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 tuberculosis, 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; semen
INTRODUCTION Hemospermia (hematospermia) is the presence of blood in the semen. Despite being a source of considerable anxiety in patients, hemospermia and its long-term clinical course has not been adequately addressed in the sexual medicine literature. Reported experience in various countries shows that hemospermia is rarely associated with any significant urologic pathology. In India,1 among 35 patients with hemospermia, infection was the most common cause (40%). In Taiwan,2 no prostate cancer was found in 40 patients with hemospermia. In Korea,3 again, no prostate cancer found in 17 patients with hemospermia. In Italy,4 no malignant disease was demonstrated in 90 patients with hemospermia. In Japan,5 too, no malignant lesions were found in the prostate or seminal vesicles of 46 patients with hemospermia. In these studies, the patients underwent evaluation with transrectal ultrasound (TRUS) and/or endorectal coil magnetic resonance imaging (MRI). To exclude the possibility of tuberculosis and transitional cell carcinoma of the prostatic urethra, it has been recommended to perform a genital and rectal examination and to request prostate specific antigen (PSA) testing and urinary cytology. Despite generally being a spontaneously resolving, benign condition, hemospermia is being increasingly investigated with expensive diagnostic technologies2–5 such as MRI and TRUS. To our knowledge, based on a review of PubMed, long-term course of hemospermia has not been adequately evaluated. Here we report our experience with 165 hemospermic patients who have been visited and followed by the first author during a 15-year period. MATERIALS AND METHODS The database for this report includes all patients with hemospermia seen in our outpatient clinic during the past 16 years. The clinic was launched in 1996. The clinic is a general urology clinic. We also have been the main
provider of specialized sexual medicine health care and the sole destination for the referral cases of sexual medicine in the Kermanshah province and the neighboring five provinces of western Iran (Ilam, Loristan, Kurdistan, Khuzestan and Hamadan). From the first day of launching the clinic, we have recorded the patients’ full clinical and laboratory data into our electronic information storage and retrieval system, the UNESCO’s database management system CDS/ISIS. For the purpose of this article, a search of the chief complaint field of our electronic data set was done for the keyword hemospermia. After saving the search results, electronic files of the identified patients were reviewed and relevant information was extracted and summarized. Based on our database search, from 2 January 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 period, we have seen 36 252 patients with urologic complaints. Thus, considering our very large case load, our hemospermia cases are representative of the rest of the urological community in western Iran. A uniform diagnostic, therapeutic and follow-up protocol was used for all patients as follows. History was obtained and physical examination including digital rectal examination was done in all. Kidneys, bladder, seminal vesicles and prostate were evaluated by transabdominal ultrasonography, to rule out genitourinary schistosomiasis, tuberculosis, hydatidosis, prostatitis, benign prostate hyperplasia, transitional prostate cancer and obstruction of ejaculatory duct by stones, strictures, polyps, tumors and cysts. By transabdominal sonography, we meant transabdominal sonography of kidneys, bladder and prostate, not the whole abdominal contents. Testes, too, were evaluated ultrasonographically, to rule out epididymitis, orchitis and testis tumors. Since 19 July 2008, all sonographies were personally done by the first author. Before that time, radiologists performed the sonographies. The 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, semen analysis, complete blood count and differential, urine cytology to exclude the possibility of transitional cell carcinoma of the prostate, and urine smear and culture for tuberculosis. PSA and testis tumor markers were evaluated to rule out 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 ordered routinely. Other sexually transmitted diseases were not a concern in our cases because we knew the patients’ full medical and sexual history that was not suggestive of sexually transmitted disease. Thus, we did not assess them for other sexually transmitted diseases including chlamydia. If laboratory and ultrasonographic evaluations were negative, empiric treatment was given (a fluoroquinolone plus nonsteroidal anti-inflammatory drug). The patients were prescribed a follow-up schedule as follows. They were asked to present for visit if hemospermia persisted or recurred. If completely asymptomatic, they were interviewed regularly (every 6 months) by phone, asking about their interim condition. We personally called the patients by phone, asking about their interim condition. We asked: ‘did you have any episode of bloody semen in the intervening time, namely after the last visit/call?’ If the patients were asymptomatic for 2 consecutive years, then we called them yearly. Patients who could not be contacted were deemed lost to follow-up, not cured or failed. Considering our clinical and laboratory evaluation of the patients, we are certain, to a reasonable extent, about other health conditions of the patients.
