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

Condition(s) studied

Study 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.

Eligibility

Primary outcome measure(s)

• Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy. — At recruitment
  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.
• Changes in endothelial function in the study population. — At recruitment
  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.
• Changes in endothelial function at molecular level in the study population. — At recruitment
  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.
• Changes in the systemic inflammation status in the study population. — At recruitment
  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.
• Changes in the expression of genes related to inflammatory pathways in PBMC in the study population. — At recruitment
  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.
• Changes in the expression of genes related to oxidative stress levels in PBMC in the study population. — At recruitment
  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.
• Changes in the expression of genes related to cellular respiration in PBMC in the study population. — At recruitment
  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.
• Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy. — At recruitment
  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.

Trial sites (1)