Hematospermia is defined as blood in the semen. While often perceived as a symptom of little significance, blood in the ejaculate can cause great concern to the men who experience it. The condition is common, and many episodes go unnoticed; therefore, the prevalence of hematospermia remains unknown. In most patients with hematospermia, no further diagnostic workup is needed; however, in some patients, hematospermia may be the first indicator of other urologic diseases.
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 Fletcher, Leary, Marshall, and Ganabathi have subsequently published excellent contemporary reviews on the subject. The advent of newer imaging modalities has altered both the diagnosis and the treatment of hematospermia.
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 gland is homogenous, 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. Caudally, the seminal vesicles diverge laterally.
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.
MRI findings may also help delineate the normal anatomy of the seminal vesicles. Using MRI, the signal intensity of the seminal vesicles can be compared with the tissues surrounding them (ie, skeletal muscle, fat, urine). The signal intensity on T1-weighted spin-echo images of normal seminal vesicles in men is similar to or slightly higher than that of skeletal muscles and is always greater than that of urine. On T2-weighted images, the signal intensity varies. In prepubertal boys and men older than 70 years (androgen-deprived males), the signal intensity is generally lower than that of skeletal muscle or urine. Convolutions of the seminal vesicles are best observed on T2-weighted images or on T1-weighted images with the use of intravenous contrast agents.
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.
The true prevalence of hematospermia is unknown because most ejaculations occur intravaginally and hematospermia often remains unrecognized.
Recent data collected after TRUS-guided biopsy of the prostate suggest that up to 36.3% of men undergoing 6-15 cores develop postprocedure hematospermia. Increasing the number of cores did not significantly increase the frequency of hematospermia.
Hematospermia affects only males.
Hematospermia can occur in males of any age. In younger men (< 40 y), hematospermia is uniformly benign. Even in older men, it is rarely associated with malignancy.
A good patient history that concentrates on trauma, infection, and bleeding disorders often helps to narrow the differential diagnoses associated with hematospermia.
Most men with hematospermia are young (mean age, < 40 y) and have symptoms ranging in duration from 1-24 months.
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.
The physical examination should include measuring the patient's blood pressure because severe hypertension is associated with hematospermia. This association is well recognized; however, the exact mechanism by which it occurs is unclear. It may have a similar basis to the association of hypertension with epistaxis (nosebleeds).
The penis should be carefully inspected to rule out any lesions that may bleed and contribute to the ejaculate.
The vasa should be palpated along their entire 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 is occasionally a harbinger of prostate cancer.
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.
Conditions of the prostate
Lesions of the prostate account for many cases of hematospermia. The most common etiology is prostate biopsy, which produces self-limited hematospermia that resolves within approximately 1 month. In one case series, prostatitis was cited as the etiology in 30% of the patients. Other authors have recognized prostate cancer as an etiologic factor. Malignancies account for 2% of cases. In a long-term follow-up study of 150 patients with hematospermia, only 6 patients eventually developed prostate carcinoma, and none had prostate carcinoma diagnosed at the time of the initial evaluation.
However, a recent 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. This is still a controversial area of investigation. More recently, Prando (2008) reported on a series of 86 men with hemospermia and found prostate cancer in only one patient.
Hematospermia can also be caused by prostatic telangiectasia and varices. In rare cases, a patient with hematospermia may be diagnosed with prostatic varices only after cystoscopic examination while experiencing an erection. In order to diagnose this condition, flexible (preferably) or rigid cystoscopy is conducted after pharmacological induction of an erection.
Prostatitis is often thought to cause hematospermia, although no specific association has been reported. Upon signs and symptoms of acute bacterial prostatitis, specific treatment is indicated. If symptoms of chronic pelvic pain prostatitis syndrome are present, urine culture and then culture of expressed prostatic secretions should be performed. Hematospermia is not a recognized symptom of chronic prostatitis syndrome.
In a study of 52 patients with hematospermia, Etherington et al found a significant number of patients with prostatic calculi.
Another (2005) 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.
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.
The rate of hematospermia following transrectal biopsy of the prostate has varied from 9-45%. In one study, 25% of patients who underwent TRUS biopsy had concomitant hematospermia and hematuria after the procedure. In 2004, 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.
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.
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.
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.
Conditions of the urethra
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. In one case series, 20% of patients with urethral polyps had hematospermia as their presenting symptom. In another study, urethritis, condylomata, and stricture disease represented the cause of hematospermia in 7%, 1.5%, and 1.5% of the patients, respectively.
Seminal vesicle lesions
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 39 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. Fifty-six men with hematospermia were evaluated with MRI, and obvious intravesicular hemorrhage was associated with hyperintense signal (brighter) of the seminal vesicles on MRI. After resolution of the bleeding, the signal returned to a hypointense state (lighter) on MRI. Twelve of these patients underwent transperineal biopsy; 4 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. Fifty-two of 86 men in a recent study 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.
Infections and inflammatory disorders account for 40% of cases. Infectious causes of hematospermia include tuberculosis (TB), HIV infection, and cytomegalovirus infection. Yu and colleagues found that 11% of a cohort of 65 patients with genitourinary TB had hematospermia during their disease.
