title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Wake Forest School of Medicine, NC, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Strowd
authors.forename: R
authors.initials: R
authors.lastname: Blackwood
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Harmon
authors.forename: J
authors.initials: J
authors.lastname: Lovato
authors.forename: T
authors.initials: T
authors.lastname: Yalcinkaya
authors.forename: G
authors.initials: G
authors.lastname: Lesser
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology / Q000628:therapy; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010865:Pilot Projects; D011446:Prospective Studies; D012661:Semen / Q000187:drug effects*; D013081:Sperm Motility / Q000187:drug effects*; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012739:Gonadal Steroid Hormones; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Malignant glioma; fertility; temozolomide