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

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.