Unveiling mechanisms underlying kidney function changes during sex hormone therapy

SA van Eeghen; Pyle L; Narongkiatikhun P; Choi YJ; Obeid W; Parikh CR; Vosters TG; van Valkengoed  IG; Krebber MM; Touw DJ; den Heijer  M; Bjornstad P; van Raalte DH; Nokoff NJ

doi:10.1530/ey.22.6.16

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 6.16 | DOI: 10.1530/ey.22.6.16

ESPEYB25 6. DSD and Gender Incongruence Gender Incongruence: Sex Hormones and Kidney Function (1 abstracts)

6.16. Unveiling mechanisms underlying kidney function changes during sex hormone therapy

van Eeghen SA , Pyle L , Narongkiatikhun P , Choi YJ , Obeid W , Parikh CR , Vosters TG , van Valkengoed IG , Krebber MM , Touw DJ , den Heijer M , Bjornstad P , van Raalte DH & Nokoff NJ

J Clin Invest. 2025 Mar 25;135(9):e190850. doi: 10.1172/JCI190850

Brief summary: This prospective study assessed changes in kidney function in 23 transgender women (registered sex at birth male) and 21 transgender men. In transgender women GFR (measured using iohexol clearance) increased by 3.6% and effective renal plasma flow (ERPF, measured via para-aminohippuric acid clearance) increased by 9.1% during three months of feminising hormone treatment (estradiol and an anti-androgen). Several tubular injury biomarkers decreased. In transgender men no significant changes of GFR or ERPF were observed during three months of testosterone treatment whereas two tubular injury biomarkers increased. Proteomic analysis identified potential mediators of the effects of sex steroids.

Previous studies have reported changes in kidney function parameters such as creatinine and cystatin C in transgender individuals undergoing hormone treatment, but these are also influenced by body composition. In addition, when estimating GFR from creatinine or cystatin C, different formulas are used for male or female sex, which produce substantially different results (1). This complicates their use in the assessment of kidney function in transgender people. The recent study by van Eeghen et al. used the gold-standard methods to measure GFR and ERPF. The observed enhanced kidney function during feminising hormone treatment did not seem to be associated with glomerular hyperfiltration but rather suggested a state of afferent vasodilation induced by increased estradiol and decreased testosterone concentrations. A renoprotective effect of estradiol may explain the slower progression of chronic kidney disease in women compared to men. What the clinical significance is of the increased level of two kidney injury biomarkers that may indicate tubular stress in transgender men deserves further study.

Reference: 1. van Eeghen SA, Wiepjes CM, T’Sjoen G, Nokoff NJ, den Heijer M, Bjornstad P, van Raalte DH. Cystatin C-Based eGFR Changes during Gender-Affirming Hormone Therapy in Transgender Individuals. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1545-1554. PMID: 37678248.