RESULTS Mean follow-up was 83 months (range 2–171, median 79, s.d. 48). Mean age was 38 years (range 18–76 years, median 36, s.d. 13.3). Age categories by decade, and associated findings including comorbidities and habits are presented in the Table 1. Of patients, 106 (64.2%) were 40 years or younger. Regarding the number of times having hemospermia, 18 presented with hemospermia in 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 examination 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.
spermia was absent in the second visit and never recurred in 149 patients. In the remaining eight, hemospermia was present in at least two visits or its presence was reported to us in the follow-up calls. In two of these patients, hemospermia occurred only very occasionally and responded to the empiric therapy. However, in the remaining six, hemospermia was persistent, frequently recurring or high-volume hemospermia. In these six patients, definite etiologies were found for hemospermia. One patient had urinary tuberculosis, one had bladder tumor and three had biopsy-proven benign papillary lesions at verumontanum. One patient was diagnosed with bilateral partial ejaculatory duct obstruction by stones. Figure 1 summarizes the long-term follow-up data. All pathologies were found in young patients (none older than 32 years). There was no difference in outcome among patients with more than one symptom besides hemospermia, including ejaculatory pain or infertility. Table 2.
Laboratory and sonographic results
Parameter –1
AFP (ng ml ) B-HCG (U l–1) PSA (ng ml–1) Prostate size (ml)
Mean
Standard deviation
Median
2.41 1.16 0.9 27.7
1.32 0.61 0.7 11.83
2.2 1.3 0.7 24
Abbreviations: AFP, alpha feto protein; B-HCG, beta-human chorionic gonadotropin; PSA, prostate specific antigen.
Comorbidity/habits
Variable/ comorbidity
Category/condition
Number
Percent
56 48 31 13 12 5
33.9 29.09 18.78 7.87 7.27 3.03
41 21 18 4 37 50 9 35 15 8 27 3 14 14 8
24.8 12.7 10.9 2.4 22.4 30.3 5.4 21.2 9.09 4.8 16.3 1.8 8.4 8.4 4.8
Age 20–29 30–39 40–49 50–59 60–69 70–79
Years Years Years Years Years Years
Comorbidity/habits Urinary calculi Flank pain Testis pain Ejaculatory pain ED Premature ejaculation Hypodesire sexual disorder Lower urinary tract symptoms Infertility Epididymo-orchitis Varicocele Spermatocele Opium use Cigarette smoking Alcohol drinking
International Journal of Impotence Research (2014), 83 – 86
Figure 1. The long-term follow-up data of 165 patients with hemospermia. & 2013 Macmillan Publishers Limited
Long-term outcome of hemospermia J Zargooshi et al
85 Patient compliance with our follow-up schedule was excellent. In fact, some of the strengths of our study were long-term followup and remarkably high follow-up rate with only eight patients being lost to follow-up. In our 15 years’ experience, no patient later developed lifethreatening disease. DISCUSSION Most cases of hemospermia result from benign conditions. However, importance of hemospermia for patients is far more than its medical importance from the physician’s viewpoint. Typically, patients present to their primary-care physician after a single episode of hemospermia out of concern for malignancy or venereal disease.6 It has been said that most cases of hemospermia are the result of iatrogenic, inflammatory and infectious pathologies.7 It has also been reported that in patients younger than 40 years, an infectious cause in the urogenital tract is the most common etiological factor.7 However, our findings do not support an infectious etiology in these patients. Also it has been stated that in men 40 years and older, iatrogenic hemospermia from urogenital instrumentation or prostate biopsy is the most common cause of blood in the semen.8 None of our patients had such a history in days or weeks preceding hemospermia. Other etiologies to consider in those 40 years and older include genitourinary infections, inflammations, vascular malformations, stones, tumors and systemic disorders that increase bleeding risk.8 A literature review of the etiological studies of hemospermia in 2007 identified a total of 33 tumors (25 prostatic) in 931 cases (3.5%).7 The dilemma now is how far to investigate these patients, as in the majority it is a benign and self-limiting symptom.7 Our study shows that investigation is unnecessary in the absolute majority. We investigated the patients; however, the investigations made no difference. Transabdominal sonography is less sensitive than TRUS to detect prostate and seminal vesicle pathologies. However, TRUS is much more uncomfortable and expensive for the patients. In our country, transabdominal sonography of bladder, prostate and seminal vesicles costs $14.6 while TRUS costs $34.6. MRI of prostate costs $174. In our clinical experience, in nonhematospermic patients, too, only a scant minority