Effects of Gender-Affirming Hormone Therapy on Cardiovascular, Metabolic, and Mental Health Outcomes in Transgender Adults.

NCT07394400 | Not Yet Recruiting

• 1 other identifier: PI25/01841
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this observational study is to examine the impact of gender-affirming hormone therapy (GAHT) on mood in transgender individuals and to explore its potential association with early atherosclerotic processes. The main questions it aims to answer are:

• Whether GAHT in transgender individuals has a psychological and functional impact, assessed through mood, stress, and self-esteem. Additionally, the study will analyze whether morphofunctional changes (including body composition, muscle strength, cardiorespiratory fitness, and metabolic flexibility) are related to inflammatory responses and psychological well-being.
• Whether the administration of GAHT poses a cardiovascular risk by influencing biochemical, inflammatory, and oxidative markers, mitochondrial function, and the activation of the NLRP3 inflammasome in leukocytes. Participants will undergo evaluation of early stages of the atherosclerotic process through the analysis of leukocyte-endothelial interactions, adhesion molecule expression, and ankle-brachial index (ABI), as well as periodontal parameters. Overall, this study aims to contribute to improving healthcare delivery and promoting more equitable and gender-affirming medical services tailored to the needs of transgender individuals.

Conditions

Transgender Individuals

Keywords

GAHT; inflammation; atherosclerosis; periodontal disease; Transgender

Outcome Measures

Primary Outcomes (8)

• Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy.

  Relative protein expression of NLRP3, ASC, Caspase-1 and inflammatory mediators NFκB, JNK by Western Blot and normalized to the loading control protein in PBMC. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in endothelial function in the study population.

  Evaluation of leucocytes adhesion to the endothelial cell in vitro by means of a parallel flow chamber system coupled to an inverted phase-contrast microscope. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in endothelial function at molecular level in the study population.

  Evaluation of circulating levels of adhesion molecules - P-selectin, ICAM-1, and VCAM-1, levels of the pro-oxidant enzyme MPO and circulating cytokines (L1β, IL18, IL6, IL10 and TNFα) in serum using Luminex technique. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in the systemic inflammation status in the study population.

  Evaluation of circulating levels of mtDNA in serum samples using RT-PCR. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in the expression of genes related to inflammatory pathways in PBMC in the study population.

  Identification of altered messengers using a metabolic multiplex panel, evaluating genes of interest in inflammatory pathways (TLR and NFkB), oxidative stress, cytokine signalling, and mitochondrial respiration. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in the expression of genes related to oxidative stress levels in PBMC in the study population.

  Relative expression of genes related to oxidative stress (SOD1, NRF2, GSR, GPX1, GCLC, GCLM and TXNRD1) by PCR real time. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in the expression of genes related to cellular respiration in PBMC in the study population.

  Relative expression of pro and antioxidants enzimes (NADPH oxidase, catalase, GPX1, SOD1, and NFR2) and genes related to mitochondrial respiration (I, II, III, IV and V complexes) and PGC1α in PBMC by WB. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

• Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy.

  Study of inflammasome assembly by confocal microscopy in PBMC. This measurement will be taken at the start, and at 6 and 12 months of THAG.

  At recruitment

Secondary Outcomes (2)

• Evaluation of redox status (PBMCs and PMNs) in the study population.

  At recruitment

• Evaluation of mitochondrial function of leukocytes (PBMCs and PMNs) in the study population.

  At recruitment

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Transgender individuals referred to a Gender Identity Unit who are requesting Gender Affirmation Hormone Therapy for the first time. It will consist of three visits: at the start, and after 6 and 12 months of treatment.

You may qualify if:

• Trans men and trans women over the age of 16

You may not qualify if:

• systemic inflammatory diseases
• uncontrolled infections
• severe autoimmune diseases intersex biological conditions (resistance, severe sexual development or chromosomal abnormalities, congenital adrenal hyperplasia)
• treatment with metformin, statins or oral contraceptives in the previous 6 months
• serious life-threatening diseases
• diseases that compromise follow-up
• BMI higher than 35

Sponsors & Collaborators

• Milagros Rocha Barajas: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital Universitario Doctor Peset

Valencia, Valencia, 46017, Spain

Location

Related Publications (11)

• Koukoulis GN, Filiponi M, Gougoura S, Befani C, Liakos P, Bargiota Alpha. Testosterone and dihydrotestosterone modulate the redox homeostasis of endothelium. Cell Biol Int. 2022 Apr;46(4):660-670. doi: 10.1002/cbin.11768. Epub 2022 Jan 30.

  PMID: 35066972 BACKGROUND

• Exposito-Campos P, Gomez-Balaguer M, Hurtado-Murillo F, Morillas-Arino C. Evolution and trends in referrals to a specialist gender identity unit in Spain over 10 years (2012-2021). J Sex Med. 2023 Feb 27;20(3):377-387. doi: 10.1093/jsxmed/qdac034.

  PMID: 36763946 BACKGROUND

• Banuls C, Rovira-Llopis S, Martinez de Maranon A, Veses S, Jover A, Gomez M, Rocha M, Hernandez-Mijares A, Victor VM. Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS. Metabolism. 2017 Jun;71:153-162. doi: 10.1016/j.metabol.2017.02.012. Epub 2017 Feb 27.

  PMID: 28521868 BACKGROUND

• Zhang Q, Goodman M, Adams N, Corneil T, Hashemi L, Kreukels B, Motmans J, Snyder R, Coleman E. Epidemiological considerations in transgender health: A systematic review with focus on higher quality data. Int J Transgend Health. 2020 Apr 15;21(2):125-137. doi: 10.1080/26895269.2020.1753136. eCollection 2020.

