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Sirolimus Impairs Improvement of the Gonadal Function after Renal Transplantation

2005; Elsevier BV; Volume: 5; Issue: 1 Linguagem: Inglês

10.1111/j.1600-6143.2005.00604.x

1600-6143

Vincenzo Tondolo, Franco Citterio, Nicola Panocchia, G Nanni, M Castagneto,

Pharmacological Effects and Toxicity Studies

Ingo Kaczmarek (1Kaczmarek I Sirolimus impairs gonadal function in heart transplant recipients..Am J Transplant. 2004; 4: 1084-1088Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar) found in heart transplant recipients (HTX) that sirolimus (SRL) may significantly decrease testosterone, with a significant increase in FSH and LH levels. These changes correlated positively with the duration of treatment and with SRL trough levels. We looked at testosterone levels in a group of renal transplant recipients (KTX) receiving SRL. HTXs and KTXs have different baseline pathologies, but after transplantation they receive the same immunosuppressive drugs, although with different doses and combinations. Chronic renal failure patients commonly have disturbances of the hypothalamic-pituitary-gonadal function frequently resulting in sexual dysfunctions. Low testosterone, high FSH and high LH levels are frequently found in hemodialysis patients. Sexual dysfunction associated with uremia may significantly improve or normalize after successful renal transplantation. However, many pre- and post-transplant factors influence the hormonal profile, and among these factors the immunosuppressive drugs certainly play a role. We performed a comparative cross-sectional study of sexual hormonal profile among 59 males KTX with stable renal function, selected in the outpatient clinic. Criteria for selection were first-cadaveric KTX, creatinine < 2.5 mg/dL and assumption of no drug known to interfere with the hormonal status. Testosterone, FSH and LH levels were measured in plasma and related to the principal agent used in the immunosuppressive combination. Three groups were identified: (1) combination I (CI), 15 patients, receiving cal-cineurine inhibitors (cyclosporine or tacrolimus) without SRL; (2) combination II (SRL), 15 patients, receiving SRL without CI; (3) combination III (CI + SRL), 29 patients, receiving SRL + CI. All patients were on the same maintenance steroid therapy. The mean age of the entire cohort of KTX studied was 48 ± 10 years; time after transplantation was 56 ± 55 months and serum creatinine was 1.9 ± 0.7 mg/dL. The three groups were similar for the age distribution and for the renal function. Testosterone levels were significantly lower in patients receiving SRL without CI, versus patients receiving CI (testosterone: SRL 3.12 ± 1.23 vs CI 4.39 ± 1.53 ng/mL; p < 00197). Patients receiving SRL + CI had intermediate testosterone values (testosterone: SRL + CI 3.97 ± 1.98 ng/mL). In the SRL group, FSH and LH were also higher, but differences were not statistically significant, perhaps due to the small number of patients. However, median FSH values in the SRL group were 13 mUI/mL, above the normal range (normal range: 2.5–11 mUI/mL), while in the SRL + CI and CI cohort, median FSH was within the normal range (8 and 6 mUI/mL, respectively). In conclusion, our data in KTX support the finding in HTX, although pathways are different. In HTX, patients on SRL had their testosterone levels reduced with the duration of treatment, in KTX we observed in patients on SRL the poor improvement of testosterone levels after transplantation. Starting from different positions the effects of rapamycine were the same: impairment of the gonadal function. These data support the need for further prospective, randomized studies to evaluate sexual function in transplant recipients on rapamycine.