Sirolimus Impairs Gonadal Function in Heart Transplant Recipients

The impact of sirolimus on hormone levels involved in the hypothalamus‐pituitary‐gonad axis in male heart transplant recipients was investigated. A pair‐matched analysis with 132 male heart transplant recipients on either sirolimus based‐ or calcineurin inhibitor‐based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone‐binding globulin (SHBG) and free androgen index (FAI). Mean testosterone was 3.86 ± 1.41 ng/mL in the sirolimus group and 4.55 ± 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 ± 11.19 mlU/mL in the sirolimus patients and 6.2 ± 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 ± 18.4 mlU/mL vs. 7.32 ± 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01). Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough‐level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.