Hematospermia is defined as blood in the semen. While often perceived as having little significance, blood in the ejaculate can cause great concern to the men who experience it. The condition is common, with many episodes going unnoticed; therefore, the prevalence of hematospermia remains unknown.
Hematospermia is most commonly secondary to an infectious or inflammatory etiology and follows a benign and self-limited course.[1] As such, no further diagnostic workup is generally needed, especially in younger men; however, in some patients, hematospermia may be the first indicator of other urologic diseases or systemic disorders (see DDx/Diagnostic Considerations).
The advent of newer imaging modalities, especially transrectal ultrasonography, has altered both the diagnosis and the treatment of hematospermia. In 2009, Aslam et al developed an algorithm to guide the management of these patients.[2]
For patient education information, see the Men's Health Center and Cancer Center, as well as Male Reproductive Organs and Functions, BPH (Prostate, Benign Prostatic Hyperplasia), Prostate Infections, and Prostate Cancer.
Hematospermia has been written about for centuries. Hippocrates, Galen, Pare, Morgagni, and Fournier all commented on this condition. The first American report appeared in 1894, and excellent contemporary reviews have been published.[3, 4, 5, 6]
For an understanding of the causes of hematospermia, a working knowledge of the relevant anatomy of the ejaculatory complex is useful.
The seminal vesicles are androgen-dependent accessory organs that produce and store seminal fluid, which is essential to male fertility. The seminal vesicles are best studied ultrasonographically. Normal seminal vesicles are flat paired structures that lie cephalad to the prostate behind the bladder and have a bow-tie appearance on transverse imaging. They are symmetric, well-defined, saccular, elongated organs.
In its normal collapsed state, the center of the seminal vesicle is homogeneous, with areas of increased echogenicity corresponding to the folds of secretory epithelium. In the distended state, the wall is visibly composed of 2 distinct layers.
The dimensions of the seminal vesicles vary with age, but not with the ejaculatory state. Upon transrectal ultrasonography (TRUS), the dimensions are estimated to be 30 ± 5 mm in length, 15 ± 4 mm in width, and 13.7 ± 3.7 mL in mean volume. The age of the patient and degree of prostate enlargement have been shown to cause variation in the size of the seminal vesicles.
The vasa deferentia act as conduits, carrying sperm between the epididymis and the ejaculatory ducts via the vasal ampullae. The vasal ampullae pass medially to the seminal vesicles and are best seen using transaxial TRUS views.
The seminal vesicles and vasal ampullae join together to form the ejaculatory duct. The ejaculatory duct travels through the prostate and enters the urethra at the level of the verumontanum. The junction between the seminal vesicle and the ejaculatory duct lies within the prostate and is difficult to see in a healthy unobstructed system. Small echodensities are frequently seen at the junction of the ejaculatory ducts and the verumontanum in the urethra. These areas provide useful landmarks and are thought to represent concretions within the periurethral glands surrounding the verumontanum.
Hematospermia is usually associated with inflammatory conditions of the seminal vesicles or prostate. The condition is often self-limited and resolves within 1-2 months. If hematospermia persists beyond 2 months, further workup is recommended to determine the cause. In approximately half the cases, the etiology is declared idiopathic. However, this may reflect an incomplete evaluation.
Pathophysiology of the prostate can be a cause of hematospermia. The most common etiology is prostate biopsy, which produces self-limited hematospermia that resolves within approximately 1 month.
