COSA:AYA cancer fertility preservation/Impact of cancer treatments on fertility/Male reproductive and hormonal functions

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Fertility preservation for AYAs diagnosed with cancer: Guidance for health professionals. > COSA:AYA cancer fertility preservation/Impact of cancer treatments on fertility/Male reproductive and hormonal functions

Impact of cancer treatments on male reproductive and hormonal functions

For young males diagnosed with cancer, infertility can result from:

  • the disease itself (best documented in patients with testicular cancer and Hodgkin lymphoma)
  • anatomic problems (eg retrograde ejaculation or anejaculation)
  • primary or secondary hormonal insufficiency
  • more frequently, damage or depletion of the germinal stem cells [1]


Future fertility may be impaired as a result of chemotherapy, particularly alkylating agents and cisplatin,[2] and testicular radiation.

Surgical treatments for some cancers can adversely impact transport of sperm and ejaculatory function.

The extent of damage to the spermatogenic system depends on:

  • age of the patient
  • type of drug/s used
  • dose and treatment regimen (eg combination therapies) and
  • administration (oral v intravenous) [3]

Temporary infertility (up to two years) can occur as a result of cytotoxic damage to the rapidly differentiating spermatogonia.[4]

Permanent infertility can result from irreparable damage to the spermatogenic stem cells.[5][6]

Effects of chemotherapy

Chemotherapy agents that are most likely to cause prolonged or permanent infertility in males are the alkylating agents including cyclophosphamide, chlorambucil, procarbazine and busulfan.[7][2]

In high doses, cisplatinum chemotherapy (Platinol) or bleomycin (Blenoxane, Bleomycin) can damage fertility.

The risk is increased if the patient receives two or more aklylating drugs, has higher doses of chemotherapy, or has a combination of chemotherapy and pelvic radiation.

Effects of radiation therapy

  • Direct radiation to the testes at doses of 1.2 Gy or more can cause infertility. The degree of risk is dose- and technique-dependent.[2]

Radiation to nearby organs can impair spermatogenesis if the testis is in or near the target area. If there is a mild dose of radiation to the testicles, fertility may drop but then recover over the following one to four years. There is no consensus as to the benefit of testicular shielding.

  • Total body irradiation generally causes permanent sterility in men.[8]
  • Cranial radiation may affect pituitary hormone production and release, impairing pubertal development and long-term reproductive function.[9] Exogenous hormone administration may restore hormonal functions.


Effects of surgery

  • Radical surgery to treat prostate or bladder cancer removes the prostate and seminal vesicles, preventing the transport of sperm cells.
  • Surgery for testicular or colon cancers may result in nerve damage, disrupting ejaculatory function.

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Table 3 summarises the effect of common cancer treatments on sperm production in males.

Table 3: Effect of cancer treatments on sperm production in males

Degree of risk Treatment Common usage
High risk: prolonged azoospermia after treatment Total body irradiation Bone marrow transplantation, Stem cell transplantation (BMT/SCT)
Testicular radiation dose > 2.5 Gy in men Testicular cancer, ALL, NHL
Testicular radiation dose ≥ 6 Gy in boys ALL, NHL, sarcoma, germ cell tumours
Protocols containing procarbazine: COPP, MOPP (83% risk) [10], MVPP (97% risk) [10], ChIVPP, ChIVPP/EVA, MOPP/ABVD, COPP/ABVD (62% risk) [10] Hodgkin lymphoma
Alkylating chemotherapy for transplantation conditioning (cyclophosphamide, busulfan, melphalan)(70% risk) [10] BMT/SCT
Any alkylating agent (eg, procarbazine, nitrogen mustard, cyclophosphamide) + TBI (80-90% risk) [10], pelvic radiation, or testicular radiation Testicular cancer, BMT/SCT, ALL, NHL, sarcoma, neuroblastoma, Hodgkin lymphoma
BEACOPP (67-80%) [10] Hodgkin lymphoma
Cyclophosphamide > 7.5 g/m2 Sarcoma, NHL, neuroblastoma, ALL
Cranial/brain radiation ≥ 40 Gy Brain tumour
Intermediate risk: prolonged azoospermia not common at standard dose BEP × 2-4 cycles Testicular cancer
Cumulative cisplatin dose < 400 mg/m2 Testicular cancer
Cumulative carboplatin dose ≤ 2 g/m2 Testicular cancer
Testicular radiation dose 1-6 Gy (as a result of scatter from abdominal/pelvic radiation) Wilms tumour, neuroblastoma
Low risk: temporary azoospermia after treatment Lower dose alkylating chemotherapy: ABVD (8% risk) [10], OEPA, NOVP, CHOP, COP Hodgkin lymphoma, NHL
Testicular radiation dose 0.2-0.7 Gy Testicular cancer
Very low/no risk: no effects on sperm production Testicular radiation dose < 0.2 Gy Multiple cancers
Interferon alfa Multiple cancers
Radioactive iodine Thyroid cancer
Unknown risk Irinotecan Colon cancer
Bevacizumab Colon, non–small-cell lung cancer
Cetuximab Colon, head and neck cancer
Erlotinib Non–small-cell lung, pancreatic cancer
Imatinib Chronic myeloid leukemia, GI stromal tumor

Source: Levine J, Canada A, Stern CJ. Fertility preservation in adolescents and young adults with cancer J Clin Oncol 2010 Nov 10;28(32):4831-41 [Available at http://www.ncbi.nlm.nih.gov/pubmed/20458029].

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References

  1. Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 2006 Jun 20;24(18):2917-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16651642.
  2. 2.0 2.1 2.2 Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 1998 Dec;27(4):927-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9922915.
  3. Fallat ME, Hutter J, American Academy of Pediatrics Committee on Bioethics, American Academy of Pediatrics Section on Hematology/Oncology, American Academy of Pediatrics Section on Surgery. Preservation of fertility in pediatric and adolescent patients with cancer. Pediatrics 2008 May;121(5):e1461-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18450888.
  4. Hart R. Preservation of fertility in adults and children diagnosed with cancer. BMJ 2008 Oct 27;337:a2045 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18955375.
  5. Shetty G, Meistrich ML. Hormonal approaches to preservation and restoration of male fertility after cancer treatment. J Natl Cancer Inst Monogr 2005;(34):36-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15784820.
  6. Feldschuh J, Brassel J, Durso N, Levine A. Successful sperm storage for 28 years. Fertil Steril 2005 Oct;84(4):1017 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16213859.
  7. Costabile RA.. The effects of cancer and cancer therapy on male reproductive function. J Urol 1993;149:1327-1330.
  8. Socié G, Salooja N, Cohen A, Rovelli A, Carreras E, Locasciulli A, et al. Nonmalignant late effects after allogeneic stem cell transplantation. Blood 2003 May 1;101(9):3373-85 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12511420.
  9. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989 Feb;70(262):145-60 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2594955.
  10. 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Leader A, Lishner M, Michaeli J, Revel A. Fertility considerations and preservation in haemato-oncology patients undergoing treatment. Br J Haematol 2011 May;153(3):291-308 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21391973.

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