Tienforti Daniele, Spagnolo Luca, Piscitani Luca, Tonni Camilla, Donatelli Vittoria, Cordeschi Giuliana, Baroni Marco Giorgio, Barbonetti Arcangelo
Andrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Spinal Unit, San Raffaele Sulmona Institute, Sulmona, Italy.
Front Endocrinol (Lausanne). 2025 Jun 12;16:1537838. doi: 10.3389/fendo.2025.1537838. eCollection 2025.
The impact of testosterone-based gender affirming hormone therapy (T-GAHT) on kidney function in transgender individuals assigned female at birth (AFAB) remains a matter of clinical uncertainty and debate. This study aimed to quantify through a meta-analytical approach the changes in estimated glomerular filtration rate (eGFR), a widely used clinical parameter that reflects how efficiently the kidneys filter waste products from the blood, and in secondary markers of kidney functions in this population during 24 months of GAHT. The eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, which estimates kidney filtration based on serum creatinine, age, and sex.
A thorough search of MEDLINE, COCHRANE LIBRARY, SCOPUS and WEB OF SCIENCE databases was carried out to identify suitable studies. Quality of the articles was scored using the Effective Public Health Practice Project. Data were combined using random effects models and the between-study heterogeneity was assessed using Cochrane's Q and I.
Twenty included studies provided information about an overall sample of 2380 individuals. The pooled estimates documented a significant decrease in eGFR (CKD-EPI equation) at 6 and 12 months with respect to baseline, using the attributed (female) gender. When the CKD-EPI equation was referred to the perceived (male) gender, eGFR significantly decreased after 12 months but not after 6 months of T-GAHT. The trend of eGFR values showed a transient decline during the first year of therapy, followed by stabilization at 18 and 24 months. This pattern is likely attributable to increased creatinine production due to testosterone-induced gains in muscle mass, rather than to a true decline in kidney function. Among the secondary outcomes, pooled estimates revealed significant increases of creatinine and uric acid levels at all follow-up times. On the contrary, blood urea nitrogen (BUN), a waste product filtered by the kidneys and commonly used to assess renal function, did not change significantly after either 6 months or 12 months of T-GAHT.
The influence of T-GAHT on eGFR in the first two years in healthy, young AFAB transgender individuals appears to be statistically significant, but is likely not clinically relevant. This interpretation is supported by the stability of BUN levels and the absence of adverse renal events in the included studies, suggesting preserved kidney function despite changes in creatinine-based estimates. Further research is warranted to identify more accurate tools for evaluating kidney function in this population, particularly during the early months of treatment or in individuals with pre-existing renal conditions.
https://www.crd.york.ac.uk/prospero/, identifier CRD42024596106.
基于睾酮的性别确认激素疗法（T-GAHT）对出生时被指定为女性（AFAB）的跨性别者肾功能的影响在临床上仍存在不确定性且颇具争议。本研究旨在通过荟萃分析方法量化估计肾小球滤过率（eGFR）的变化，eGFR是一种广泛使用的临床参数，反映肾脏从血液中滤过废物的效率，以及该人群在接受24个月性别确认激素疗法期间肾功能的次要指标变化。使用CKD-EPI（慢性肾脏病流行病学协作组）方程计算eGFR，该方程根据血清肌酐、年龄和性别来估计肾脏滤过功能。
全面检索MEDLINE、COCHRANE图书馆、SCOPUS和科学网数据库以识别合适的研究。使用有效公共卫生实践项目对文章质量进行评分。数据采用随机效应模型合并，并使用Cochrane的Q和I统计量评估研究间的异质性。
纳入的20项研究提供了关于2380名个体的总体样本信息。汇总估计显示，按照出生时指定的（女性）性别计算，在6个月和12个月时，eGFR（CKD-EPI方程）相对于基线有显著下降。当CKD-EPI方程按照自我认知的（男性）性别计算时，在接受T-GAHT治疗12个月后eGFR显著下降，但6个月后未下降。eGFR值的趋势显示在治疗的第一年有短暂下降，随后在18个月和24个月时趋于稳定。这种模式可能归因于睾酮诱导的肌肉量增加导致肌酐生成增加，而非肾功能真正下降。在次要结局中，汇总估计显示在所有随访时间肌酐和尿酸水平均显著升高。相反，血尿素氮（BUN）是肾脏滤过的一种废物，常用于评估肾功能，在接受T-GAHT治疗6个月或12个月后均未发生显著变化。
在健康、年轻的AFAB跨性别个体中，T-GAHT在前两年对eGFR的影响在统计学上似乎具有显著意义，但可能在临床上并不相关。这一解释得到了BUN水平的稳定性以及纳入研究中无不良肾脏事件的支持，表明尽管基于肌酐的估计值发生了变化，但肾功能仍保持正常。有必要进行进一步研究以确定更准确的工具来评估该人群的肾功能，特别是在治疗的最初几个月或已有肾脏疾病的个体中。