A recent 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 5, Chlamydia trachomatis in 4, Enterococcus faecalis in 2, and Ureaplasma urealyticum in one. Culture-specific antibiotics were administered, and hematospermia resolved in all the patients.
Several authors have reported schistosomiasis as a cause of hematospermia. 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.
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.
Approximately 2% of cases are believed to result from trauma other than that related to recent prostate biopsy.
Systemic disorders that are associated with hematospermia include hypertension, chronic liver disease, amyloidosis, lymphoma, and bleeding diatheses (von Willebrand disease). In one case-controlled study of patients undergoing hypertension therapy, the prevalence of hematospermia was no higher than in the general population; however, hematospermia resolved in several patients when their hypertension was controlled.
Risk factors for hematospermia in patients who are hypertensive include severe uncontrolled hypertension, elevated serum creatinine levels, severe proteinuria, and renovascular disease.
Urinalysis and culture may prove helpful because urogenital infections may be associated with hematospermia. Unfortunately, the rate of positive culture results is low, varying from 6-29%. 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.
If the history suggests exposure to TB, urine culture for acid-fast bacilli may prove helpful because TB is a cause of hematospermia in as many as 13% of patients in some series.
In younger men, urethritis should be considered in the differential diagnoses, and urethral swabs should be obtained and examined to help exclude nonspecific and gonococcal urethritis.
Blood in the urine mandates a more extensive evaluation of the genitourinary tract. At the authors' institution, patients presenting with hematuria undergo the following tests: urinalysis, urine culture, urine cytology, CT scan of the abdomen and pelvis with contrast, and cystoscopy.
Semen analysis and culture
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 2 cases of melanospermia as the presenting feature of malignant melanoma. Melanin produces a dark brown or black discoloration of semen rather than red or pink, which occurs with hematospermia. If necessary, the two can be differentiated based on chromatography findings. Normal semen should appear as a coagulum that liquifies over a 5- to 25-minute period.
Otherwise, laboratory analyses should be limited to an evaluation for bleeding disorders.
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 mo) because this condition is associated with coagulopathies.
The advent of TRUS has provided physicians with the single most important new 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. 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.
Recently, 2 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 a significant number of patients with prostatic calculi and abnormalities of the seminal vesicles, including calculi, dilatation, cysts, abnormal lobulation, and asymmetry.
More recently, 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 in either series.
The incidence of seminal vesicle abnormalities in these two series is similar to that in earlier studies that used biochemical assays and seminal vesiculography. Unfortunately, neither of these studies cited the mean patient age. This factor may have aided clinicians in stratifying patients in different treatment algorithms.
Maeda et al used MRI to study men with hematospermia and found abnormalities, including cyst formation or dilatation, in 14 of 15 patients.
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.
Endorectal MRI was recently found to be highly sensitive in terms of diagnosing abnormalities associated with hemospermia. Most of these abnormalities were benign.
CT scan: 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.
Cystourethroscopy: 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 tract.
Persistent hematospermia (>3 mo) without an antecedent cause or persistent hematospermia associated with an abnormality on ultrasonography or MRI may prompt further evaluation. Recently, a technique has been described whereby 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.
Seminal vesicle hemorrhage was found in 62% of patients, and calculi were found in 16%.
The primary goal in the management of hematospermia is to allay the anxiety of the frightened patient. Hematospermia is rarely associated with significant pathology, especially in younger men. The 3 factors that dictate the extent of the evaluation and treatment include (1) patient age, (2) the duration and recurrence of the hematospermia, and (3) the presence of any associated hematuria. Most malignancies associated with hematospermia occur in patients older than 40 years. Chronic hematospermia warrants more aggressive intervention to identify an etiologic factor.
In younger men with nonpersistent hematospermia, only a 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. All patients with concomitant hematuria need an evaluation of their upper (with intravenous pyelography, renal ultrasonography, or spiral CT scan) and lower tracts (with cystoscopy). Persistent hematospermia (>2 mo without defined etiology) warrants a full workup as described in Workup.
Urogenital infections require appropriate antibiotic therapy, which normally resolves the problem. In all men, enterobacteria (especially Escherichia coli) should be covered. In younger men, concomitant therapy for chlamydial infections should also be used. A fluoroquinolone should adequately treat both organisms. 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 medications.
Urethral or prostatic varices are best fulgurated, while cysts, of either the seminal vesicles or prostatic urethra, can be aspirated transrectally. Fuse and colleagues injected coagulant substances into dilatated seminal vesicles under TRUS guidance in 7 patients with hematospermia. The hematospermia was transiently resolved by this maneuver for a maximum duration of 3 months, at which time the condition recurred. Therefore, currently, no evidence suggests that the injection of any substance, coagulant or sclerosant, has any role in the management of hematospermia.
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.
No rationale currently exists for the use of oral agents, such as estrogens or corticotrophins, 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.
More recently, a technique of endoscopy of the ejaculatory ducts and seminal vesicles has been described.[21, 22] This technique involves using a semirigid ureteroscope to cannulate the ejaculatory duct and allows the surgeon to examine the duct, seminal vesicle, and ampulla of the vas. However, the author reserves this technique for only the most refractory cases of hemospermia that cause significant physiologic (urinary retention or persistent hematuria) or psychological (avoidance of ejaculation) trauma.