Other authors have recognized prostate cancer as an etiologic factor. A study by Han et al reported a significantly increased risk of prostate cancer among men with hematospermia. Of 139 men with hematospermia, 19 (13.7%) were diagnosed with prostate cancer. In the overall cohort of 26,126 patients, the prostate cancer detection rate was 6.5%. On logistic regression analysis, the presence of hematospermia was a significant predictor of prostate cancer diagnosis.[7] However, sampling bias concerns have been raised by investigators as this study was conducted among men undergoing screening for prostate cancer. It is unclear whether the findings can be apply to a general population of men with hematospermia.[8]
This remains a controversial area of investigation. Prando reported on a series of 86 men with hematospermia, who were subsequently evaluated with endorectal MRI and found prostate cancer in only one patient.[9] A study of 161,258 men with urologic complaints reported a 3.2% rate of prostate cancer among 342 patients with hematospermia.[10]
In a review by Ng et al of 300 cases of hematospermia, 13 prostate cancers were detected (5.7%), all in men over 40 years of age with either with a prostate-specific antigen (PSA) level higher than 3.0 ng/dL or an abnormal digital rectal examination (DRE). Those researchers recommended screening for prostate cancer in men over 40 who present with hematospermia.[11]
In a study by Hakam et al of 56,157 men of hematospermia, only 47 were found to have a urologic cancer: 28 with prostate cancer (0.05%), nine with testicular cancer (0.016%), six with prostate carcinoma in situ (0.01%), and four with bladder cancer (0.007%). These authors used data from a United States insurance claims database to identify men who were diagnosed with hematospermia in the absence of hematuria, elevated prostate-specific antigen, or a past history of urologic cancer.[12]
Hematospermia can also be caused by prostatic telangiectasia and varices. This diagnosis is confirmed with endoscopic evaluation using either flexible or rigid cystoscopy.
Prostatitis is often thought to cause hematospermia, although no specific association has been reported. If the patient has signs and symptoms of acute bacterial prostatitis, specific treatment is indicated. If symptoms of chronic pelvic pain syndrome (CPPS) are present, urine culture and then culture of expressed prostatic secretions should be performed. Hematospermia is not a recognized symptom of CPPS.
In a study of 52 patients with hematospermia, Etherington et al found a significant number of patients with prostatic calculi.[13]
Another publication reported on cystic dilation of the prostatic utricle in association with hematospermia. Furuya and Kato reported on 30 of 138 men with hematospermia who had a midline cyst of the prostate. Nineteen men underwent transperineal biopsy; hemorrhagic fluid was confirmed in 13 of the men. Four of the men were cured with transurethral unroofing.[14]
With the advent of TRUS-guided prostate biopsy for the diagnosis of prostate cancer, a new etiology of hematospermia has emerged. Many centers have reviewed their experience with this complication.[15]
The rate of hematospermia following transrectal biopsy of the prostate has varied from 9-84%. In one study, 25% of patients who underwent TRUS biopsy had concomitant hematospermia and hematuria after the procedure. Berger et al reported on 5957 biopsies performed in 4303 men. This group found that hematospermia occurred after approximately 36% of the biopsies. They concluded that, in this situation, the hematospermia is generally self-limited and requires no specific therapy.[16]
Some authors have recommended administering finasteride beginning 2 weeks prior to TRUS biopsy of the prostate to reduce the risk of postprocedure hematuria. While no studies have specifically examined the impact of finasteride on the occurrence of hematospermia, this condition may be improved with the use of this medication.
Transurethral resection of the prostate is also associated with subsequent hematospermia. A study by Shen et al described 80 consecutive men who underwent transurethral prostate resection and found that hematospermia developed in 2.5% of the men.{ref14
Brachytherapy as treatment for prostate cancer involves inserting radioactive seeds directly into the prostate. This procedure has been shown to cause hematospermia in up to 17% of patients who undergo this treatment.[17]
Urethritis has long been recognized as a cause of hematospermia, especially in younger men.
Other urethral lesions leading to hematospermia include cysts, polyps, condylomata, and strictures. Benign urethral polyps can occur following failure of the invagination process of the prostatic glandular epithelium.[18] In one case series, 20% of patients with urethral polyps had hematospermia as their presenting symptom. In another study, causes of hematospermia included urethritis (7% of cases), condylomata (1.5%), and stricture disease (1.5%).
Many authors have cited congenital and acquired seminal vesicle cysts as a cause of hematospermia. Congenital cysts result from an error in embryological development and are associated with ipsilateral renal agenesis and/or ipsilateral congenital absence of the vas deferens.
Acquired seminal vesicle cysts generally result from infectious processes, and malignancies of the seminal vesicles are a rare cause of hematospermia. In one review of 37 patients with primary carcinoma of the seminal vesicle, only 6 patients (16%) had hematospermia.
