title: 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.
authors.affiliation: Department of Cardiac Surgery, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany. ingo.kaczmarek@med.uni-muenchen.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
authors.forename: Jan
authors.initials: J
authors.lastname: Groetzner
authors.forename: Ioannis
authors.initials: I
authors.lastname: Adamidis
authors.forename: Peter
authors.initials: P
authors.lastname: Landwehr
authors.forename: Markus
authors.initials: M
authors.lastname: Mueller
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.forename: Michael
authors.initials: M
authors.lastname: Gerstorfer
authors.forename: Peter
authors.initials: P
authors.lastname: Uberfuhr
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000728:Androgens / Q000378:metabolism; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005500:Follow-Up Studies; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006066:Gonads / Q000502:physiology*; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D000728:Androgens; D065095:Calcineurin Inhibitors; D012739:Gonadal Steroid Hormones; D007166:Immunosuppressive Agents; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003404:Creatinine; D020123:Sirolimus