Testosterone did not predict measured GFR decline over 11 years in middle-aged men

Design

Population-based prospective cohort with repeated iohexol clearance (RENIS)

Population

800 men aged 50–62 without diabetes, CVD or kidney disease (Norway)

Primary outcome

Annual change in measured GFR and accelerated decline

Effect

Total testosterone −0.02 (95% CI −0.04 to 0.01) mL/min/1.73 m² per year per nmol/L; no association

The Renal Iohexol Clearance Survey (RENIS) in Tromsø, Norway, enrolled a representative sample of 800 men aged 50 to 62 from the general population, without self-reported diabetes, cardiovascular or kidney disease. GFR was measured directly by plasma iohexol clearance in 2007 to 2009, then again in 2013 to 2015 (656 men) and 2018 to 2020 (578 men).

Higher total testosterone and SHBG were associated with slightly higher baseline GFR (0.27 mL/min/1.73 m² per nmol/L of testosterone). But neither total testosterone, free testosterone nor SHBG was associated with the rate of GFR decline over a median 10.9 years (for example −0.02 mL/min/1.73 m² per year per nmol/L of testosterone, 95% CI −0.04 to 0.01), or with the steepest 10% of decline.

Earlier studies suggesting testosterone speeds kidney decline used creatinine-based eGFR, which is distorted by muscle mass, and muscle mass rises with testosterone. Measured GFR removes that bias. The finding does not address testosterone therapy or anabolic steroid misuse.

• Natural testosterone levels in middle-aged men were not associated with faster measured GFR decline.
• Creatinine-based eGFR is biased by muscle mass; interpret it cautiously in very muscular patients.
• Where eGFR and body build disagree, consider cystatin C-based eGFR.
• This does not address testosterone replacement or anabolic steroid use, which have separate kidney concerns.

Why it matters

It shows how a biomarker bias can create an apparent risk factor, and how measured GFR corrects it.

Don't overread it

Observational, in men aged 50 to 62 without diabetes, cardiovascular or kidney disease; associations, not causes.

The statistics, in plain English

The confidence interval for the effect on GFR decline (−0.04 to 0.01 mL/min per year per nmol/L) includes zero and is very narrow, so any real effect would be tiny. Loss to follow-up (578 of 800 at the last visit) could bias results if those who left differed.

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