Sirolimus Impairs Gonadal Function in Heart Transplant Recipients

Abstract

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.

A prospective study in male recipients of kidney transplantation reveals divergent patterns for inhibin B and testosterone secretions

“…It has been previously reported that sirolimus may impair testicular function [32, 33] and male heart transplant recipients treated with sirolimus exhibited a significant increase in FSH levels and a drop of testosterone level [34]. In our study, the TAC plus mTORi regimen did not affect testosterone levels, but reduced those of inhibin B although the decrease was not significant ( p  = 0.093) (with the small number of patients within the subgroup as an acceptable reason).…”

Temsirolimus in the treatment of mantle cell lymphoma

“…The most frequent disorders reported are erectile dysfunction and libido disorders in men, whereas women can present with dyspareunia, vaginal dryness and vulvovaginitis [38,39]. Impaired gonadal dysfunction with decreased testosterone production has been described in male transplant patients receiving sirolimus [40,41]. Impaired gonadal dysfunction with decreased testosterone production has been described in male transplant patients receiving sirolimus [40,41].…”

Free Androgen Index Is Superior to Total Testosterone for Short-Term Assessment of the Gonadal Axis after Renal Transplantation

“…The immunosuppressant sirolimus leads to an impairment of the HPG axis [6, 14] but sirolimus was not used in our study. Therapy with different calcineurin inhibitors, cyclosporine A or tacrolimus, do not seem to relevantly influence these hormonal parameters [1, 3, 24].…”

“…Two recent studies, focusing on the effect of the immunosuppressant sirolimus on the HPG axis in cardiac and renal transplant recipients, used measurements of SHBG and total testosterone with divergent results of the total testosterone and free testosterone fraction [14, 15]. In both studies sirolimus was associated with decreased total testosterone concentrations but not with the free fraction of testosterone.…”