Prevention of uterine bleeding after stem cell transplantation was attempted in 30 consecutive premenopausal women affected by hematological malignancies. This was with luteinizing hormone-releasing hormone (LHRH) leuprorelin acetate depot 3.75 mg administered subcutaneously at least 30 days before the conditioning regimen and then 28 days after the first dose. Complete prevention resulted in all but one patient (96.5%) during the phase of profound thrombocytopenia. No side-effects related to leuprorelin were observed. All patients developed amenorrhea after transplantation. Gonadal function was periodically assessed by means of luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol serum levels. Hormone levels were consistent with menopause in all patients. After transplantation, patients required hormone replacement with estroprogestinics or estrogens alone when indicated. Leuprorelin is highly effective in preventing uterine bleeding in premenopausal women undergoing stem cell transplantation and has an excellent toxicity profile and virtually no interface with hemostatic balance and hepatic function. The role of leuprorelin in gonadal protection is currently unclear and deserves further investigations.