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

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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.

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