Literature DB >> 19774480

Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus.

Yousef Boobes1, Bassam Bernieh, Hussein Saadi, M Raafat Al Hakim, Samra Abouchacra.   

Abstract

Sirolimus is an immunosupressor of the mammalian target of rapamycin inhibitors (mTOR-I) group. Recent studies have emphasized a potential impact of sirolimus on male gonadal function. We report our clinical experience with sirolimus-induced gonadal dysfunction and infertility in both male and female kidney transplant patients. Of the 170 kidney transplant patients, nine (5.3%) patients (six males and three females) were receiving sirolimus. Follow-up data for two male patients were not available. The one unmarried female patient developed amenorrhea post-transplantation and had resumption of her menstrual cycles after discontinuation of sirolimus. The remaining six married patients (four males and two females), who all had fathered or conceived children in the pre-transplantation period, developed gonadal dysfunction and infertility on average 5-12 months after transplantation. Sirolimus was discontinued in all four male patients with full recovery of the oligo/azospermia and restoration of fertility. Both married female patients developed amenorrhea post-transplantation. Sirolimus was discontinued in one female patient with resumption of her menstrual cycles. In this small population of patients treated with sirolimus, the prevalence rate of reversible gonadal dysfunction and infertility was significant in both males and females. Infertility secondary to sirolimus is under-diagnosed and should be studied further.

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Year:  2009        PMID: 19774480     DOI: 10.1007/s11255-009-9644-8

Source DB:  PubMed          Journal:  Int Urol Nephrol        ISSN: 0301-1623            Impact factor:   2.370


  16 in total

1.  A randomized, double-blind, placebo-controlled study of the safety, tolerance, and preliminary pharmacokinetics of ascending single doses of orally administered sirolimus (rapamycin) in stable renal transplant recipients.

Authors:  E M Johnson; J Zimmerman; K Duderstadt; J Chambers; A L Sorenson; D K Granger; P S Almond; J p Fryer; J R Leventhal; J Scarola; A J Matas; D M Canafax
Journal:  Transplant Proc       Date:  1996-04       Impact factor: 1.066

2.  Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses.

Authors:  H Kissel; I Timokhina; M P Hardy; G Rothschild; Y Tajima; V Soares; M Angeles; S R Whitlow; K Manova; P Besmer
Journal:  EMBO J       Date:  2000-03-15       Impact factor: 11.598

3.  A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts.

Authors:  A S MacDonald
Journal:  Transplantation       Date:  2001-01-27       Impact factor: 4.939

4.  Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia.

Authors:  L X Feng; N Ravindranath; M Dym
Journal:  J Biol Chem       Date:  2000-08-18       Impact factor: 5.157

5.  The effect of sirolimus on sex hormone levels of male renal transplant recipients.

Authors:  Suji Lee; Maria Coco; Stuart M Greenstein; Richard S Schechner; Vivian A Tellis; Daniel G Glicklich
Journal:  Clin Transplant       Date:  2005-04       Impact factor: 2.863

6.  Azoospermia in a renal transplant recipient during sirolimus (rapamycin) treatment.

Authors:  J Skrzypek; W Krause
Journal:  Andrologia       Date:  2007-10       Impact factor: 2.775

7.  Sirolimus impairs gonadal function in heart transplant recipients.

Authors:  Ingo Kaczmarek; Jan Groetzner; Ioannis Adamidis; Peter Landwehr; Markus Mueller; Michael Vogeser; Michael Gerstorfer; Peter Uberfuhr; Bruno Meiser; Bruno Reichart
Journal:  Am J Transplant       Date:  2004-07       Impact factor: 8.086

8.  Testosterone concentrations and sirolimus in male renal transplant patients.

Authors:  Lutz Fritsche; Klemens Budde; Duska Dragun; Gunilla Einecke; Fritz Diekmann; Hans-Hellmut Neumayer
Journal:  Am J Transplant       Date:  2004-01       Impact factor: 8.086

9.  Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune, rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis.