More recently, amyloidosis of the seminal vesicles has been described to be related to hematospermia.[19] Fifty-six men with hematospermia were evaluated with MRI, and obvious intravesicular hemorrhage was associated with hyperintense signal of the seminal vesicles on MRI. After resolution of the bleeding, the signal returned to a hypointense state on MRI. Twelve of these patients underwent transperineal biopsy; four were found to have seminal vesicle amyloidosis. In all cases, hematospermia resolved with conservative intervention.
The most recent data suggest that seminal vesicle and ejaculatory duct cysts or hemorrhagic lesions account for most identifiable causes of hemospermia. In one study, 52 of 86 men were found to have lesions in association with hemospermia. Of these men, 51 had some type of seminal vesicle, ejaculatory duct, or prostatic benign or hemorrhagic lesion. Only one case of prostate cancer was identified.[9]
Infections and inflammatory disorders account for 40% of cases. Infectious causes of hematospermia include, but are not limited to, tuberculosis (TB), HIV infection, and cytomegalovirus infection.[20] Yu and colleagues found that 11% of a cohort of 65 patients with genitourinary TB had hematospermia during their disease.[21]
A review of 16 men with hematospermia who presented to a sexually transmitted infection clinic found pathogens in 12 of the men. These included urine, genitourinary, or serum cultures or titers positive for herpes simplex virus in five, Chlamydia trachomatis in four, Enterococcus faecalis in two, and Ureaplasma urealyticum in one. Culture-specific antibiotics were administered, and hematospermia resolved in all the patients.[22]
Genitourinary schistosomiasis has been reported as a cause of hematospermia.[23, 24] Although these patients often have extensive bladder involvement, Schistosoma hematobium ova are only occasionally found in the ejaculate.
Hydatid disease, a parasitic infection caused by the Echinococcus worm, has also been associated with hematospermia.[25]
Trauma has been cited as a cause of hematospermia in several case reports. Such case reports include hematospermia occurring following hemorrhoidal sclerosing injection, urethral self-instrumentation, and testicular and perineal blunt trauma. Hematospermia following transrectal prostate needle biopsy should also be included in this category.
A systematic review and meta-analysis by Radfar et al found that the rate of microscopic and macroscopic hematospermia was significantly higher after extracorporeal shock wave lithotripsy (ESWL) for the treatment of urolithiasis. Hematospermia resolved by 3 months.[26]
Systemic disorders that are associated with hematospermia include hypertension, chronic liver disease, amyloidosis, lymphoma, and bleeding diatheses (eg, von Willebrand disease[27, 28] ). In one case-controlled study of patients undergoing therapy for hypertension, the prevalence of hematospermia was no higher than in the general population; however, hematospermia resolved in several patients when their hypertension was controlled.[29]
Risk factors for hematospermia in patients who are hypertensive include the following:
Kurkar and colleagues identified hyperuricemia as a possible cause of hematospermia. Compared with their patients who had idiopathic hematospermia, those with hyperuricemia (median serum uric acid level, 9.3 mg/dL) were significantly younger (median of 31.5 vs 45 years) and more likely to complain of painful ejaculation (68.2% vs 9.5%).Hematospermia resolved completely in all patients of the hyperuricemia group in 1-4 months, compared with only 25% of the idiopathic group.[30]
United States
The true prevalence of hematospermia is unknown. It is likely that many cases escape the patient's notice, and remain unrecognized and unreported. Review of a United States insurance claims database from 2010 to 2018 found that the annual average incidence rate of hematospermia was 56.6 per 100,000 in 2010 and increased to 73.6 per 100,000 in 2018.[12]
Data collected after TRUS-guided biopsy of the prostate suggest that up to 36.3% of men undergoing removal of 6-15 cores develop postprocedure hematospermia. Increasing the number of cores did not significantly increase the frequency of hematospermia.[16] Other studies have found rates of hematospermia following TRUS-guided biopsy to be as high as 84%.[31]
Hematospermia can occur in males of any age. In younger men (< 40 y), hematospermia is uniformly benign. A review of a large, nationally representative US database found only one diagnosis of cancer (testicular) in 15,106 patients under 40 years of age—a malignancy rate of 0.01%.[12] Even in older men, hematospermia is rarely associated with malignancy.
