Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas

Cancer. 1992 Dec 1;70(11):2703-12. doi: 10.1002/1097-0142(19921201)70:11<2703::aid-cncr2820701123>;2-x.


Background: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men.

Methods: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy.

Results: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2.

Conclusions: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Dacarbazine / adverse effects
  • Doxorubicin / adverse effects
  • Humans
  • Male
  • Oligospermia / chemically induced
  • Sarcoma / drug therapy*
  • Sarcoma, Ewing / drug therapy*
  • Soft Tissue Neoplasms / drug therapy*
  • Sperm Count / drug effects*
  • Time Factors
  • Vincristine / adverse effects


  • Vincristine
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • CYVADIC protocol
  • CyADIC regimen