{"paper_id":"24aedbfc-2b73-4f98-a1b0-1b882ad4b51f","body_text":"Hematospermia or hemospermia is traditionally defined as the presence of fresh or\naltered blood in semen. It has been reported by physicians for many centuries from\nHippocrates, Galen, Pare, Morgagni, Velpeau, Fournier to Guyon. 1  Historically, majority\nof cases, as many as 70%, were diagnosed as functional and essential or\nidiopathic hematospermia. Functional causes included excessive sexual indulgence or\nintense sexual experiences, prolonged sexual abstinence, and interrupted coitus.\nAlso, sudden emptying of a distended seminal vesicle causes hemorrhage “ex\nvacuo” was thought to be underlying cause of idiopathic\nhematospermia. 2  Currently, with the use of advanced diagnostic tools, the exact\ncause of hematospermia can be found in most cases. There are several factors that\nmight cause hematospermia, including infectious, inflammatory, iatrogenic,\ntraumatic, structural, neoplastic, vascular, and systemic factors ( Table 1 ). 3\nHematospermia is thought to originate from the prostate gland, ejaculatory duct,\nseminal vesicle, vas deferens, epididymis, testis, urethra, or urinary bladder as\nthe causative lesions in different studies. 4  Currently, iatrogenic trauma is the\nmost common cause of hematospermia. Because prostate biopsies have been performed\nmore frequently in older ages, prostate biopsy has become the single most common\ncause of hematospermia in the modern urological era. 5 , 6  However, urogenital infections are still the most common\ncause of hematospermia in men younger than 40 years of age. 7  Inflammatory processes\ncausing mucosal irritation, hyperemia, and edema of the accessory sexual glands and\ntheir ducts may lead to bleeding and the clinical manifestation of hematospermia.\nThis inflammation can be a result of traumatic, chemical, or infectious\ncauses. 8 \nDuctal obstruction and cyst formation of accessory sexual gland and systemic factors\nare other causes of hematospermia. The responsible mechanism in cases with\nobstruction and cyst is thought to be associated with dilatation and distention,\nresulting in rupture of mucosal blood vessels. 9  The most common cause of systemic\nfactor that is associated with hematospermia is an acquired anticoagulable state\nsecondary to drugs. 10 \nHematospermia is rarely associated with any urological malignancies, and it can be\nthe sole symptom in men with urogenital cancer. 11  It has been postulated that fragile\naberrant vessels produced by tumor angiogenic stimuli might contribute to the\nsituation. 12\nThe exact incidence of hematospermia remains unknown and because of its self-limiting\nnature, most men do not observe their ejaculate, and in cases of men who notice it,\nsome patients are hesitant to apply for medical care for this symptom. 13  It is thought to be a\nrelatively rare condition, and it is a symptom accounting for about 1% of\nurological referrals, and only a busy urologist may see more than one case per\nmonth. 2 , 14  In the majority,\nhematospermia is a benign and self-limiting symptom. However, it is a condition that\ncan be a source of great anxiety among patients and their partners who are often\nfearful of cancer or venereal disease. Most patients typically visit their\nprimary-care physician after a single episode of hematospermia, being concerned\nabout this serious condition. 15\nThe main aim of evaluation is to identify significant or treatable underlying causes\nof hematospermia and to re-assure the patient if no causative factor is detected\nafter a full evaluation. 16  The evaluation of hematospermia requires a detailed history,\nphysical examination, and appropriate laboratory investigations and diagnostic\nimaging.\n\nDetailed history is essential for evaluation of hematospermia. The features of the\nhematospermia, including color, amount, timing (coitus and/or masturbation),\nfrequency, and duration, should be ascertained. It is also important to ask about\nrelevant concomitant symptoms ( Table\n2 ). 17 “Hematospermia may be accompanied by other symptoms, but if\nhematospermia is the only symptom, it is defined as monosymptomatic hematospermia.\nHematospermia, when recurrent, is defined as recurrent hematospermia. Also, if it\ncontinues despite the conservative or definitive treatment, it is defined as\npersistent hematospermia.” 