Use of testosterone to prevent cyclophosphamide-induced azoospermia

Ann Intern Med. 1997 Feb 15;126(4):292-5. doi: 10.7326/0003-4819-126-4-199702150-00005.


Background: Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations.

Objective: To study the possible protective effect of testosterone used to inhibit germinal cell activity in men who are receiving cyclophosphamide.

Design: Randomized, clinical trial.

Setting: University medical center.

Patients: 15 patients with the nephrotic syndrome who were treated with cyclophosphamide for 6 to 8 months.

Intervention: Five patients received daily oral cyclophosphamide, five received cyclophosphamide in monthly bolus injections, and five received monthly intravenous boluses of cyclophosphamide plus testosterone (100 mg intramuscularly every 15 days).

Measurements: Sperm counts, serum follicle-stimulating hormone levels, and serum luteinizing hormone levels were measured before, during, and after treatment with cyclophosphamide alone or cyclophosphamide plus testosterone.

Results: The 10 patients who did not receive testosterone became azoospermic during cyclophosphamide therapy. In only 1 of the 10 patients did the sperm count return to normal 6 months after discontinuation of therapy. Follicle-stimulating hormone levels were elevated in these patients (mean +/- SE, 19.20 +/- 1.28 IU/L in patients receiving oral cyclophosphamide and 16.04 +/- 2.22 IU/L in patients receiving intravenous cyclophosphamide alone). All 5 patients who received testosterone became azoospermic or severely oligospermic during treatment but had a normal sperm count 6 months after the discontinuation of therapy. In these patients, the mean sperm count was 45.78 +/- 3.89 x 10(6)/mL and follicle-stimulating hormone levels were normal (5.08 +/- 0.56 IU/L).

Conclusion: Testosterone given to men before and during an 8-month cycle of cyclophosphamide therapy for the nephrotic syndrome may preserve fertility.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Drug Administration Schedule
  • Follicle Stimulating Hormone / blood
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Luteinizing Hormone / blood
  • Male
  • Nephrotic Syndrome / drug therapy
  • Oligospermia / blood
  • Oligospermia / chemically induced*
  • Oligospermia / prevention & control*
  • Prospective Studies
  • Sperm Count / drug effects
  • Testosterone / therapeutic use*


  • Immunosuppressive Agents
  • Testosterone
  • Cyclophosphamide
  • Luteinizing Hormone
  • Follicle Stimulating Hormone