Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine...
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![Page 1: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/1.jpg)
Testicular Function after Cytotoxic Therapy
International Symposium on Reproductive MedicineIstanbulJune 4-6, 2010
Herman Tournaye, M.D. Ph.D.Centre for Reproductive Medicine Brussels
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outline of the lecture
• the testis: a brief introduction
• effects on the endocrine function
• effects on the exocrine function
• take-home messages
![Page 3: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/3.jpg)
ww
w.inquisitr.com
/wp-content/conflict.jpg
The speaker declares no conflict of interest with
the topic presented in this lecture
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outline of the lecture
• the testis: a brief introduction
• effects on the endocrine function
• effects on the exocrine function
• take-home messages
![Page 5: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/5.jpg)
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differentiation Clermont 1976Ehmcke et al. 2005
Ad/Ap-model of stem cell renewal
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http://www.enlarged-prostate-treatment.info
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outline of the lecture
• the testis: a brief introduction
• effects on the endocrine function
• effects on the exocrine function
• take-home messages
![Page 12: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/12.jpg)
• less sensitive than germinal epithelium:
slighly elevated LHmild testosterone deficiency to normal(Shalet et al. 1999; Chatterjee et al. 1994)
• more prone to irradiation damage in pre-pubertal life (Shalet et al. 1989)
and if radiation dose >2400 cGy
Leydig cell function after CT / RT
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• some of these men with subnormal testosterone levels show reduced bone density(Howell et al. 2000)
• blinded placebo controlled RCT shows no benefit/ indication for androgens(Howell et al. 2001)
Leydig cell function after CT / RT
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outline of the lecture
• the testis: a brief introduction
• effects on the endocrine function
• effects on the exocrine function
• take-home messages
![Page 15: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/15.jpg)
www.uh.edu/~tgill2/image016.jpg
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Sharpe et al. 2003
Sertoli cell function after CT / RT
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• controversy on action on Sertoli cells
• unaffected when not replicating(Orth et al. 1988; Jégou et al. 1993)
• indirect effect on FSH through loss of germ cells (Jégou et al. 1993)
Sertoli cell function after CT / RT
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Sertoli cell function after CT / RT
• CT @ age 13• testisbiopsy @ age 31
• unexpected expression ofcytokeratin-18 in 13% oftubuli (prepubertal marker)
• cytotoxic effect ?
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Effect of single dose RT
Rowley et al. 1974, Howell & Shalet 2005
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• > because of scattered irradiation
• increased gonadotoxicity vs single-dose
• 1.2 Gy = treshold for permanent testicular damage without recovery in most patients
• TBI (>10 Gy): ≤ 1% fatherhood (Sanders et al.)
Effect of fractionated RT
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• interference with DNA & RNA synthesis(antimetabolites e.g. fluorouracil)
• inhibition of protein synthesis (alkylating e.g. cyclophosphamide,busulfan)
• interference with microtubule function(plant alkaloids e.g. vincristine, taxanes)
Effect of CT
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“Fertility-friendly chemotherapy”
• no chemotherapy guarantees 100% fertility
• oligozoospermia ≠ fertility
• risk aneuploidy and mutagenesis
• you never know the final treatment course
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A survey among patients
• 904 male cancer patients 14-40 yrs old
• Texas and Ohio
• 27% response rate (n=201, 8% refused survey)
• want children after cure? 51% overall
77% of childless
• informed about infertility?: only 60%
• informed about banking semen?: only 51%
• banked semen?: 24% (27% of childless)
Schover et al., J. Clin. Oncol. 2002
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The myth of the ‘testicular quiescence’
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Induction of ‘testicular quiescence’
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Testis is ‘quietly active’ rather than ‘truly quiescent’
Kelnar et al. H
um. R
eprod. 2002
Control marmoset GnRHa-treated marmoset
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>80% risk for sterility after cytostatic treatment
whole body irradiation
conditioning for bone-marrow transplantation
Hodgkin treated with alkylating agents
metastatic Ewing’s sarcoma
metastatic soft-tissue sarcoma
testicular radiotherapy
Wallace et al. Lancet Oncol. 2005
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Distribution Children’s Cancer Research Group UK
Anderson et al. Hum. Reprod. 2008
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Anderson et al. Hum. Reprod. 2008
risk for sterility after cytostatic treatment
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outline of the lecture
• the testis: a brief introduction
• effects on the endocrine function
• effects on the exocrine function
• take-home messages
![Page 39: Testicular Function after Cytotoxic Therapy International Symposium on Reproductive Medicine Istanbul June 4-6, 2010 Herman Tournaye, M.D. Ph.D. Centre.](https://reader030.fdocuments.in/reader030/viewer/2022032707/56649e395503460f94b2a346/html5/thumbnails/39.jpg)
Leydig cell deficiency
• clinically not important for most men
• no indication for routine substitution
• 'vigilant' management
Take-home messages
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Spermatogenesis
• non-proliferative Sertoli cells are resistant
• no quiescent prepubertal stage
• all patients need proper counseling
• cryobanking in adults and children
Take-home messages
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