Authors:  Amir Tejani; Steven Alexander; Robert Ettenger; Gary Lerner; James Zimmerman; Edward Kohaut; David M Briscoe
Journal:  Pediatr Transplant       Date:  2004-04

10.  Sirolimus-associated infertility: case report and literature review of possible mechanisms.

Authors:  M A Deutsch; I Kaczmarek; S Huber; D Schmauss; A Beiras-Fernandez; M Schmoeckel; R Ochsenkuehn; B Meiser; J Mueller-Hoecker; B Reichart; B Bruno Reichart
Journal:  Am J Transplant       Date:  2007-10       Impact factor: 8.086

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  18 in total

1.  The rapamycin analog Everolimus reversibly impairs male germ cell differentiation and fertility in the mouse†.

Authors:  Oleksandr Kirsanov; Randall H Renegar; Jonathan T Busada; Nicholas D Serra; Ellen V Harrington; Taylor A Johnson; Christopher B Geyer
Journal:  Biol Reprod       Date:  2020-10-29       Impact factor: 4.285

2.  mTOR inhibitor sirolimus negatively impacts in vitro fertilization outcomes.

Authors:  Kaitlyn Wald; Hakan Cakmak; Martha Noel
Journal:  J Assist Reprod Genet       Date:  2019-03-25       Impact factor: 3.412

3.  mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy.

Authors:  Kara N Goldman; Devon Chenette; Rezina Arju; Francesca E Duncan; David L Keefe; Jamie A Grifo; Robert J Schneider
Journal:  Proc Natl Acad Sci U S A       Date:  2017-03-07       Impact factor: 11.205

4.  Tacrolimus and sirolimus induce reproductive abnormalities in female rats.

Authors:  Vijay Shivaswamy; Luann Ochsner; Dulce Maroni; Cheng Wang; Joel Passer; Cara E Clure; Frederick G Hamel; John S Davis; Jennifer Larsen
Journal:  Transplantation       Date:  2011-06-27       Impact factor: 4.939

Review 5.  Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Authors:  Tito T Jesus; Pedro F Oliveira; Mário Sousa; C Yan Cheng; Marco G Alves
Journal:  Crit Rev Biochem Mol Biol       Date:  2017-01-26       Impact factor: 8.250

6.  Long-term side effects of treatment with mTOR inhibitors in children after renal transplantation.

Authors:  Birgitta Kranz; Anne-Margret Wingen; Udo Vester; Jens König; Peter F Hoyer
Journal:  Pediatr Nephrol       Date:  2013-04-13       Impact factor: 3.714

7.  Mammalian target of rapamycin complex 1 (mTORC1) Is required for mouse spermatogonial differentiation in vivo.

Authors:  Jonathan T Busada; Bryan A Niedenberger; Ellen K Velte; Brett D Keiper; Christopher B Geyer
Journal:  Dev Biol       Date:  2015-08-05       Impact factor: 3.582

8.  HCG-mediated activation of mTORC1 signaling plays a crucial role in steroidogenesis in human granulosa lutein cells.

Authors:  Molly B Moravek; Min Shang; Bindu Menon; Kmj Menon
Journal:  Endocrine       Date:  2016-08-08       Impact factor: 3.633

9.  Testosterone in renal transplant patients: effect on body composition and clinical parameters.

Authors:  Danilo Lofaro; Anna Perri; Antonio Aversa; Benedetta Aquino; Martina Bonofiglio; Antonella La Russa; Maria Giovanna Settino; Francesca Leone; Alessandro Ilacqua; Filomena Armentano; Donatella Vizza; Simona Lupinacci; Giuseppina Toteda; Renzo Bonofiglio
Journal:  J Nephrol       Date:  2018-07-17       Impact factor: 3.902

10.  Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial.

Authors:  Matthias Braun; James Young; Cäcilia S Reiner; Diane Poster; Fabienne Krauer; Andreas D Kistler; Paulus Kristanto; Xueqi Wang; Yang Liu; Johannes Loffing; Gustav Andreisek; Arnold von Eckardstein; Oliver Senn; Rudolf P Wüthrich; Andreas L Serra
Journal:  PLoS One       Date:  2012-10-10       Impact factor: 3.240

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