Testosterone is the primary male sex hormone, regulating muscle mass, bone density, and reproductive function. Kidney stones (nephrolithiasis) are hard, crystalline mineral deposits that form within the kidneys or urinary tract. The question of whether testosterone—whether naturally high or administered as therapy—influences the formation of these stones has been a subject of ongoing medical investigation. This article examines the clinical data and physiological mechanisms linking testosterone levels to kidney stone development.
Clinical Findings on Testosterone and Stone Incidence
The clinical evidence regarding testosterone’s relationship with stone formation presents a complex picture. Some large-scale studies on men undergoing Testosterone Replacement Therapy (TRT) for hypogonadism observed a higher rate of stone-related events compared to men not receiving the treatment. For instance, an analysis of over 50,000 hypogonadal men found a significant increase in the absolute risk of stone events over a two-year period for those on TRT. The elevated risk was noted across men receiving injectable and topical forms of the hormone.
However, other large population-based surveys suggest that the opposite may be true for older men, finding that lower serum testosterone levels are associated with a greater prevalence of kidney stones. This conflicting data suggests that the link is not a simple linear one, but is likely affected by age, pre-existing metabolic conditions, and the specific hormone dose. The relationship appears dose-dependent: pharmacological elevation via TRT may increase risk, while low levels in aging men may also be associated with higher stone incidence.
The Role of Hormones in Renal Stone Formation
The physiological mechanisms connecting testosterone and stone risk are rooted in how the hormone alters the body’s mineral and metabolite balance. Testosterone promotes the crystallization of calcium oxalate, the most common type of kidney stone, by affecting oxalate metabolism. The hormone increases the activity of the liver enzyme glycolic acid oxidase (GAO), which synthesizes urinary oxalate. This increase leads to hyperoxaluria, an excessive amount of oxalate in the urine, setting the stage for stone formation.
Testosterone may also interfere with the kidney’s natural defense system against crystal aggregation. Androgens can suppress the expression of osteopontin, a glycoprotein that inhibits calcium oxalate crystal growth in the renal tubules. By reducing this protective factor while simultaneously increasing stone-forming compounds like oxalate, testosterone creates a more lithogenic, or stone-forming, urinary environment. This mechanism helps explain why men, who naturally have higher testosterone levels, experience kidney stones approximately three times more often than women.
Primary Causes of Kidney Stones
While hormonal factors contribute to the gender disparity in stone incidence, most kidney stones form due to an imbalance between crystal-forming and crystal-inhibiting substances in the urine. The four main types are categorized by their chemical composition:
- Calcium Oxalate stones are the most frequent, accounting for up to 75% of all cases.
- Uric Acid stones are the second most common, often linked to high animal protein intake, gout, or metabolic conditions like diabetes.
- Struvite stones almost always form as a result of a chronic urinary tract infection.
- Cystine stones are caused by a rare, inherited genetic disorder called cystinuria.
The most common general risk factors for stone formation are chronic dehydration, which concentrates the urine, and certain dietary patterns. Diets high in sodium, excessive animal protein, and refined sugars all increase the amount of stone-forming chemicals the kidneys must filter.
Prevention and Monitoring Strategies
For individuals concerned about kidney stone risk, particularly those on testosterone therapy, focused actions can significantly reduce the likelihood of stone formation. The most impactful measure is increasing fluid intake to dilute the urine, aiming for a daily output of two to three quarts of clear urine. Lemon and lime juice, which contain citrate, can be added to water. Citrate is a natural inhibitor that helps prevent calcium stones and raises urinary pH to inhibit uric acid stone formation.
Dietary modifications should be tailored to the specific stone type, but general recommendations involve limiting high-sodium foods and reducing excessive animal protein intake. For those susceptible to calcium oxalate stones, it is beneficial to pair calcium-rich foods with oxalate-rich foods at the same meal. This strategy allows calcium to bind with oxalate in the gut before absorption, promoting excretion in the stool rather than the urine.
Monitoring for at-risk patients, especially those on TRT, should include regular blood tests for serum calcium and creatinine. A 24-hour urine collection may also be used to analyze the levels of stone-forming and stone-inhibiting substances.