of our patients agree to be evaluated by TRUS, when given the options of transabdominal ultrasound and TRUS. In our long-term follow-up, transabdominal sonography withstood the test of time. Long-term follow-up showed that no clinically significant pathology was missed by transabdominal sonography. It has been stated that the three factors that dictate the extent of the evaluation and treatment are patient’s age, the duration and 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 In our experience, recurrence of hemospermia was very rare, both immediately and at long-term follow-up. Studies from India,1 Taiwan,2 Korea,3 Italy4 and Japan5 have shown the generally benign nature of hemospermia. What is clear from the above studies is the low impact of the findings of MRI and TRUS on treatment of hemospermia, and prominent absence of prostate cancer among the findings. Most of the findings in TRUS and MRI of hemospermic patients are trivial, needing no specific treatment and having no impact on the patient care, thus, in our view, putting under question the mere indication of inflicting the patients the costs of unnecessary diagnostic expenses. Of course, it is probable that if we were 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, instead of transabdominal sonography. In addition, diagnostic & 2013 Macmillan Publishers Limited
evaluation is not without risks. At least one patient has been reported who died as a direct result of diagnostic evaluation of hemospermia.1 The relationship, if any, of hemospermia with prostate cancer is very weak. As was referenced above, most patients with 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 predictor of prostate cancer diagnosis after adjusting for age, PSA and digital rectal examination results. However, this study was criticized on several methodological grounds.3 Although not a common cause of hemospermia, testis cancer is a serious, rare cause of hemospermia.4,5 Hemospermia is especially expected when testis cancer involves rete testis. We performed testicular sonography both for this reason, and for medicolegal reasons, too, because failure to diagnose testicular cancer in patients with hemospermia may lead to malpractice claims. Our own findings suggest that non-recurring, non-persistent, low-volume hemospermia need no diagnostic evaluation. Laboratory evaluation was significantly positive in only one patient in whom tuberculosis was detected. Ultrasonography and laboratory evaluation did not result in many instances of specific treatment. Obviously when diagnostic evaluation makes no difference, its use is wastage of time and resources. Up to now, we have evaluated our patients with the above-mentioned diagnostic protocol. However, the present assessment of the diagnostic yield of our protocol clearly shows that it was not necessary, cost effective and helpful. Thus, in the future cases, we reserve our diagnostic protocol for high-risk patients only. Up to now, we have treated our patients with the abovementioned empiric therapeutic regimen. However, the current analysis of our results suggests that hemospermia is a self-limiting condition and thus does not need medical treatment. Thus, in the future, we may compare the above-mentioned therapeutic regimen with watchful waiting. Elderly patients had no higher incidence of serious underlying etiologies for hemospermia. Our study shows, to our knowledge for the first time, that advanced age makes no difference in hemospermia. Only 3 patients among 165 needed specific therapy: the patient with tuberculosis (anti-tuberculosis therapy), the patient with bladder tumor (transurethral resection of bladder tumor), and the patient with bilateral stones at the ejaculatory ducts (unroofing). All of these patients presented with long, frequently recurring or high-volume hemospermia, thus making them highly expected cases for a gainful evaluation. No therapy was given to the three patients with biopsy-proven benign papillary lesions of verumontanum. CONCLUSIONS Contribution of our report to the practical knowledge on hemospermia includes the following. Diagnostic evaluation of hemospermia is not worthwhile in the absolute majority of cases. Advanced age makes no difference in this regard. Only those with persistent, high-volume or frequently recurring hemospermia need to be diagnostically evaluated. The remainder of cases may be safely and effectively treated with a course of fluoroquinolones plus non steroidal anti-inflammatory drugs. Recurrence rate of hemospermia is very low. Incidence of serious disease, too, is negligible. Almost all patients do well in long term. Much more comfortable, cheap transabdominal ultrasonography is enough for evaluation of hemospermia, with no need of TRUS or MRI. CONFLICT OF INTEREST The authors declare no conflict of interest.