Hematospermia is usually self-limited; however, when hematospermia is an indicator of underlying urologic disease, the prognosis depends on the underlying disease.
A Japanese study of 198 patients with hematospermia found that a high urinary pH (7.0-9.0) or any abnormal finding on imaging studies of the prostate were independent predictors of longer duration of hematospermia. Patients with both of those factors were especially likely to have prolonged hematospermia; they constituted a significantly higher proportion of the group whose hematospermia persisted for more than 6 months, compared with the the group with a duration of less than 2 months.[32]
When hematospermia is visible macroscopically, the color of the ejaculate may vary depending on how much time has passed since hemorrhage took place. If fresh blood is present, the semen may range in color from light red to brownish; with old bleeding, the semen may be dark brown or contain black clots.[33]
In addition to confirming that the blood is not in the patient’s urine or from his sexual partner, questions about the following can often help to narrow the differential diagnoses associated with hematospermia:
Most patients have more than one episode, occurring over weeks to months. While no uniformly accepted definition of chronic hematospermia has been determined, blood in the ejaculate that persists for more than 10 ejaculations requires further evaluation. While some authorities use duration (ie, months) as a guideline, the discrepancy in the frequency of ejaculations among men renders this approach less reliable.
Patient age is important. In patients younger than 40 years, urogenital infections are the most common cause of hematospermia, and a simple, focused workup is often sufficient. In men older than 40 years with persistent hematospermia or associated symptoms such as hematuria, excluding urogenital malignancy is essential.[5]
The physical examination should include measuring the patient's blood pressure, because severe hypertension is associated with hematospermia.[35] This association is well recognized; however, the exact mechanism by which it occurs is unclear. The basis may be similar to that of the association between hypertension and epistaxis (nosebleeds).
Careful attention should be paid to the following during physical examination; the penis and urethral meatus should be carefully inspected to rule out any lesions that may bleed and contribute to the ejaculate.
The vasa should be palpated and followed along their course to ensure their presence and to rule out any induration or nodularity. Any nodularity in the absence of prior vasal surgery (including vasectomy) should raise concern for a tuberculous infection of the vasa. Alternatively, nodules within the vas rarely represent extension of prostatic or bladder malignancies.
Upon digital rectal examination (DRE), special attention should be given to the seminal vesicles and the presence of any midline masses. The seminal vesicles are routinely nonpalpable structures. If they are palpable, this generally indicates significant underlying pathology. In older men (> 50 y), specific attention should also be given to the prostate because hematospermia may rarely be a harbinger of prostate cancer.
In younger men with nonpersistent hematospermia, only a digital rectal examination (DRE), along with a check of vital signs, is required as part of a careful physical examination. In older men (>50 y) with nonpersistent hematospermia without concomitant hematuria upon urinalysis, a basic evaluation consists of a DRE and a prostate-specific antigen measurement. Persistent hematospermia (>2 months without defined etiology) warrants further workup, as described below.
Urinalysis and culture may prove helpful because urogenital infections may be associated with hematospermia; because this test is of low cost and a positive result suggests an etiology, urine culture is recommended in all patients who present with hematospermia.
In younger men, urethritis should be considered in the differential diagnoses. Testing should be performed to help exclude nonspecific and gonococcal urethritis.
If the history suggests exposure to tuberculosis (TB), urine culture for acid-fast bacilli may prove helpful because TB can be a cause, though rare, of hematospermia.
Blood in the urine mandates a more extensive evaluation of the genitourinary tract. The workup should proceed according to American Urological Association guidelines[36] and can include any of the following, depending on the patient's age, risk factors, and whether the hematuria is asymptomatic or symptomatic as well as microscopic vs gross.
The role of semen analysis and culture remains unclear. While advocated by some authors, the significance of a positive culture result remains uncertain because this may simply represent urethral contamination. Semen analysis may prove helpful in the differentiation of true hematospermia from other causes of ejaculate discoloration.
Smith et al reported two cases of melanospermia as the presenting feature of malignant melanoma.[37] If necessary, the two can be differentiated based on chromatography findings.
