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Objective: Retrograde ejaculation(RE)is an ejaculation disorder that can cause male infertility.It is defined as a pathological condition in which some or all semen is not emitted despite orgasm.The main cause of RE is believed to be decreased function of the bladder neck due to conditions such as diabetes,pelvic surgery,and drug resistance.Currently imipramine is the drug of choice for treatment of RE,but side effects such as drowsiness sometimes develop.In this controlled clinical study we evaluated the effectiveness and adverse effects of imipramine and amoxapine for treatment of RE.Methods: Twenty men were randomly assigned to one of two groups.We gave amoxapine to group Ⅰ and imipramine to group Ⅱ during the first 2-week period and examined adverse effects and semen volume.After a 1-week washout period,the drugs were switched for a second 2-week period.Mean age was 42.5 years(range,30-52).Disease duration was 3 months to 5 years(average,1.6 years).The main causes of RE were diabetes(n=13),surgery for rectal cancer(n=3),and retroperitoneal lymph node dissection for testicular cancer(n=l)(there is some overlapping);cause was unknown in 4 cases.Male infertility was the reason for consultation in 13 cases.The men were provided with a 2.5-cc syringe for self-measurement of semen volume during ejaculation.Results: In 9 cases,sperm was found in urine after orgasm.With amoxapine treatment,17(85.0%)men were able to ejaculate.Mild drowsiness was noted in 4 cases.With imipramine treatment,13(65.0%)men were able to ejaculate.Mild drowsiness was noted in 3 cases and severe drowsiness in 1 case.ED was observed in 5 patients,but erection hardness was greater than EHS3 after use of PDE5I.All men who reported semen emission with imipramine were also able to ejaculate while receiving amoxapine.Semen volume was significantly greater with amoxapine than with imipramine(P<0.001).The incidence of adverse effects was similar for amoxapine and imipramine.Amoxapine was effective for all men who had positive results with imipramine.Conclusions: In the treatment of RE,amoxapine was much more effective than imipramine,and equally safe.