Testosterone is the primary male sex hormone, playing a significant role in developing male characteristics, maintaining bone density, and regulating muscle mass. The use of Testosterone Replacement Therapy (TRT) has increased substantially as a treatment for hypogonadism (abnormally low testosterone levels). As more people explore this hormonal therapy, questions have arisen regarding its potential side effects, including whether it increases the risk of developing kidney stones. This analysis explores the current scientific understanding of the relationship between testosterone and the formation of urinary stones.
Understanding the Link Between Testosterone and Kidney Stone Risk
The relationship between testosterone levels and kidney stone formation is complex, suggesting a nuanced connection rather than a simple cause-and-effect. Some large-scale studies show that men undergoing TRT have a statistically higher risk of experiencing a stone-related event over a two-year period compared to matched hypogonadal men not on therapy. This increased risk was observed primarily in those using topical gels and injectable forms of testosterone.
Other population-based data indicate that low testosterone levels are also associated with an increased prevalence of kidney stones, especially in older men. This suggests the hormonal environment is involved in stone risk, but the impact is not solely tied to high levels. The general male population experiences kidney stones two to three times more frequently than the female population, a disparity often attributed to higher baseline testosterone levels. The biological plausibility that pharmacological testosterone levels can alter the urinary environment is strong.
Metabolic Pathways Affected by Testosterone
Testosterone influences the body’s chemistry in ways that promote mineral crystallization and stone formation in the kidney. One primary mechanism involves calcium regulation, which can be altered by high testosterone levels. Research indicates that testosterone can increase the amount of calcium excreted into the urine, a condition known as hypercalciuria.
Calcium Regulation
This effect occurs because testosterone inhibits the function of a specific calcium transporter protein in the kidney called TRPV5. Suppressing this protein means the kidney reabsorbs less calcium back into the bloodstream. This excess calcium passes into the urine, where it can combine with oxalate to form calcium oxalate stones, the most common type of kidney stone.
Oxalate and Inhibitors
Testosterone also affects the metabolism of oxalate. The hormone may enhance the activity of a liver enzyme called glycolate oxidase (GAO). Increased GAO activity results in higher levels of urinary oxalate, leading to hyperoxaluria.
Testosterone has also been linked to changes in the excretion of uric acid and citrate. Citrate is a natural inhibitor of stone formation because it binds to calcium in the urine. By potentially suppressing citrate excretion while simultaneously increasing uric acid and oxalate, testosterone creates factors that favor stone development.
Identifying Patient-Specific Risk Factors
A patient’s individual risk profile determines whether testosterone’s metabolic effects will translate into stone formation. The largest predictor of a new kidney stone event is a personal history of having had a stone previously. Patients with a known history of stone disease must be monitored closely when initiating TRT.
The method and dose of TRT delivery also affect risk, suggesting that supraphysiological peaks in testosterone are a factor. Studies found that topical and injectable testosterone, which create sharper peaks in circulating hormone levels, are associated with a greater increase in stone events than pellet therapy. This highlights the role of high-normal or above-normal testosterone concentrations in driving adverse metabolic changes.
Concurrent health issues that independently increase stone risk can compound the effects of TRT. Conditions linked with low testosterone, such as gout, obesity, or metabolic syndrome, are risk factors for stone formation due to their impact on urinary chemistry. Lifestyle factors also contribute significantly, including a high-salt or high-protein diet, chronic dehydration, and low physical activity.
Strategies for Monitoring and Prevention
Proactive monitoring is necessary for individuals on TRT concerned about stone risk. Before starting therapy, a healthcare provider should conduct baseline screening, typically including a comprehensive metabolic panel to assess kidney function and a urinalysis to check for basic indicators of stone risk.
For patients with an elevated risk, such as those with a stone history, a 24-hour urine collection is often recommended to measure specific stone-forming and stone-inhibiting substances. This test quantifies urinary levels, providing a precise chemical profile that guides targeted prevention strategies. The substances measured include:
- Calcium
- Oxalate
- Uric acid
- Citrate
Aggressive hydration is the most effective prevention method, aiming for a urine output of at least two to two and a half liters daily. Dietary modifications should focus on reducing high-sodium and high-animal-protein intake, which can increase calcium and uric acid excretion. Patients should seek immediate consultation if they experience symptoms like severe flank pain, blood in the urine, or persistent nausea, as these may signal a developing stone.