A Retrospective Study of the Relationship Between Testicular Damage and Urinary Creatine Excretion: Possible Markers of Testicular Toxicity Induced by Drugs

Abstract

ObjectivesCreatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with high and fluctuating energy demands. Total creatine content of the rat testis is high compared to all other tissues except skeletal muscle and creatine excretion in rat urine has been shown to increase following testicular damage caused by toxicants. Because the use of biomarkers in toxicology is becoming increasingly important, we investigated whether urinary creatine might be a useful marker for testicular damage in human.MethodsIn a retrospective study, the records of 22 male patients with urological malignancies treated with cisplatin, leuprorelin or goserelin at 4‐week intervals between October 2005 and October 2015 were evaluated. Urinary creatine and serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels were assessed in all patients. Single‐voided urine samples were collected to determine urinary creatine‐to‐creatinine ratios. Blood sample collection was done in the morning when serum testosterone levels are around their peak: such morning time sampling for testosterone measurements is recommended in the clinical setting and routinely used in epidemiological studies.ResultsSeven patients with urothelial carcinoma treated with cisplatin based chemotherapy (mean age, 64.1 years) showed no significant changes in urine creatine/creatinine ratio during treatment and had a significant increase in FSH and LH levels and a significant decrease in testosterone levels compared to those at baseline. Similarly, no significant changes in urine creatine/creatinine ratio occurred in patients with prostatic carcinoma treated with leuprorelin (n=8; mean age, 70.0 years) or goserelin (n=7; mean age, 70.4 years), both of whom had castrate levels of testosterone (≤0.5 ng/mL) and suppressed levels of FSH and LH during treatment.ConclusionsOur data demonstrate that testicular damage could not be detected by urinary creatine in patients treated with drugs showing testicular toxicity. Two major testicular functions, i.e., the production of testosterone and formation of haploid germ cells, are generally considered to be regulated by pituitary gonadotrophins, with LH acting on the testosterone‐producing Leydig cells located in the interstitium and FSH affecting Sertoli cells in the seminiferous tubules. Thus, our hormonal data may indicate the presence of cisplatin‐induced Sertoli cell dysfunction and inhibition of Leydig cell function by LH‐RH analogues.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.