Prostate-specific antigen analysis is recommended in all men older than 50 years, African-American men, and men older than 40 years with a family history of prostate cancer. Hematospermia may be a harbinger of prostate cancer.
Coagulation studies are recommended in men of all ages with persistent hematospermia (>2 months) because this condition is associated with coagulopathies.
Otherwise, laboratory analyses should be limited to an evaluation for bleeding disorders if clinically warranted.
The advent of transrectal ultrasonography (TRUS) has provided physicians with an important tool for evaluating patients with hematospermia and has relegated the role of studies such as intravenous urography, vasography, and seminal vesiculography to that of only historical interest.[38] TRUS and MRI allow clear visualization of the seminal vesicles, prostate, and ampullary portions of the vas. As a result, etiologic factors can now be identified more frequently.
TRUS is not recommended for routine use in patients initially presenting with hematospermia.[11] However, TRUS can be valuable for evaluating older patients or those with persistent hemospermia or associated symptoms.[5]
Three large series have evaluated the utility of TRUS in the investigation of patients with chronic hematospermia. In a study of 52 patients, Etherington et al found that 83% of these patients had abnormalities on imaging such as prostatic calculi, or abnormalities of the seminal vesicles (eg, calculi, dilatation, cysts, abnormal lobulation, asymmetry).[13]
Worischeck and Parra evaluated 26 patients with hematospermia using TRUS. They found abnormalities in 92% of patients, which included dilatated seminal vesicles (30%), ejaculatory duct cysts (15%), ejaculatory duct calculi (15%), seminal vesicle calculi (15%), and müllerian duct remnants (7%). No ultrasonographic evidence of malignancy was found.[39]
In a study by Raviv et al of 115 consecutive patients with hematospermia who were evaluated with TRUS, all the patients were found to have an abnormality, almost all of them benign. Abnormalities included hypoechogenicity within the peripheral zone of the prostate, prostatic calculi, cysts within the seminal vesicles, and/or dilation of the seminal vesicles or ejaculatory ducts. In 10 patients a 12-core TRUS-guided biopsy of the prostate was taken; none of the samples were positive for tumor.[40]
Maeda et al used MRI to study men with hematospermia and found abnormalities, including cyst formation or dilatation, in 14 of 15 patients. In 11 of 15 patients there was abnormal signal intensity of the seminal vesicles though to be secondary to subacute hemorrhage. [41]
The best delineation of the seminal vesicles and their surrounding structures has been achieved with T2-weighted imaging.
MRI can help detect changes in anatomic structure secondary to endocrine therapy, radiation, inflammatory disorders, and neoplasia; however, the biggest advantage of MRI over TRUS is its ability to demonstrate hemorrhage within the seminal vesicles or prostate.
A 2008 study by Prando evaluated the utility of endorectal MRI in patients with chronic hematospermia and found it to be highly sensitive in terms of diagnosing abnormalities associated with hematospermia. Most of these abnormalities were benign.[9]
Persistent hematospermia (>3 mo) without an antecedent cause or persistent hematospermia associated with an abnormality on ultrasonography or MRI may prompt further evaluation. Yang et al described a technique in which a 6F or 9F rigid ureteroscope is used to gain access to the prostatic utricle or ejaculatory ducts. In this manner, the scope is used to visually inspect the seminal vesicles, and a biopsy specimen may then be obtained from any abnormal area. In a study of this procedure by Yang et al, seminal vesicle hemorrhage was found in 62% of patients, and calculi were found in 16%.[42] A study by Xing et al, found that transurethral seminal vesiculoscopy was superior to transrectal ultrasonography for detecting calculi and obstruction/stricture in men with persistent hematospermia.[38]
Although CT scans have been used to study the morphology of the seminal vesicles, no studies have been published that specifically target men with hematospermia.
Given the association of hematospermia with urethral and prostatic lesions and in the absence of any urogenital infection or other discernible etiology, cystourethroscopy may aid the clinician in pinpointing the source of the bleeding. Of course, all patients with concomitant hematuria should undergo cystoscopy and an evaluation of the upper urinary tract.