International Journal of Impotence Research (2014), 83 – 86
Long-term outcome of hemospermia J Zargooshi et al
86 ACKNOWLEDGMENTS This work was done to commemorate the shining memory and the 58th birthday of Hayaat Zargooshi (1 Ordibehesht 1334–2 Sharivar 1357; 22 April 1955–2 August 1978). Mozhgaan, Newshaa, Aatoosaa and Arya provided assistance.
REFERENCES 1 Hasegawa T, Shimomura T, Yamada H, Ito H, Kato N, Hasegawa N et al. [Fatal septic shock caused by transrectal needle biopsy of the prostate; a case report]. [Article in Japanese]. Kansenshogaku Zasshi 2002; 76: 893–897. 2 Han M, Brannigan RE, Antenor JA, Roehl KA, Catalona WJ. Association of hemospermia with prostate cancer. J Urol 2004; 172: 2189–2192. 3 Mahmud SM. Re: association of hemospermia with prostate cancer. J Urol 2005; 174: 789.
International Journal of Impotence Research (2014), 83 – 86
4 Maheshkumar P, Otite U, Gordon S, Berney DM, Nargund VH. Testicular tumor presenting as hematospermia. J Urol 2001; 165: 188. 5 Vilandt J, Sønksen J, Mikines K, Torp-Pedersen S, Colstrup H. Seminoma in the testes associated with haemospermia. BJU Int 2002; 89: 633. 6 Leoca´dio DE, Stein BS. Hemospermia: etiological and management considerations. Int Urol Nephrol 2009; 41: 77–83. 7 Ahmad I, Krishna NS. Hemospermia. J Urol 2007; 177: 1653–1658. 8 Stefanovic KB, Gregg PC, Soung M. Evaluation and treatment of hemospermia. Am Fam Physician 2009; 80: 1421–1427. 9 Polito M, Giannubilo W, d’Anzeo G, Muzzonigro G. Hemospermia: diagnosis and treatment. Arch Ital Urol Androl 2006; 78: 82–85. 10 Torigian DA, Ramchandani P. Hemospermia: imaging findings. Abdom Imaging 2007; 32: 29–49.
& 2013 Macmillan Publishers Limited
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 tuberculosis, 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; semen
INTRODUCTION Hemospermia (hematospermia) is the presence of blood in the semen. Despite being a source of considerable anxiety in patients, hemospermia and its long-term clinical course has not been adequately addressed in the sexual medicine literature. Reported experience in various countries shows that hemospermia is rarely associated with any significant urologic pathology. In India,1 among 35 patients with hemospermia, infection was the most common cause (40%). In Taiwan,2 no prostate cancer was found in 40 patients with hemospermia. In Korea,3 again, no prostate cancer found in 17 patients with hemospermia. In Italy,4 no malignant disease was demonstrated in 90 patients with hemospermia. In Japan,5 too, no malignant lesions were found in the prostate or seminal vesicles of 46 patients with hemospermia. In these studies, the patients underwent evaluation with transrectal ultrasound (TRUS) and/or endorectal coil magnetic resonance imaging (MRI). To exclude the possibility of tuberculosis and transitional cell carcinoma of the prostatic urethra, it has been recommended to perform a genital and rectal examination and to request prostate specific antigen (PSA) testing and urinary cytology. Despite generally being a spontaneously resolving, benign condition, hemospermia is being increasingly investigated with expensive diagnostic technologies2–5 such as MRI and TRUS. To our knowledge, based on a review of PubMed, long-term course of hemospermia has not been adequately evaluated. Here we report our experience with 165 hemospermic patients who have been visited and followed by the first author during a 15-year period. MATERIALS AND METHODS The database for this report includes all patients with hemospermia seen in our outpatient clinic during the past 16 years. The clinic was launched in 1996. The clinic is a general urology clinic. We also have been the main
provider of specialized sexual medicine health care and the sole destination for the referral cases of sexual medicine in the Kermanshah province and the neighboring five provinces of western Iran (Ilam, Loristan, Kurdistan, Khuzestan and Hamadan). From the first day of launching the clinic, we have recorded the patients’ full clinical and laboratory data into our electronic information storage and retrieval system, the UNESCO’s database management system CDS/ISIS. For the purpose of this article, a search of the chief complaint field of our electronic data set was done for the keyword hemospermia. After saving the search results, electronic files of the identified patients were reviewed and relevant information was extracted and summarized. Based on our database search, from 2 January 