Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men. Alkylating agents, such as cyclophosphamide and procarbazine, are the most common agents implicated. The majority of men receiving procarbazine-containing regimens for the treatment of lymphomas are rendered permanently infertile. Treatment with ABVD has a significant advantage in terms of testicular function, with a return to normal fertility in the majority of patients. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with spermatogenesis recovery in approx 50% after 2 yr and 80% after 5 yr. There is also evidence of chemotherapy-induced Leydig cell impairment in a proportion of these men, although this is of no clinical significance in the majority of patients. The germinal epithelium is sensitive to radiation-induced damage, with changes to spermatogo-nia after as little as 0.1 Gy and permanent infertility after fractionated doses of 2 Gy and higher, whereas clinically significant Leydig cell impairment occurs rarely with doses of less than 20 Gy. These effects are summarized in Table 2.
All men should be counseled regarding the possible effects of treatment on testicular function, and sperm banking should be offered to all patients who are undergoing potentially sterilizing therapy. Hormonal manipulation to enhance spermatogenesis recovery and cryopreservation of testicular tissue are possible future methods of preserving fertility but are currently unproven. Regular semen analyses should be offered to men after cytotoxic treatment to allow appropriate family planning. Measurement of testosterone and LH are appropriate for men with symptoms consistent with testosterone deficiency who have received significant doses of irradiation to the testes, pro-carbazine-containing chemotherapy, or high-dose chemotherapy. Mild LH elevations, accompanied by testosterone levels in the normal range (the most common abnormality), do not require treatment, but patients with subnormal testosterone levels and markedly elevated LH levels may benefit from androgen replacement.
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