10  It is important to obtain a detailed medical history,\nincluding systemic diseases, surgical history, and the use of drugs. The patient is\nquestioned to whether there was any external trauma in the urogenital region. Travel\nhistory to places with schistosomiasis or tuberculosis endemic areas should also be\ninvestigated. 8\n\nSimilar to history, complete physical examination, including systemic, genital, and\nrectal examination, is principal for evaluation of hematospermia. The\npatient’s body temperature and blood pressure should be recorded, and the\nabdomen should be carefully examined to exclude enlargement of liver or spleen or\nthe presence of pelvic masses. The groin, perineum, and external genitalia\nexamination should be examined for any skin lesions, presence of hypospadias, and\nnodularity or induration on testis and spermatic cord. Digital rectal examination is\nperformed to eliminate the possibility of prostate and seminal vesicle infective\ndisorders, cysts, and pathological masses. After digital rectal examination,\nurethral meatus should be re-examined for presence of bloody discharge. 18 , 19\n\nLaboratory tests for evaluation of hematospermia include urine analysis and bacterial\nculture, urethral swab, Meares-Stamey four-glass test, semen analysis and culture,\nblood cell count, serum biochemical and coagulation parameters, and serum\nprostate-specific antigen levels. These tests should be tailored to individual\npatients. 12 , 18\nUrine analysis and culture-antibiogram are recommended for all patients with\nhematospermia, as these tests are low-cost and help confirm the presence of\ninfection and hematuria in patients. 20 , 21  However, traditionally the rate of positive culture results\nis low but current laboratory techniques can identify more microorganisms. The\npresence of hematuria is a risk factor for more serious underlying pathology.\nTherefore, if it occurs, a complete evaluation for hematuria should be\nperformed. 21\nIf a sterile pyuria is detected then further investigations are required to exclude\nchronic inflammatory disorder, such as chronic non-bacterial prostatitis,\ntuberculosis, schistosomiasis, and viral infections. Urethral swabs/cultures,\nMeares-Stamey four-glass test, semen cultures, and viral serology are tests that are\nused for this purpose. 16  Urethral swab/cultures for  N. gonorrhoeae  and\n C. trachomatis  should also be performed when sexually\ntransmitted diseases are suspected or urethritis is accompanied with\nhematospermia. 3 , 16  Semen\nanalysis is helpful to distinguish between hematospermia and pseudo-hematospermia.\nIt should also be performed when hematospermia is associated with low ejaculate\nvolume and/or infertility. 22\nHematospermia is related to an increased risk of prostate cancer. Because of this,\nserum prostate-specific antigen level measurement is obligatory in patients older\nthan 40 years of age and/or when hematospermia is recurrent. 11  Coagulation studies\nare recommended for patients with hematological disease, patients using any\nanticoagulant/antifibrinolytic drugs, and patients with recurrent hematospermia,\nespecially >2 months, due to this situation are associated with coagulation\ndisorders. 14 \nIn addition, complete blood count, creatinine and electrolytes, uric acid, and liver\nfunction tests should be performed if history and/or examination suggests chronic\ndisorders. 12\n\nVaso-vesiculography is almost never used today in the diagnostic evaluation of\nhematospermia. This invasive technique provides little data to detect the\netiology of hematospermia. Also, it requires x-ray and may cause serious side\neffects, such as vasal injury and stricture. 1 , 23\nComputerized tomography has limited value in the etiologic determination of\nhematospermia owing to its x-ray necessity, lack of soft-tissue contrast, and\nlimitations in the evaluation of smallcaliber structures, such as the\nejaculatory duct or vas deferens and in the evaluation of the internal structure\nof the seminal vesicle and prostate gland. 1 , 24\nMaheshkumar et al 25  reported persistent hematospermia as presenting symptom of\ntesticular cancer in a patient who did not have any associated symptoms and\nphysical examination findings. Thus, scrotal ultrasonography should be performed\nin patients with persistent hematospermia, or in case of any associated symptom,\nin order to rule out testicular pathology as an underlying cause of\nhematospermia. 10 , 25\nMany authors have reported that transrectal ultrasonography TRUS is a safe,\nsimple, easily accessible, cost-effective, radiation free, and relatively\nnoninvasive imaging modality that can clearly image seminal vesicles,\nejaculatory ducts, and the prostate objectively. 