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 period, we have seen 36 252 patients with urologic complaints. Thus, considering our very large case load, our hemospermia cases are representative of the rest of the urological community in western Iran. A uniform diagnostic, therapeutic and follow-up protocol was used for all patients as follows. History was obtained and physical examination including digital rectal examination was done in all. Kidneys, bladder, seminal vesicles and prostate were evaluated by transabdominal ultrasonography, to rule out genitourinary schistosomiasis, tuberculosis, hydatidosis, prostatitis, benign prostate hyperplasia, transitional prostate cancer and obstruction of ejaculatory duct by stones, strictures, polyps, tumors and cysts. By transabdominal sonography, we meant transabdominal sonography of kidneys, bladder and prostate, not the whole abdominal contents. Testes, too, were evaluated ultrasonographically, to rule out epididymitis, orchitis and testis tumors. Since 19 July 2008, all sonographies were personally done by the first author. Before that time, radiologists performed the sonographies. The 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, semen analysis, complete blood count and differential, urine cytology to exclude the possibility of transitional cell carcinoma of the prostate, and urine smear and culture for tuberculosis. PSA and testis tumor markers were evaluated to rule out 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 ordered routinely. Other sexually transmitted diseases were not a concern in our cases because we knew the patients’ full medical and sexual history that was not suggestive of sexually transmitted disease. Thus, we did not assess them for other sexually transmitted diseases including chlamydia. If laboratory and ultrasonographic evaluations were negative, empiric treatment was given (a fluoroquinolone plus nonsteroidal anti-inflammatory drug). The patients were prescribed a follow-up schedule as follows. They were asked to present for visit if hemospermia persisted or recurred. If completely asymptomatic, they were interviewed regularly (every 6 months) by phone, asking about their interim condition. We personally called the patients by phone, asking about their interim condition. We asked: ‘did you have any episode of bloody semen in the intervening time, namely after the last visit/call?’ If the patients were asymptomatic for 2 consecutive years, then we called them yearly. Patients who could not be contacted were deemed lost to follow-up, not cured or failed. Considering our clinical and laboratory evaluation of the patients, we are certain, to a reasonable extent, about other health conditions of the patients.
RESULTS Mean follow-up was 83 months (range 2–171, median 79, s.d. 48). Mean age was 38 years (range 18–76 years, median 36, s.d. 13.3). Age categories by decade, and associated findings including comorbidities and habits are presented in the Table 1. Of patients, 106 (64.2%) were 40 years or younger. Regarding the number of times having hemospermia, 18 presented with hemospermia in 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 examination 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.
spermia was absent in the second visit and never recurred in 149 patients. In the remaining eight, hemospermia was present in at least two visits or its presence was reported to us in the follow-up calls. In two of these patients, hemospermia occurred only very occasionally and responded to the empiric therapy. However, in the remaining six, hemospermia was persistent, frequently recurring or high-volume hemospermia. In these six patients, definite etiologies were found for hemospermia. One patient had urinary tuberculosis, one had bladder tumor and three had biopsy-proven benign papillary lesions at verumontanum. One patient was diagnosed with bilateral partial ejaculatory duct obstruction by stones. Figure 1 summarizes the long-term follow-up data. All pathologies were found in young patients (none older than 32 years). There was no difference in outcome among patients with more than one symptom besides hemospermia, including ejaculatory pain or infertility. Table 2.
Laboratory and sonographic results
Parameter –1
AFP (ng ml ) B-HCG (U l–1) PSA (ng ml–1) Prostate size (ml)
Mean
Standard deviation
Median
2.41 1.16 0.9 27.7
1.32 0.61 0.7 11.83
2.2 1.3 0.7 24
Abbreviations: AFP, alpha feto protein; B-HCG, beta-human chorionic gonadotropin; PSA, prostate specific antigen.
