Impact of temozolomide on gonadal function in patients with primary malignant brain tumors

J Oncol Pharm Pract. 2013 Dec;19(4):321-7. doi: 10.1177/1078155212469243. Epub 2013 Jan 4.

Abstract

Background: Cumulative exposure to alkylating agents may produce impaired reproductive function. Temozolomide is an alkylating agent approved for treating malignant gliomas.

Objective: A pilot study was undertaken to investigate the effects of temozolomide on semen integrity in men with newly diagnosed or recurrent malignant gliomas.

Methods: Eligible patients had no known fertility problems or impotence. Comprehensive semen analysis and serum sex hormones were obtained at baseline and following 3 and at least 6 months of temozolomide.

Results: Thirteen men were recruited. Mean age was 42 years (28-58). Three had recurrent and 10 newly diagnosed malignant glioma. Four were unable to ejaculate or were azoospermic at baseline. Four provided samples at baseline and after at least 6 months of temozolomide. Five were unable to complete the study. Two of four patients with paired baseline and 6-month samples received 6 months of standard monthly temozolomide. Two patients received standard radiation and concurrent temozolomide followed by adjuvant temozolomide. At 6 months, three of these four patients demonstrated low sperm motility (two low at baseline); three had abnormally low percent normal forms (one abnormal at baseline); two developed abnormally low sperm density. Sex hormone values were normal in all four patients at all time points.

Conclusion: Changes in semen analysis parameters following 6 months of temozolomide were observed. The small sample size precludes any firm conclusions regarding the importance and duration of these findings and their relation to temozolomide exposure. With validation in a larger study, these results may have important implications for counseling prior to initiation of temozolomide therapy in these patients.

Keywords: Malignant glioma; fertility; temozolomide.

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Combined Modality Therapy
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Follow-Up Studies
  • Glioma / pathology
  • Glioma / therapy
  • Gonadal Steroid Hormones / blood
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Pilot Projects
  • Prospective Studies
  • Semen / drug effects*
  • Sperm Motility / drug effects*
  • Temozolomide
  • Time Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Gonadal Steroid Hormones
  • Dacarbazine
  • Temozolomide