4  Its accurate diagnostic rate in\npatients with recurrent or persistent hematospermia is up to\n95%. 26 , 27 \nHowever, TRUS has some limitations, such as images obtained with ultrasonography\nare subject to observer variation, spatial resolution, and soft-tissue contrast\nmay not permit complete evaluation of the ejaculatory duct and seminal vesicle,\nand therefore might not show the origin of bleeding, and as a result of this, it\nhas a false positive/negative rate of approximately 50%. Thus, it has\nbeen suggested that TRUS should not be considered definitive but as primary\nscreening modality for patients with recurrent or persistent\nhaematospermia. 27 , 28 \nTRUS can provide definitive diagnosis if a lesion is detected or confirmed by\nmeans of TRUS-guided seminal vesicle aspiration, prostate and seminal vesicle\nbiopsy, and semino-vesiculography. It can also be used as a guide for treatment\nof hematospermia, such as TRUS-guided cyst aspiration, TRUS-guided laser\nincision of cyst, TRUSguided balloon dilation of ejaculatory duct in an\nantegrade fashion, and transurethral resection of ejaculatory duct (TURED) with\nTRUS-guided chromotubation. 24 , 29\nMagnetic resonance imaging, owing to its excellent soft-tissue contrast,\nmultiplanar capabilities, independence from the operator, and lack of ionization\nradiation, plays an important role as a noninvasive imaging modality in the\ndiagnostic workup of recurrent or persistent hematospermia. 30  Although costly,\ncurrent gold standard for imaging of structural and inflammatory/infective\nchanges in accessory sex gland and their ducts is MRI. In the presence of\nsuspected cancer, it should include dynamic contrast imaging that provides\nadditional information regarding tissue perfusion. In addition, MRI angiography\nprovides further information for localizing bleeding. 24 , 30  Magnetic\nresonance imaging has at least 80% diagnostic performance in patients\nwith recurrent or persistent hematospermia. Endorectal phased-array coil is\nsuperior to external phased-array coil for evaluation of the prostatic region,\nbut it causes discomfort to the patient. However, Sosna et al 31  showed the image\nquality at the external coil at 3.0 T to be comparable with the endorectal coil\nat 1.5 T.\nIn a large series of patients with recurrent or persistent hematospermia, Li et\nal 28 \nreported that there is no significant difference in the positive rate of\nabnormal imaging between MRI and TRUS (86.3% vs. 84.3%,\n P  >.05), while MRI provides more precise causative\ninformation, particularly regarding ejaculatory duct obstruction and hemorrhage\nlocation, than TRUS. According to American College of Radiology, MRI is\nindicated when TRUS results are negative or inconclusive ( Tables 3  and  4 ). 24\nIn the literature, pelvic angiography has been rarely reported to be useful for\ndiagnosis of patients with persistent massive hematospermia and hematuria due to\nvascular masses, such as prostatic hemangioma, arteriovenous malformation, and\nvarices. If an arterial source of hemorrhage is identified, transcatheter\narterial embolization or electrofulguration can be performed during the same\nsession as well. 32\nWhen hematospermia is accompanied by hematuria in elderly patients or all\nattempts to diagnose the disease fails, in high risk patients with recurrent or\npersistent hematospermia, rigid or flexible urethrocystoscopy should be\nconsidered. It allows direct vision of urethra, prostate, bladder neck, and\nbladder and their pathologic conditions. Concurrent massage of the prostate and\nseminal vesicles may be useful for localizing bleeding. Due to its very poor\ndiagnostic performance, urethrocystoscopy is not recommended routinely for\ndiagnostic workup of hematospermia, as well as renal tract ultrasound and\nintravenous urography. 33\nTransurethral seminal vesiculoscopy (TSV) is another endoscopic technique that\ncan directly visualize etiological lesions in the ejaculatory duct and seminal\nvesicles with high sensitivity and specificity. A definite diagnosis rate of\n93.1% was reported in the first large-scale report of patients with\nrecurrent or persistent hematospermia. 