Hematospermia

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.

Conditions of the prostate

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]

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. ^[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%).

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 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

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]

Accidental and surgical trauma

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

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:

• Severe uncontrolled hypertension
• Elevated serum creatinine levels
• Severe  proteinuria
• Renovascular disease

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]

Frequency

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]

Age

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]