  PMID: 33015664 BACKGROUND

• Victor VM, Rovira-Llopis S, Banuls C, Diaz-Morales N, Castello R, Falcon R, Gomez M, Rocha M, Hernandez-Mijares A. Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance. Eur J Endocrinol. 2015 Nov;173(5):683-91. doi: 10.1530/EJE-15-0572. Epub 2015 Aug 28.

  PMID: 26320144 BACKGROUND

• Villar CC, Sloniak MC, de Assis JB, Porto RC, Romito GA. Unveiling sex-disparities and the impact of gender-affirming hormone therapy on periodontal health. Front Dent Med. 2024 Sep 16;5:1430193. doi: 10.3389/fdmed.2024.1430193. eCollection 2024.

  PMID: 39917660 BACKGROUND

• Nokoff NJ, Nemkov T, Bothwell S, Cree MG, Fuller KNZ, Keller AC, Kelsey MM, Nadeau KJ, Moreau KL. Differences in cardiorespiratory fitness by gonadotropin-releasing hormone agonist treatment before and after testosterone in transgender adolescents. J Appl Physiol (1985). 2024 Nov 1;137(5):1470-1483. doi: 10.1152/japplphysiol.00629.2024. Epub 2024 Oct 17.

  PMID: 39417821 BACKGROUND

• Cheung AS, Zwickl S, Miller K, Nolan BJ, Wong AFQ, Jones P, Eynon N. The Impact of Gender-Affirming Hormone Therapy on Physical Performance. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e455-e465. doi: 10.1210/clinem/dgad414.

  PMID: 37437247 BACKGROUND

• Lakshmikanth T, Consiglio C, Sardh F, Forlin R, Wang J, Tan Z, Barcenilla H, Rodriguez L, Sugrue J, Noori P, Ivanchenko M, Pinero Paez L, Gonzalez L, Habimana Mugabo C, Johnsson A, Ryberg H, Hallgren A, Pou C, Chen Y, Mikes J, James A, Dahlqvist P, Wahlberg J, Hagelin A, Holmberg M, Degerblad M, Isaksson M, Duffy D, Kampe O, Landegren N, Brodin P. Immune system adaptation during gender-affirming testosterone treatment. Nature. 2024 Sep;633(8028):155-164. doi: 10.1038/s41586-024-07789-z. Epub 2024 Sep 4.

  PMID: 39232147 BACKGROUND

• Glintborg D, Christensen LL, Andersen MS. Transgender healthcare: metabolic outcomes and cardiovascular risk. Diabetologia. 2024 Nov;67(11):2393-2403. doi: 10.1007/s00125-024-06212-6. Epub 2024 Jul 3.

  PMID: 38958699 BACKGROUND

• Coleman E, Radix AE, Bouman WP, Brown GR, de Vries ALC, Deutsch MB, Ettner R, Fraser L, Goodman M, Green J, Hancock AB, Johnson TW, Karasic DH, Knudson GA, Leibowitz SF, Meyer-Bahlburg HFL, Monstrey SJ, Motmans J, Nahata L, Nieder TO, Reisner SL, Richards C, Schechter LS, Tangpricha V, Tishelman AC, Van Trotsenburg MAA, Winter S, Ducheny K, Adams NJ, Adrian TM, Allen LR, Azul D, Bagga H, Basar K, Bathory DS, Belinky JJ, Berg DR, Berli JU, Bluebond-Langner RO, Bouman MB, Bowers ML, Brassard PJ, Byrne J, Capitan L, Cargill CJ, Carswell JM, Chang SC, Chelvakumar G, Corneil T, Dalke KB, De Cuypere G, de Vries E, Den Heijer M, Devor AH, Dhejne C, D'Marco A, Edmiston EK, Edwards-Leeper L, Ehrbar R, Ehrensaft D, Eisfeld J, Elaut E, Erickson-Schroth L, Feldman JL, Fisher AD, Garcia MM, Gijs L, Green SE, Hall BP, Hardy TLD, Irwig MS, Jacobs LA, Janssen AC, Johnson K, Klink DT, Kreukels BPC, Kuper LE, Kvach EJ, Malouf MA, Massey R, Mazur T, McLachlan C, Morrison SD, Mosser SW, Neira PM, Nygren U, Oates JM, Obedin-Maliver J, Pagkalos G, Patton J, Phanuphak N, Rachlin K, Reed T, Rider GN, Ristori J, Robbins-Cherry S, Roberts SA, Rodriguez-Wallberg KA, Rosenthal SM, Sabir K, Safer JD, Scheim AI, Seal LJ, Sehoole TJ, Spencer K, St Amand C, Steensma TD, Strang JF, Taylor GB, Tilleman K, T'Sjoen GG, Vala LN, Van Mello NM, Veale JF, Vencill JA, Vincent B, Wesp LM, West MA, Arcelus J. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. Int J Transgend Health. 2022 Sep 6;23(Suppl 1):S1-S259. doi: 10.1080/26895269.2022.2100644. eCollection 2022.

  PMID: 36238954 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, neutrophils and Peripheral Blood Mononuclear Cells

MeSH Terms

Conditions

Inflammation; Atherosclerosis; Periodontal Diseases

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Milagros Rocha, PhD

  FISABIO-HOSPITAL DR PESET

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miagros Rocha, PhD

CONTACT

963189132; milagros.rocha@fisabio.es

Sandra López, PhD

CONTACT

963188879; sandra.lopez@fisabio.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Postdoctoral Researcher

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: February 6, 2026
• Study Start: February 14, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 6, 2026

Record last verified: 2025-10

Locations

ES (1)