A Comprehensive Assessment of the Impact of Gender-Affirming Hormone Therapy on Cardiovascular Risk, Metabolic Health, and Mood Disorders in Transgender Individuals.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy.
研究概览
简要总结
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.
详细描述
Blood samples will be collected from patients at baseline (before starting gender-affirming hormone therapy), 6 and 12 months after. From fasting blood samples (12h), peripheral blood mononuclear cells (PBMCs) and neutrophil fractions will be isolated using an immunomagnetic method, following the manufacturer's protocol, and plasma and serum will be stored at -80°C until analysis. LUNA-FL will be used to determine cell count and viability (acridine orange and propidium iodide double stain) in cell samples.
For periodontal assessment participants will undergo a comprehensive periodontal examination to determine several gingival parameters, including probing depth (PD), clinical attachment loss (CAL), bleeding index, plaque index, and calculus. Based on these data, the presence or absence of periodontal disease, as well as its extent when present, will be diagnosed.
Biochemical parameters of carbohydrate metabolism - glucose, insulin, glycated hemoglobin (A1c) -, lipid profile - total cholesterol, LDL, HDL, triglycerides (TG), apolipoproteins AI and B -, emerging inflammatory and cardiovascular risk markers - C-Reactive Protein (CRP), C3c, and retinol-binding protein 4 (RBP4) -, and complete blood count will be determined at the hospital's Clinical Analysis Service. Weight, height, and blood pressure will be measured using standardized methods.
Morphofunctional changes will be assessed at baseline and after 12 months of GAHT. Participants will attend the Morphofunctional Assessment Unit after an overnight fast. Body composition and hydration status will be measured using bioelectrical impedance analysis (mBCA 520, SECA, Germany). The quality and distribution of adipose and muscle tissue will be evaluated through Nutritional Ultrasound® using a DP-50 Expert Mobile Ultrasound System (Mindray®) equipped with a multifrequency linear transducer (5-10 MHz). Measurements will be performed in B-mode following established methodological recommendations (10.1016/j.endinu.2022.03.008).
For evaluation of cardiorrespiratory fitness through an incremental ramp exercise test on a cycle ergometer (Ergoselect 200 P, Ergoline, Germany) performed to voluntary exhaustion, following established recommendations (10.1152/ajpregu.00126.2020.0363-6119/20), to determine VO₂max and ventilatory thresholds. A COSMED K5 metabolic analyzer (COSMED, Italy) will be used for gas exchange analysis. Blood pressure, heart rate (Polar H10 heart rate monitor; Polar Electro Oy, Finland), and oxygen saturation at both systemic and muscular levels (WristOx2 3150, Nonin Medical Inc., USA; and Moxy®, Fortiori Design LLC, USA, respectively) will be continuously monitored. Maximal isometric strength of the knee extensor muscles will be measured using a MicroFET2 dynamometer (Hoggan Scientific LLC, USA), and resting metabolic rate (RMR) will also be assessed with the COSMED K5 metabolic analyzer.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Trans men and trans women over the age of 16
排除标准
- •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
结局指标
主要结局
Changes in the degree of activation of the inflammasome complex in transgender individuals following gender-affirming hormone therapy.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
次要结局
- 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)
研究者
Milagros Rocha Barajas
Senior Postdoctoral Researcher
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana