International Journal of Impotence Research (2013) 26, 83–86 & 2013 Macmillan Publishers Limited All rights reserved 0955-9930/13 www.nature.com/ijir

ORIGINAL ARTICLE Hemospermia: long-term outcome in 165 patients

J Zargooshi, S Nourizad, S Vaziri, MR Nikbakht, A Almasi, K Ghadiri, S Bidhendi, H Khazaie, H Motaee, S Malek-Khosravi, N Farshchian, M Rezaei, Z Rahimi, R Khalili, L Yazdaani, K Najafinia and M Hatam

Long-term course of hemospermia has not been addressed in the sexual medicine literature. We report our 15 years’ experience. From 1997 to 2012, 165 patients presented with hemospermia. Mean age was 38 years. Mean follow-up was 83 months. Laboratory evaluation and testis and transabdominal ultrasonography was done in all. Since 2008, all sonographies were done by the first author. One patient had urinary , one had bladder tumor and three had benign lesions at verumontanum. One patient had bilateral partial ejaculatory duct obstruction by stones. All six patients had persistent, frequently recurring or high-volume hemospermia. All pathologies were found in young patients. In the remaining 159 patients (96%), empiric treatment was given with a fluoroquinolone (Ciprofloxacin) plus an nonsteroidal anti-inflammatory drug (Celecoxib). In our 15 years of follow-up, no patient later developed life-threatening disease. Diagnostic evaluation of hemospermia is not worthwhile in the absolute majority of cases. Advanced age makes no difference. Only high-risk patients need to be evaluated. The vast majority of cases may be safely and effectively treated with empiric therapy. Almost all patients do well in long term.

International Journal of Impotence Research (2013) 26, 83–86; doi:10.1038/ijir.2013.40; published online 5 December 2013 Keywords: genital diseases; hemorrhage; hemospermia; male;

INTRODUCTION provider of specialized sexual medicine health care and the sole Hemospermia () is the presence of blood in the destination for the referral cases of sexual medicine in the Kermanshah province and the neighboring five provinces of western Iran (Ilam, Loristan, semen. Despite being a source of considerable anxiety in patients, Kurdistan, Khuzestan and Hamadan). From the first day of launching the hemospermia and its long-term clinical course has not been clinic, we have recorded the patients’ full clinical and laboratory data into adequately addressed in the sexual medicine literature. Reported our electronic information storage and retrieval system, the UNESCO’s experience in various countries shows that hemospermia is rarely database management system CDS/ISIS. For the purpose of this article, a associated with any significant urologic pathology. In India,1 among search of the chief complaint field of our electronic data set was done for 35 patients with hemospermia, infection was the most common the keyword hemospermia. After saving the search results, electronic files cause (40%). In Taiwan,2 no cancer was found in 40 of the identified patients were reviewed and relevant information was patients with hemospermia. In Korea,3 again, no extracted and summarized. Based on our database search, from 2 January found in 17 patients with hemospermia. In Italy,4 no malignant 1997 to 15 March 2012, 165 patients presented to us with the chief complaint of hemospermia of 1 day to 2 years duration. During the same disease was demonstrated in 90 patients with hemospermia. In 5 period, we have seen 36 252 patients with urologic complaints. Thus, Japan, too, no malignant lesions were found in the prostate or considering our very large case load, our hemospermia cases are of 46 patients with hemospermia. In these studies, representative of the rest of the urological community in western Iran. A the patients underwent evaluation with transrectal ultrasound uniform diagnostic, therapeutic and follow-up protocol was used for all (TRUS) and/or endorectal coil magnetic resonance imaging (MRI). patients as follows. History was obtained and physical examination To exclude the possibility of tuberculosis and transitional cell including digital rectal examination was done in all. Kidneys, bladder, carcinoma of the prostatic urethra, it has been recommended to seminal vesicles and prostate were evaluated by transabdominal perform a genital and rectal examination and to request prostate ultrasonography, to rule out genitourinary , tuberculosis, specific antigen (PSA) testing and urinary cytology. Despite hydatidosis, , benign prostate hyperplasia, transitional prostate cancer and obstruction of ejaculatory duct by stones, strictures, polyps, generally being a spontaneously resolving, benign condition, tumors and . By transabdominal sonography, we meant transabdom- hemospermia is being increasingly investigated with expensive 2–5 inal sonography of kidneys, bladder and prostate, not the whole diagnostic technologies such as MRI and TRUS. To our abdominal contents. Testes, too, were evaluated ultrasonographically, to knowledge, based on a review of PubMed, long-term course of rule out , and testis tumors. hemospermia has not been adequately evaluated. Here we report Since 19 July 2008, all sonographies were personally done by the first our experience with 165 hemospermic patients who have been author. Before that time, radiologists performed the sonographies. The visited and followed by the first author during a 15-year period. uniform laboratory evaluation include urinalysis and urine culture, serum PSA, serum markers of testis cancer (alpha feto protein and beta-human chorionic gonadotropin, coagulation parameters, , complete MATERIALS AND METHODS blood count and differential, urine cytology to exclude the possibility of The database for this report includes all patients with hemospermia seen in transitional cell carcinoma of the prostate, and urine smear and culture for our outpatient clinic during the past 16 years. The clinic was launched in tuberculosis. PSA and testis tumor markers were evaluated to rule out 1996. The clinic is a general clinic. We also have been the main prostate and testis cancer, respectively. The sexually transmitted disease

Department of Sexual Medicine, The Rhazes Center for Research in Family Health and Sexual Medicine, and Nosocomial Infections Research Center, Muhammad Zakariya Razi (Rhazes) Boulevard, Kermanshah University of Medical Sciences, Kermanshah, Iran. Correspondence: Dr S Bidhendi, Department of Sexual Medicine, and the Rhazes Center for Research in Family Health and Sexual Medicine, Kermanshah University of Medical Sciences, Muhammad Zakariya Razi (Rhazes) Boulevard, Kermanshah University of Medical Sciences, Kermanshah, Iran. E-mail: [email protected] Received 12 July 2012; revised 4 September 2013; accepted 20 October 2013; published online 5 December 2013 Long-term outcome of hemospermia J Zargooshi et al 84 that is common in this area is gonorrhea. Thus, a urethral smear was spermia was absent in the second visit and never recurred in 149 ordered routinely. Other sexually transmitted diseases were not a concern patients. In the remaining eight, hemospermia was present in at in our cases because we knew the patients’ full medical and sexual history least two visits or its presence was reported to us in the follow-up that was not suggestive of sexually transmitted disease. Thus, we did not calls. In two of these patients, hemospermia occurred only very assess them for other sexually transmitted diseases including chlamydia. If occasionally and responded to the empiric therapy. However, in the laboratory and ultrasonographic evaluations were negative, empiric treatment was given (a fluoroquinolone plus nonsteroidal anti-inflamma- remaining six, hemospermia was persistent, frequently recurring or tory drug). The patients were prescribed a follow-up schedule as follows. high-volume hemospermia. In these six patients, definite etiologies They were asked to present for visit if hemospermia persisted or recurred. were found for hemospermia. One patient had urinary tuberculosis, If completely asymptomatic, they were interviewed regularly (every 6 one had bladder tumor and three had biopsy-proven benign months) by phone, asking about their interim condition. We personally papillary lesions at verumontanum. One patient was diagnosed with called the patients by phone, asking about their interim condition. We bilateral partial ejaculatory duct obstruction by stones. Figure 1 asked: ‘did you have any episode of bloody semen in the intervening time, summarizes the long-term follow-up data. All pathologies were namely after the last visit/call?’ found in young patients (none older than 32 years). If the patients were asymptomatic for 2 consecutive years, then we There was no difference in outcome among patients with more called them yearly. Patients who could not be contacted were deemed lost to follow-up, not cured or failed. than one symptom besides hemospermia, including ejaculatory Considering our clinical and laboratory evaluation of the patients, we are pain or infertility. certain, to a reasonable extent, about other health conditions of the patients. Table 2. Laboratory and sonographic results

RESULTS Parameter Mean Standard deviation Median Mean follow-up was 83 months (range 2–171, median 79, s.d. 48). AFP (ng ml–1) 2.41 1.32 2.2 Mean age was 38 years (range 18–76 years, median 36, s.d. 13.3). B-HCG (U l–1) 1.16 0.61 1.3 Age categories by decade, and associated findings including PSA (ng ml–1) 0.9 0.7 0.7 comorbidities and habits are presented in the Table 1. Of patients, Prostate size (ml) 27.7 11.83 24 106 (64.2%) were 40 years or younger. Regarding the number of Abbreviations: AFP, alpha feto protein; B-HCG, beta-human chorionic times having hemospermia, 18 presented with hemospermia in gonadotropin; PSA, prostate specific antigen. two visits, 2 in three visits and 1 in four visits. The remaining 144 had hemospermia in one visit. Mean prostate volume was 27.7 ml. Mean PSA was 0.9 ng ml–1. PSA was normal in all cases (Table 2). Digital rectal examina- tion and ultrasonography did not find any case of prostate cancer. Coagulation and serum markers of testis cancer were normal in all. Of 165 patients, 8 were lost to follow-up. After empiric treatment of the remaining 157 patients with a fluoroquinolone (Ciprofloxacin) plus an nonsteroidal anti-inflammatory drug (Celecoxib), hemo-

Table 1. Comorbidity/habits

Variable/ Category/condition Number Percent comorbidity

Age 20–29 Years 56 33.9 30–39 Years 48 29.09 40–49 Years 31 18.78 50–59 Years 13 7.87 60–69 Years 12 7.27 70–79 Years 5 3.03

Comorbidity/habits Urinary calculi 41 24.8 Flank pain 21 12.7 Testis pain 18 10.9 Ejaculatory pain 4 2.4 ED 37 22.4 Premature ejaculation 50 30.3 Hypodesire sexual disorder 9 5.4 Lower urinary tract symptoms 35 21.2 Infertility 15 9.09 Epididymo-orchitis 8 4.8 27 16.3 3 1.8 Opium use 14 8.4 Cigarette smoking 14 8.4 Alcohol drinking 8 4.8 Figure 1. The long-term follow-up data of 165 patients with hemospermia.

International Journal of Impotence Research (2014), 83 – 86 & 2013 Macmillan Publishers Limited Long-term outcome of hemospermia J Zargooshi et al 85 Patient compliance with our follow-up schedule was excellent. evaluation is not without risks. At least one patient has been In fact, some of the strengths of our study were long-term follow- reported who died as a direct result of diagnostic evaluation of up and remarkably high follow-up rate with only eight patients hemospermia.1 being lost to follow-up. The relationship, if any, of hemospermia with prostate cancer is In our 15 years’ experience, no patient later developed life- very weak. As was referenced above, most patients with threatening disease. hemospermia will not develop prostate cancer. Nevertheless, in one study,2 hemospermia was found in 0.5% of a prostate cancer screening population, and hemospermia was a significant DISCUSSION predictor of prostate cancer diagnosis after adjusting for age, Most cases of hemospermia result from benign conditions. PSA and digital rectal examination results. However, this study was However, importance of hemospermia for patients is far more criticized on several methodological grounds.3 than its medical importance from the physician’s viewpoint. Although not a common cause of hemospermia, testis cancer Typically, patients present to their primary-care physician after a is a serious, rare cause of hemospermia.4,5 Hemospermia is single episode of hemospermia out of concern for malignancy especially expected when testis cancer involves rete testis. We or venereal disease.6 It has been said that most cases of performed testicular sonography both for this reason, and for hemospermia are the result of iatrogenic, inflammatory and medicolegal reasons, too, because failure to diagnose testicular infectious pathologies.7 It has also been reported that in patients cancer in patients with hemospermia may lead to malpractice younger than 40 years, an infectious cause in the urogenital claims. tract is the most common etiological factor.7 However, our Our own findings suggest that non-recurring, non-persistent, findings do not support an infectious etiology in these patients. low-volume hemospermia need no diagnostic evaluation. Labora- Also it has been stated that in men 40 years and older, iatrogenic tory evaluation was significantly positive in only one patient in hemospermia from urogenital instrumentation or prostate biopsy whom tuberculosis was detected. Ultrasonography and laboratory is the most common cause of blood in the semen.8 None of evaluation did not result in many instances of specific treatment. our patients had such a history in days or weeks preceding Obviously when diagnostic evaluation makes no difference, its use hemospermia. is wastage of time and resources. Up to now, we have evaluated Other etiologies to consider in those 40 years and older include our patients with the above-mentioned diagnostic protocol. genitourinary infections, inflammations, vascular malformations, However, the present assessment of the diagnostic yield of our stones, tumors and systemic disorders that increase bleeding risk.8 protocol clearly shows that it was not necessary, cost effective and A literature review of the etiological studies of hemospermia in helpful. Thus, in the future cases, we reserve our diagnostic 2007 identified a total of 33 tumors (25 prostatic) in 931 cases protocol for high-risk patients only. (3.5%).7 Up to now, we have treated our patients with the above- The dilemma now is how far to investigate these patients, as in mentioned empiric therapeutic regimen. However, the current the majority it is a benign and self-limiting symptom.7 Our study analysis of our results suggests that hemospermia is a self-limiting shows that investigation is unnecessary in the absolute majority. condition and thus does not need medical treatment. Thus, in the We investigated the patients; however, the investigations made future, we may compare the above-mentioned therapeutic no difference. Transabdominal sonography is less sensitive than regimen with watchful waiting. TRUS to detect prostate and seminal vesicle pathologies. However, Elderly patients had no higher incidence of serious underlying TRUS is much more uncomfortable and expensive for the etiologies for hemospermia. Our study shows, to our knowledge patients. In our country, transabdominal sonography of bladder, for the first time, that advanced age makes no difference in prostate and seminal vesicles costs $14.6 while TRUS costs $34.6. hemospermia. MRI of prostate costs $174. In our clinical experience, in Only 3 patients among 165 needed specific therapy: the patient nonhematospermic patients, too, only a scant minority of our with tuberculosis (anti-tuberculosis therapy), the patient with patients agree to be evaluated by TRUS, when given the options bladder tumor (transurethral resection of bladder tumor), and the of transabdominal ultrasound and TRUS. In our long-term patient with bilateral stones at the ejaculatory ducts (unroofing). follow-up, transabdominal sonography withstood the test of All of these patients presented with long, frequently recurring or time. Long-term follow-up showed that no clinically significant high-volume hemospermia, thus making them highly expected pathology was missed by transabdominal sonography. cases for a gainful evaluation. It has been stated that the three factors that dictate the extent of No therapy was given to the three patients with biopsy-proven the evaluation and treatment are patient’s age, the duration and benign papillary lesions of verumontanum. recurrence of the hemospermia, and the presence of any associated hematuria.9 Noninvasive imaging may have an important role in the diagnostic workup of men with hemospermia.10 CONCLUSIONS In our experience, recurrence of hemospermia was very rare, Contribution of our report to the practical knowledge on both immediately and at long-term follow-up. hemospermia includes the following. Diagnostic evaluation of Studies from India,1 Taiwan,2 Korea,3 Italy4 and Japan5 have hemospermia is not worthwhile in the absolute majority of cases. shown the generally benign nature of hemospermia. Advanced age makes no difference in this regard. Only those with What is clear from the above studies is the low impact of the persistent, high-volume or frequently recurring hemospermia findings of MRI and TRUS on treatment of hemospermia, and need to be diagnostically evaluated. The remainder of cases may prominent absence of prostate cancer among the findings. Most be safely and effectively treated with a course of fluoroquinolones of the findings in TRUS and MRI of hemospermic patients are plus non steroidal anti-inflammatory drugs. Recurrence rate of trivial, needing no specific treatment and having no impact on the hemospermia is very low. Incidence of serious disease, too, is patient care, thus, in our view, putting under question the mere negligible. Almost all patients do well in long term. Much more indication of inflicting the patients the costs of unnecessary comfortable, cheap transabdominal ultrasonography is enough for diagnostic expenses. Of course, it is probable that if we were evaluation of hemospermia, with no need of TRUS or MRI. using TRUS more abnormalities would be detected. However, in long-term follow-up, none of our patients developed a serious condition that could be diagnosed if we were using TRUS or MRI, CONFLICT OF INTEREST instead of transabdominal sonography. In addition, diagnostic The authors declare no conflict of interest.

& 2013 Macmillan Publishers Limited International Journal of Impotence Research (2014), 83 – 86 Long-term outcome of hemospermia J Zargooshi et al 86 ACKNOWLEDGMENTS 4 Maheshkumar P, Otite U, Gordon S, Berney DM, Nargund VH. Testicular tumor This work was done to commemorate the shining memory and the 58th birthday of presenting as hematospermia. J Urol 2001; 165:188. Hayaat Zargooshi (1 Ordibehesht 1334–2 Sharivar 1357; 22 April 1955–2 August 5 Vilandt J, Sønksen J, Mikines K, Torp-Pedersen S, Colstrup H. Seminoma in the 1978). Mozhgaan, Newshaa, Aatoosaa and Arya provided assistance. testes associated with haemospermia. BJU Int 2002; 89: 633. 6 Leoca´dio DE, Stein BS. Hemospermia: etiological and management considera- tions. Int Urol Nephrol 2009; 41: 77–83. REFERENCES 7 Ahmad I, Krishna NS. Hemospermia. J Urol 2007; 177: 1653–1658. 1 Hasegawa T, Shimomura T, Yamada H, Ito H, Kato N, Hasegawa N et al. [Fatal 8 Stefanovic KB, Gregg PC, Soung M. Evaluation and treatment of hemospermia. septic shock caused by transrectal needle biopsy of the prostate; a case report]. Am Fam Physician 2009; 80: 1421–1427. [Article in Japanese]. Kansenshogaku Zasshi 2002; 76: 893–897. 9 Polito M, Giannubilo W, d’Anzeo G, Muzzonigro G. Hemospermia: diagnosis and 2 Han M, Brannigan RE, Antenor JA, Roehl KA, Catalona WJ. Association of treatment. Arch Ital Urol Androl 2006; 78: 82–85. hemospermia with prostate cancer. J Urol 2004; 172: 2189–2192. 10 Torigian DA, Ramchandani P. Hemospermia: imaging findings. Abdom Imaging 3 Mahmud SM. Re: association of hemospermia with prostate cancer. JUrol2005; 174: 789. 2007; 32: 29–49.

International Journal of Impotence Research (2014), 83 – 86 & 2013 Macmillan Publishers Limited