Comorbidity/habits
Variable/ comorbidity
Category/condition
Number
Percent
56 48 31 13 12 5
33.9 29.09 18.78 7.87 7.27 3.03
41 21 18 4 37 50 9 35 15 8 27 3 14 14 8
24.8 12.7 10.9 2.4 22.4 30.3 5.4 21.2 9.09 4.8 16.3 1.8 8.4 8.4 4.8
Age 20–29 30–39 40–49 50–59 60–69 70–79
Years Years Years Years Years Years
Comorbidity/habits Urinary calculi Flank pain Testis pain Ejaculatory pain ED Premature ejaculation Hypodesire sexual disorder Lower urinary tract symptoms Infertility Epididymo-orchitis Varicocele Spermatocele Opium use Cigarette smoking Alcohol drinking
International Journal of Impotence Research (2014), 83 – 86
Figure 1. The long-term follow-up data of 165 patients with hemospermia. & 2013 Macmillan Publishers Limited
Long-term outcome of hemospermia J Zargooshi et al
85 Patient compliance with our follow-up schedule was excellent. In fact, some of the strengths of our study were long-term followup and remarkably high follow-up rate with only eight patients being lost to follow-up. In our 15 years’ experience, no patient later developed lifethreatening disease. DISCUSSION Most cases of hemospermia result from benign conditions. However, importance of hemospermia for patients is far more than its medical importance from the physician’s viewpoint. Typically, patients present to their primary-care physician after a single episode of hemospermia out of concern for malignancy or venereal disease.6 It has been said that most cases of hemospermia are the result of iatrogenic, inflammatory and infectious pathologies.7 It has also been reported that in patients younger than 40 years, an infectious cause in the urogenital tract is the most common etiological factor.7 However, our findings do not support an infectious etiology in these patients. Also it has been stated that in men 40 years and older, iatrogenic hemospermia from urogenital instrumentation or prostate biopsy is the most common cause of blood in the semen.8 None of our patients had such a history in days or weeks preceding hemospermia. Other etiologies to consider in those 40 years and older include genitourinary infections, inflammations, vascular malformations, stones, tumors and systemic disorders that increase bleeding risk.8 A literature review of the etiological studies of hemospermia in 2007 identified a total of 33 tumors (25 prostatic) in 931 cases (3.5%).7 The dilemma now is how far to investigate these patients, as in the majority it is a benign and self-limiting symptom.7 Our study shows that investigation is unnecessary in the absolute majority. We investigated the patients; however, the investigations made no difference. Transabdominal sonography is less sensitive than TRUS to detect prostate and seminal vesicle pathologies. However, TRUS is much more uncomfortable and expensive for the patients. In our country, transabdominal sonography of bladder, prostate and seminal vesicles costs $14.6 while TRUS costs $34.6. MRI of prostate costs $174. In our clinical experience, in nonhematospermic patients, too, only a scant minority of our patients agree to be evaluated by TRUS, when given the options of transabdominal ultrasound and TRUS. In our long-term follow-up, transabdominal sonography withstood the test of time. Long-term follow-up showed that no clinically significant pathology was missed by transabdominal sonography. It has been stated that the three factors that dictate the extent of the evaluation and treatment are patient’s age, the duration and 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 In our experience, recurrence of hemospermia was very rare, both immediately and at long-term follow-up. Studies from India,1 Taiwan,2 Korea,3 Italy4 and Japan5 have shown the generally benign nature of hemospermia. What is clear from the above studies is the low impact of the findings of MRI and TRUS on treatment of hemospermia, and prominent absence of prostate cancer among the findings. Most of the findings in TRUS and MRI of hemospermic patients are trivial, needing no specific treatment and having no impact on the patient care, thus, in our view, putting under question the mere indication of inflicting the patients the costs of unnecessary diagnostic expenses. Of course, it is probable that if we were 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, instead of transabdominal sonography. In addition, diagnostic & 2013 Macmillan Publishers Limited
