High risk of infertility and long term gonadal damage in males treated with high dose cyolophosphamide for sarcoma during childhood

BACKGROUND, Therapy with alkylating agents, such as cyclophosphamide, can b e associated with irreversible gonadal toxicity in male survivors of adult cancer. To the authors's knowledge the effect of high dose therapy with cyc lophosphamide during childhood on adult testicular reproductive and endocri ne function has not been established. METHODS. Gonadal function was studied in 17 adult male survivors of childho od sarcomas treated with high dose pulse cyclophosphamide therapy as part o f a VAC (vincristine, actinomycin, and cyclophosphamide) or Adria-VAC (doxo rubicin, vincristine, actinomycin, and cyclophosphamide) chemotherapy regim en. Patients answered a questionnaire concerning sexual functioning and und erwent a comprehensive physical examination, semen analysis, and hormonal e valuation. RESULTS, Of the 17 males who underwent semen analysis, 10 (58.8%) had azoos permia, 5 (29.4%) had oligospermia, and only 2 (11.8%) were found to have a normal sperm count. All patients treated prior to the onset of puberty had an abnormal semen analysis. The 2 patients with normal sperm counts receiv ed the lowest doses of cyclophosphamide (< 7.5 g/m(2)). The baseline follic le-stimulating hormone level was elevated in only 10 of 14 patients with ab normal sperm counts (71.4%). Testosterone levels were normal in 15 of 16 pa tients (93.8%); however, the baseline luteinizing hormone (LH) level was el evated in 6 of 15 patients with normal testosterone levels (40%). Gonadotro pin-releasing hormone-stimulated LH levels were > 3 times that of baseline in 13 of /14 patients (92.9%), suggesting some degree of Leydig cell insuff iciency. CONCLUSIONS. The results of the current study show a high risk of gonadal d ysfunction in men exposed to cyclophosphamide during childhood as part of a VAC/Adria-VAC chemotherapy regimen. Exposure prior to puberty was not foun d to be protective, and the risk of infertility appeared to increase with h igher doses of therapy. To the authors' knowledge the clinical significance of impaired Leydig cell function beginning at a young age is unknown and m erits further study. (C) 2001 American Cancer Society.