Sirolimus‐Associated Infertility: Case Report and Literature Review of Possible Mechanisms

• Published in: American journal of transplantation Vol. 7; no. 10; pp. 2414 - 2421
• Main Authors: Deutsch, M. A., Kaczmarek, I., Huber, S., Schmauss, D., Beiras‐Fernandez, A., Schmoeckel, M., Ochsenkuehn, R., Meiser, B., Mueller‐Hoecker, J., Bruno Reichart, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell
• Subjects: Adult; Biological and medical sciences; Birth control; Gynecology. Andrology. Obstetrics; Heart transplantation; Heart-Lung Transplantation - immunology; Humans; immunosuppression; Immunosuppressive Agents - adverse effects; Infertility, Male - chemically induced; Leydig Cell Tumor - chemically induced; Leydig Cell Tumor - pathology; Leydig Cell Tumor - surgery; Male; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical sciences; Middle Aged; oligospermia; sirolimus; Sirolimus - adverse effects; Sterility. Assisted procreation; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; tertiality; Testicular Neoplasms - chemically induced; Testicular Neoplasms - pathology; Testicular Neoplasms - surgery; Tissue Donors; Antineoplastic agent; Heart; Sirolimus; Transplantation; Homotransplantation; Mechanism; Macrocycle; Surgery; Graft; Protein synthesis inhibitor; tertiality; Male genital diseases; Human; Heart transplantation; Lactone; Macrolide; Sterility; Semen disorders; Oligospermia; Case study; Antibiotic; Immunosuppression; Treatment; Circulatory system; Immunosuppressive agent; Antibacterial agent; Bibliographic review
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2007.01929.x

The mammalian‐target‐of‐rapamycin/mTOR‐inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters. Herein, we report on a case of sirolimus‐associated infertility in a young male heart‐lung transplant recipient and provide a detailed synopsis of potential mechanisms by which sirolimus may negatively influence spermatogenesis. Testicular immunohistochemistry, the course of sex hormone and sperm quality parameters of our patient support the hypothesis that mTOR might act as an important key regulator in the reproductive system. Fortunately, due to withdrawal of sirolimus as part of the maintenance, immunosuppression improved sperm quality and sex hormone parameters could be observed. Recently, these improvements even resulted in a spontaneous pregnancy of the patient's wife more than 1 year after the drug was withdrawn. In our view, oligospermia as a possible and at least partly reversible side‐effect of mTOR inhibitors has to be taken into consideration, particularly, when administrated to young male patients. The authors delineate a case of sirolimus‐associated infertility and provide a detailed synopsis of potential molecular mechanisms by which the mTOR‐inhibitor sirolimus may negatively influence spermatogenesis.