evaluation is not without risks. At least one patient has been reported who died as a direct result of diagnostic evaluation of hemospermia.1 The relationship, if any, of hemospermia with prostate cancer is very weak. As was referenced above, most patients with 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 predictor of prostate cancer diagnosis after adjusting for age, PSA and digital rectal examination results. However, this study was criticized on several methodological grounds.3 Although not a common cause of hemospermia, testis cancer is a serious, rare cause of hemospermia.4,5 Hemospermia is especially expected when testis cancer involves rete testis. We performed testicular sonography both for this reason, and for medicolegal reasons, too, because failure to diagnose testicular cancer in patients with hemospermia may lead to malpractice claims. Our own findings suggest that non-recurring, non-persistent, low-volume hemospermia need no diagnostic evaluation. Laboratory evaluation was significantly positive in only one patient in whom tuberculosis was detected. Ultrasonography and laboratory evaluation did not result in many instances of specific treatment. Obviously when diagnostic evaluation makes no difference, its use is wastage of time and resources. Up to now, we have evaluated our patients with the above-mentioned diagnostic protocol. However, the present assessment of the diagnostic yield of our protocol clearly shows that it was not necessary, cost effective and helpful. Thus, in the future cases, we reserve our diagnostic protocol for high-risk patients only. Up to now, we have treated our patients with the abovementioned empiric therapeutic regimen. However, the current analysis of our results suggests that hemospermia is a self-limiting condition and thus does not need medical treatment. Thus, in the future, we may compare the above-mentioned therapeutic regimen with watchful waiting. Elderly patients had no higher incidence of serious underlying etiologies for hemospermia. Our study shows, to our knowledge for the first time, that advanced age makes no difference in hemospermia. Only 3 patients among 165 needed specific therapy: the patient with tuberculosis (anti-tuberculosis therapy), the patient with bladder tumor (transurethral resection of bladder tumor), and the patient with bilateral stones at the ejaculatory ducts (unroofing). All of these patients presented with long, frequently recurring or high-volume hemospermia, thus making them highly expected cases for a gainful evaluation. No therapy was given to the three patients with biopsy-proven benign papillary lesions of verumontanum. CONCLUSIONS Contribution of our report to the practical knowledge on hemospermia includes the following. Diagnostic evaluation of hemospermia is not worthwhile in the absolute majority of cases. Advanced age makes no difference in this regard. Only those with persistent, high-volume or frequently recurring hemospermia need to be diagnostically evaluated. The remainder of cases may be safely and effectively treated with a course of fluoroquinolones plus non steroidal anti-inflammatory drugs. Recurrence rate of hemospermia is very low. Incidence of serious disease, too, is negligible. Almost all patients do well in long term. Much more comfortable, cheap transabdominal ultrasonography is enough for evaluation of hemospermia, with no need of TRUS or MRI. CONFLICT OF INTEREST The authors declare no conflict of interest.
International Journal of Impotence Research (2014), 83 – 86
Long-term outcome of hemospermia J Zargooshi et al
86 ACKNOWLEDGMENTS This work was done to commemorate the shining memory and the 58th birthday of Hayaat Zargooshi (1 Ordibehesht 1334–2 Sharivar 1357; 22 April 1955–2 August 1978). Mozhgaan, Newshaa, Aatoosaa and Arya provided assistance.
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International Journal of Impotence Research (2014), 83 – 86
4 Maheshkumar P, Otite U, Gordon S, Berney DM, Nargund VH. Testicular tumor presenting as hematospermia. J Urol 2001; 165: 188. 5 Vilandt J, Sønksen J, Mikines K, Torp-Pedersen S, Colstrup H. Seminoma in the testes associated with haemospermia. BJU Int 2002; 89: 633. 6 Leoca´dio DE, Stein BS. Hemospermia: etiological and management considerations. Int Urol Nephrol 2009; 41: 77–83. 7 Ahmad I, Krishna NS. Hemospermia. J Urol 2007; 177: 1653–1658. 8 Stefanovic KB, Gregg PC, Soung M. Evaluation and treatment of hemospermia. Am Fam Physician 2009; 80: 1421–1427. 9 Polito M, Giannubilo W, d’Anzeo G, Muzzonigro G. Hemospermia: diagnosis and treatment. Arch Ital Urol Androl 2006; 78: 82–85. 10 Torigian DA, Ramchandani P. Hemospermia: imaging findings. Abdom Imaging 2007; 32: 29–49.
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