34  In a prospective study, Xing et\nal 26 \ncompared TSV and TRUS for the diagnosis of persistent hematospermia. They\nreported that overall diagnostic yield of TSV was significantly superior to that\nof TRUS (74.5% vs. 45.3%,  P  < .001) and\nthe diagnostic yield of combining TSV and TRUS was significantly higher than\nthat of each modality alone (both  P  < .001). In\naddition, TSV is not only a diagnostic but also a treatment tool for ejaculatory\nduct and seminal vesicle pathologies. However, even though it is a minimally\ninvasive procedure that requires anesthesia, TSV is currently not standardized,\nfailures still occur, long-term safety is uncertain, and can lead to\ncomplications, such as epididymitis, ejaculation abnormality, and injury of the\nseminal vesicle and rectum. 23 , 34\nFirst step of treatment should be allaying the anxiety of the patients and their\npartners via giving sufficient information about hematospermia. Due to natural\nhistory of hematospermia, reassurance and follow-up without any treatment will\nbe adequate for many patients. In a prospective study investigating natural\nhistory of hematospermia in patients who underwent watchful waiting without any\nempirical treatment, Furuya et al 9  reported that the persistence rates\nof hematospermia were 57.7% at 1 month, 34.2% at 3 months,\n23.3% at 6 months, 12.5% at 1 year, and 7.6% at 2 years.\nIatrogenic causes of hematospermia usually resolve spontaneously within\napproximately 10 ejaculations or on an average 11 days, but it can continue for\nup to 2 months. 5 , 6\nProper treatment of hematospermia that include specific and empiric treatments\ndepends on the underlying pathology. If urogenital infection is affirmed, the\ntreatment of appropriate antibiotic, antiparasitic, or antiviral agents is\nindicated on the basis of the sensitivity of the cultured organism. 20  Also, systemic\nconditions, if any, should be treated appropriately.\nIf infection is suspected, but no pathological findings are determined, empiric\ntreatment is suitable. Antibiotics should be capable of penetrating the\nprostate-blood barrier (e.g., fluoroquinolones, tetracyclines, macrolides,\ntrimethoprim-sulfamethoxazole, and metronidazole) and non-steroidal\nanti-inflammatory drugs (e.g., ibuprofen and celocoxib). In a large, but\nnon-controlled and retrospective study, Zargooshi et al. 15  reported that in\n94.9% of patients, hematospermia did not recur after empirical treatment\n(ciprofloxacin plus celocoxib). Other empiric treatments contain\nantifibrinolytic, antiandrogenic, and estrogenic agents, such as aminocaproic\nacid, 35 \nfinasteride, 36  and ethinyl estradiol. 37  These agents should only be used\nin selected patients with persistent hematospermia, as there is insufficient\nevidence on the use of such agents.\nSpecific surgical treatment is given, if it is required, when vascular anomalies,\npolyps, calcification, cysts, or other pathological conditions are detected.\nUrethroscope-guided electroexcision and/or fulguration of polyps and vascular\nanormalies in posterior urethra, 29  direct drug injection to seminal\nvesicles guided by TRUS, 38  TRUS-guided cyst aspiration with or without\nsclerotherapy, 39  TRUS-guided transurethral laser incision of\ncyst, 40 \ntransurethral unroofing or laparoscopic management of seminal vesicle\ncysts, 41 \nTURED with or without TRUS-guided choromotubation, 42  TRUS and fluoroscopic assisted\ntransurethral incision of ejaculatory ducts, 43  urethroscopy and TRUS or\nCT/MRI-guided recanalization and dilatation of ejaculatory duct, 22 , 44  TSV-guided\nincision of obstructed ejaculatory duct, coagulate hemorrhagic mucosa, and\nfragment stones in the ejaculatory duct or seminal vesicle by using electric or\nlaser energy systems 7 , 45 \nare methods that can be performed for this purpose.\nIn conclusion, to address how the novel algorithm in the management of\nhematospermia should be, the first step is to rule out pseudo-hematospermia,\nwhich could be because of bleeding from sexual partner source, hematuria,\nurethral bleeding, and melanospermia. 19  If in doubt, a “condom\ntest” should be performed, where the semen is collected and then checked\nfor blood. 20  Once\ntrue hematospermia has been affirmed, the diagnostic process should be initiated\nwith a clinical history and physical examination. Afterward, 3 key factors help\nguide further evaluation ( Figure\n1 ): age, duration of hematospermia, and presence of concomitant\nsymptoms or risk factors since recurrent or persistent hemospermia may indicate\na more serious underlying pathology, especially in patients over 40 years of\nage. 17 \nHowever, the evidence basis for the investigation and management of\nhaematospermia remains lacking. 13 , 33","source_license":"CC-BY-4.0","license_restricted":false}