Differences in cardiorespiratory fitness by gonadotropin-releasing hormone agonist treatment before and after testosterone in transgender adolescents.

IF 3.3 3区 医学 Q1 PHYSIOLOGY
Journal of applied physiology Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI:10.1152/japplphysiol.00629.2024
Natalie J Nokoff, Travis Nemkov, Samantha Bothwell, Melanie G Cree, Kelly N Z Fuller, Amy C Keller, Megan M Kelsey, Kristen J Nadeau, Kerrie L Moreau
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引用次数: 0

Abstract

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin-releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to 1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles and 2) evaluate changes after 1 and 12 mo of testosterone therapy among transgender adolescents. Participants assigned female at birth (n = 19, baseline age of 15.0 ± 1.0 yr) from two groups: GnRHa+ (n = 8) and GnRHa- (n = 11) were examined at baseline and 1- and 12-mo post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration, and metabolic profile. Fasted morning labs included assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 mo, and 12 mo), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative V̇o2peak (30.1 ± 4.83 vs. 25.24 ± 4.47 mL/kg/min, P = 0.042) than GnRHa- individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (P = 0.011) and total exercise time (P = 0.005) after 12 mo of testosterone (P = 0.012) but not GnRHa- individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (P = 0.0007) and lipid (P = 0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy.NEW & NOTEWORTHY This study demonstrates differences in exercise capacity and mitochondrial respiration at baseline based on whether or not individuals had feminizing puberty blocked. Individuals who had puberty blocked had greater improvements in cardiopulmonary exercise testing parameters after 12 mo of testosterone than those who went through feminizing puberty.

变性青少年在使用睾酮后,促性腺激素释放激素激动剂治疗对心肺功能影响的基线差异趋于一致。
众所周知,心肺功能(CRF)存在性别差异。对于变性青少年使用促性腺激素释放激素激动剂(GnRHa)阻断青春期发育后再进行激素治疗对 CRF 的影响,目前还知之甚少。我们的目的是:(1)确定 GnRHa 单药治疗对 CRF 和线粒体功能的影响以及与代谢组学特征的关联;(2)评估变性青少年接受睾酮治疗 1 个月和 12 个月后的变化。两组出生时被分配为女性的参与者(19 人,基线年龄为 15.0+1.0 岁):在一项纵向观察研究中,对 GnRHa+ 组(8 人)和 GnRHa- 组(11 人)进行了基线、睾酮治疗后 1 个月和 12 个月的检查,以评估心肺功能、线粒体呼吸和代谢状况。清晨禁食实验包括评估代谢组学、外周血单核细胞线粒体呼吸和线粒体耦合度(呼吸控制比,RCR)。进行分级循环测力计测试。评估了各组之间的基线差异。通过混合线性回归模型对时间(基线、1 个月和 12 个月)、组别(GnRHa 治疗是/否)及其交互作用进行评估,比较各组别的变化。基线时,GnRHa+患者的相对 VO2 峰值(30.1+4.83 vs. 25.24+4.47 ml/kg/min,p=0.042)高于 GnRHa- 患者。在回归模型中,服用睾酮 12 个月后,GnRHa+ 人的峰值瓦特数(p=0.011)和总运动时间(p=0.005)显著增加(p=0.012),而 GnRHa- 人则没有。在碳水化合物(p=0.0007)和脂质(p=0.0002)条件下,GnRHa+个体的RCR明显高于GnRHa+个体。GnRHa预处理对接受睾酮治疗的青少年变性男性的峰值CRF和线粒体呼吸有积极影响。
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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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