The primary goal in the management of hematospermia is to properly counsel patients who have a condition that can be extremely anxiety-provoking but is often self-limited and benign. Hematospermia is rarely associated with significant pathology, especially in younger men. The three factors that dictate the extent of the evaluation and treatment include the following:
Urogenital infections require appropriate antibiotic therapy, which normally resolves the problem. In all men, enterobacteria (especially Escherichia coli) should be covered if empiric therapy is used. In younger men, concomitant therapy for chlamydial infections should also be used if an infectious etiology is pursued. A fluoroquinolone should adequately treat both organisms. Current guidelines from the Centers for Disease Control and Prevention list levofloxacin (500 mg orally once daily for 7 days) as an alternative regimen for urogenital chlamydial infections, but recommend doxycycline 100 mg orally 2 times/day for 7 days.[43]
If the patient is allergic to fluoroquinolones or cannot afford this class of drugs, a combination of trimethoprim/sulfamethoxazole and doxycycline is often successful. A 2-week course is usually sufficient. Concomitant inflammation may be treated with ibuprofen or other nonsteroidal anti-inflammatory drugs.
Urethral or prostatic varices are best fulgurated. Cysts, of either the seminal vesicles or prostatic urethra, can be aspirated transrectally.
Multiple clinical studies have shown that transurethral endoscopy of the seminal vesicles is a safe and effective treatment for hematospermia. Outcomes are particularly good in patients with seminal tract calculi or cysts.[44] Transutricular seminal vesiculoscopy guided by real-time transrectal ultrasonography has also proved effective in managing persistent hematospermia.[45]
For calculi in the ejaculatory ducts or seminal vesicles, Oh and Seo reported successful resolution of hematospermia in 13 of 15 patients with endoscopic treatment and a holmium laser. After dilation with a guidewire and ureteral serial dilator and introduction of a semi-rigid ureteroscope, a holmium laser was used to incise the obstructed ejaculatory duct, coagulate hemorrhagic mucosa, and fragment the calculi in the ejaculatory duct or seminal vesicles. Stones were removed using a basket and forceps.[46]
Liao et al reported successful treatment of refractory hematospermia and ejaculatory duct obstruction with transurethral endoscopy or seminal vesiculoscopy. The specific endoscopic procedures used varied with the etiology of the obstruction and included fenestration in the prostatic utricle, irrigation, lithotripsy, stone removal, electroexcision, fulguration, and transurethral resection/incision of the ejaculatory duct.[33]
Currently, no evidence suggests that the injection of any substance, coagulant or sclerosant, has any role in the management of hematospermia. Fuse and colleagues injected coagulant substances into dilated seminal vesicles under transrectal ultrasound guidance in seven patients with hematospermia, there was temporary resolution however, the hematospermia returned several months later.[47]
Bleeding diatheses or other systemic disorders should be managed in the appropriate manner.
In men with coexisting bladder outlet obstruction, a 5-alpha reductase inhibitor may be used. A prospective controlled study also showed that treatment with the 5-alpha reductase inhibitor finasteride, 5 mg daily for 3 months, produced subjective relief of idiopathic refractory hematospermia in 8 of 12 patients within 2-5 weeks; remission was confirmed by semen analysis.[48]
No rationale currently exists for the use of oral agents, such as estrogens or corticotropins, which have been used in the past.
Patients in whom bleeding prostatic variceal veins are suggested as the cause of hematospermia are candidates for fulguration. After infectious causes have been excluded in cases of persistent hematospermia, cystourethroscopy is performed. If large friable prostatic veins are discovered and examination findings are otherwise normal, fulguration with a Bugbee or loop electrode can be performed. Prior to fulguration, a biopsy should be performed on any suggestive lesions.
Endoscopy of the ejaculatory ducts and seminal vesicles uses a semirigid ureteroscope to cannulate the ejaculatory duct and allows the surgeon to examine the duct, seminal vesicle, and ampulla of the vas.[38, 49, 50] However, the author reserves this technique for only the most refractory cases of hematospermia that involve significant physiologic comorbidity (eg, urinary retention or persistent hematuria) or psychological trauma (avoidance of ejaculation).
In the absence of recurrence, no specific follow-up for hematospermia is warranted. Chronic (>2 mo) or recurrent hematospermia should be evaluated on the basis of the associated clinical features.