%) were Asian, 5 patients (10.0%) were Black or African American, and 33 patients (66.0%) were White. Repeated measures analysis of variance (ANOVA) showed that the outcomes of TNR on improving mechanical detection over time was significant at the NAC (F = 35.2; P < .001) and chest (F = 4.2; P = .045). At 12 months, mean quantitative sensory values in patients who underwent TNR reached baseline and were improved compared with patients who did not undergo TNR for monofilaments (mean [SD] NAC, 3.7 [0.5] vs 4.9 [0.9]; [data]; P < .001; chest, 3.3 [0.4] vs 3.6 [0.6]; [data]; P = .002), vibration (mean [SD] NAC, 7.7 [ 0.4] vs 7.3 [0.4]; t96 = 6.3; P < .001; chest, 7.8 [0.3] vs 7.5 [0.3]; t96 = 5.1; P < .001), 2-point discrimination (NAC, 40% vs 0%; r = 20; P = .02); chest, 4.1 [1.2] cm vs 5.7 [1.8] cm; P < .001), pinprick (mean [SD] NAC, 24.9 [21.2] mN vs 82.6 [96.7] mN; t98 = 4.1; P < .001; chest, 22.5 [25.6] mN vs 54.1 [45.4] mN; t98 = 4.6; P < .001), cold (mean [SD] NAC, 23.1 [4.7] °C vs 12.0 [7.6] °C; t98 = 8.8; P < .001; chest, 23.6 [3.1] °C vs 19.7 [5.6] °C; t98 = 4.4; P < .001), warm (mean [SD] NAC, 39.9 [5.0] °C vs 45.8 [4.2] °C; t98 = 6.3; P < .001; chest, 39.4 [3.1] °C vs 42.9 [4.0] °C; t98 = 4.9; P < .001), and pressure pain detection (mean [SD] NAC, 89.9 [45.6] kPa vs 130.5 [68.9] kPa; t86 = 3.9; P < .001; chest, 128.5 [38.0] kPa vs 175.5 [49.3] kPa; t96 = 4.0; P = .001). ANOVA demonstrated that TNR significantly improved patient-reported nipple sensation (F = 60.5; P < .001), chest light touch (F = 8.1; P = .01) and erogenous sensation (F = 8.3; P = .01). Significantly more patients who underwent TNR than those who did not reported nipple hypersensitivity until 3 months postoperatively (8% vs 4% at 12 months).Conclusion and relevanceIn this prospective matched cohort study, TNR was associated with improved quantitative and patient-reported sensation. Patients should be counseled about the risk of transient NAC hypersensitivity.

Dataset Information

Immune system adaptation during gender-affirming testosterone treatment.

Publications

Immune system adaptation during gender-affirming testosterone treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets