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Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: an overview

Huyghe, Eric, Zairi, Anas, Nohra, Joe, Kamar, Nassim, Plante, Pierre, Rostaing, Lionel·2007·Transplant International
DOI 10.1111/j.1432-2277.2006.00423.x
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Abstract

The immunosuppressive agents target of rapamycin inhibitors (TOR-I) (sirolimus, and everolimus) have been widely used in kidney transplantation for >10 years. Up to 40% of men receiving a kidney transplant are younger than 50, and fertility as well as erectile function are major concerns. In this review, we provide a synopsis of past studies focusing on gonadal function in men treated with TOR-I, mainly sirolimus, to establish what impact they have on male gonads, and which pathophysiological pathways are involved. A PubMed search for the years 1990-2006 selected articles that focused on the gonadal impact of TOR-I. Primary outcome measures were testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels. Secondary outcome measures were sexual function, fertility status and sperm parameters. Treatment with TOR-I results in a decrease in testosterone level, and an opposite increase in LH. Moreover, spermatogenesis seems to be disrupted by TOR-I and FSH levels are increased. Sirolimus and everolimus inhibit the activity of mammalian targets of rapamycin, a serine/threonine kinase involved in numerous cell-growth processes. Molecular mechanisms of action of TOR-I on the testis involve inhibition of a stem cell factor/c-kit-dependant process in spermatogonia. Preliminary results appear to show that TOR-I treatment has deleterious actions on the testis and impairs gonadal function after renal transplantation, but the impact of these effects are unknown.

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  • Another side effect of doses of rapamycin that extend lifespan in mice is testicular degeneration, and reduced male fertility has been observed in humans treated with rapalogs.

    “Another side effect of doses of rapamycin that extend lifespan in mice is testicular degeneration 25,144, and reduced male fertility has been observed in humans treated with rapalogs 145,146.”

    From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [146]

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Metadata

Authors
Huyghe, E., Zairi, A., Nohra, J., Kamar, N., Plante, P., & Rostaing, L.
Venue
Transplant International
Publisher
Frontiers Media SA
Published
2007-04
Volume
20
Issue
4
Pages
305-311
ISSN
  • 0934-0874
  • 1432-2277
DOI
10.1111/j.1432-2277.2006.00423.x
Cited by
159
References
0
Language
en
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3075 d)

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