Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment

Infertility after treatment of patients with Hodgkin's disease (HD) is cons idered as a side effect of alkylating agent containing chemotherapy regimen s. To investigate whether gonadal failure is related primarily to the toxic effect of chemotherapy or rather to the disease itself, we investigated th e fertility status before the onset of treatment. Patients and Methods: Semen quality and hormonal status were evaluated in 1 58 patients with first diagnosis of HD enrolled into trials of the German H odgkin Lymphoma Study Group (GHSG). The median age of the patients was 28 y ears (range 16-52). Twenty patients (13%) were classified as early stage HD , 63 patients (40%) as intermediate stage, and 75 patients (47%) as advance d stage according GHSG grading. Sixty-seven patients (42%) showed systemic symptoms. Semen analysis was performed according to WHO guidelines. Follicl e-stimulating hormone (FSH) and luteinising hormone (LH) plasma levels were measured by specific double-antibody radio-immune-assay (RIA) methods. Results: Prior to treatment, severe damage of fertility, i.e., azoospermia and oligoasthenoteratospermia (OAT-syndrome) was found in 13 (8%) and 20 pa tients (13%), respectively. Thirty-eight patients (24%) had single, i.e., o ligo-(O), astheno-(A) or teratospermia-(T), and 40 patients (26%) showed co mbined damages, i.e., OA, OT or AT. In 47 patients (30%) a normal sperm cou nt was found. Thus, 111 patients (70%) showed semen abnormalities before th e onset of treatment. In a multivariate analysis elevated ESR (P < 0.003) a nd advanced stage of disease (P < 0.01) could be distinguished as prognosti c factors for severe damage of fertility. No correlation was found between pre-therapeutic gonadotropine levels and fertility status. Conclusion: Patients with HD have an increased risk for inadequate semen qu ality even prior to treatment. Infertility is more frequent in patients wit h elevated ESR and advanced stage of disease. This association demonstrates the predominant influence of the disease on fertility. Assuming HD is the major initial cause for infertility efforts should be made to identify new non-gonadal toxic chemotherapies to be able to regain fertility after effec tive therapy. Further investigations have to be performed to clarify mechan isms inducing fertility defects in patients with HD.