Review Article

Retrograde ejaculation, painful ejaculation and hematospermia

Arie Parnham1, Ege Can Serefoglu2
1
University College London Hospitals, London, UK; 2Bagcilar Training & Research Hospital, Istanbul, Turkey
Contributions: (I) Conception and design: All authors; (II) Administrative support: EC Serefoglu; (III) Provision of study materials or patients: None;
(IV) Collection and assembly of data: None; (V) Data analysis and interpretation: A Parnham; (VI) Manuscript writing: All authors; (VII) Final
approval of manuscript: All authors.
Correspondence to: Ege Can Serefoglu, MD, FECSM. Cinnah Caddesi No. 47, 06680, Cankaya, Ankara, Turkey. Email: [email protected].

Abstract: Although there has been an increased interest on premature ejaculation in the recent years, our
understanding regarding the disorders of retrograde ejaculation, painful ejaculation and hematospermia
remain limited. All three of these conditions require a keen clinical acumen and willingness to engage in
thinking outside of the standard established treatment paradigm. The development of novel investigational
techniques and treatments has led to progress in the management of these conditions symptoms; however,
the literature almost uniformly is limited to small series and rare randomised trials. Further investigation and
randomised controlled trials are needed for progress in these often challenging cases.

Keywords: Dysorgasmia; ejaculatory dysfunction; ejaculatory pain; hematospermia; painful ejaculation; retrograde
ejaculation

Submitted Apr 28, 2016. Accepted for publication Apr 28, 2016.
doi: 10.21037/tau.2016.06.05
View this article at: http://dx.doi.org/10.21037/tau.2016.06.05

Introduction their partner especially when trying to conceive (3).

The process of ejaculation requires complex co-ordination
Although there has been an increased interest in premature
and interplay between the epidiymides, vasa deferentia,
ejaculation since the introduction of the first oral compound
prostate, seminal vesicles, bladder neck and bulbourethral
developed specially for the treatment of this problem in
glands (4). Upon ejaculation, sperm are rapidly conveyed
2006 (1), our understanding regarding the disorders of
along the vas deferens and into the urethra via the
retrograde ejaculation, painful ejaculation and hematospermia ejaculatory ducts. From there, the semen progresses in an
remain limited. antegrade fashion in part maintained by coaptation of the
In this article, we will summarize the possible etiologic bladder neck and rhythmic contraction of the periurethral
factors related to these ejaculatory problems and their muscles co-ordinated by a centrally mediated reflex. Closure
management will be reviewed in light of the current literature. of the bladder neck and seminal emission are initiated
via the sympathetic nervous system from the lumbar
Retrograde ejaculation sympathetic ganglia and subsequently hypogastric nerve.
Prostatic and seminal vesicle secretion as well as contraction
Ejaculation is an essential step in normal human reproduction of the bulbocavernosal, ischiocavernosal and pelvic floor are
and its failure leads to infertility. Many ejaculatory disorders initiated by the S2-4 parasympathetic nervous system via
can have both psychological as well as organic causes; the pelvic nerve.
however, retrograde ejaculation is unique in that as it is almost Any factor, which disrupts this reflex and inhibits the
exclusively organic in origin. Despite being a common type of bladder neck (internal vesical sphincter) contraction, may
ejaculatory dysfunction, it is responsible for only 0.3–2% of lead to retrograde passage of semen into the bladder. These
infertility (2). The combination of dry orgasm and issue with can be broadly categorised as pharmacological, neurogenic
fertility make the condition distressing to both patient and or anatomic causes of retrograde ejaculation (Table 1).

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Translational Andrology and Urology, Vol 5, No 4 August 2016 593

Table 1 Causes of retrograde ejaculation

Category Cause
Pharmacological Alpha-adrenergic blockers
Psychotropic medications
Neurogenic Spinal cord injuries
Lumbar sympathectomy
Retroperitoneal lymph node dissection (RPLND)
Aorto-iliac vascular surgery
Abdominoperineal resection
Diabetic autonomic neuropathy
Multiple sclerosis
Myelodysplasia
CVA
Anatomical
Congenital Posterior urethral valves, utricular cysts and extrophy
Acquired Transurethral bladder neck incision
Transurethral resection of prostate
CVA, cerebrovascular accident.

Men with retrograde ejaculation have little to suggest after orgasm in patients with retrograde ejaculation (9).
a diagnosis in terms of symptoms beyond that of reduced McMahon et al. recommended that the post-orgasmic
ejaculation or dry orgasm. Post orgasm, many men will urine should be centrifuged and the visualization of 10–15
describe the passage of cloudy urine. This can be attributed sperm per high-power field would confirm the diagnosis
to the mixing of semen in the bladder with urine. A number of retrograde ejaculation (10) whereas Fedder et al.
of men will present with fertility issues for the obvious defined retrograde ejaculation as more than one million
reasons (5). A thorough history should focus on the timing spermatozoa found in a post-ejaculatory urine sample (5).
and symptoms as well as identifying the underlying cause. Medical and surgical strategies exist for the treatment
The lower reference limit for semen volume is 1.5 mL of retrograde ejaculation. In recent years the reliance of
[5th centile, 95% confidence interval (CI) 1.4–1.7] as medical treatment as first line management has become
defined by the World Health Organisation (6). Men with common practice. Sympathomimetics stimulate the
values below this are considered to have hypospermia release of noradrenaline as well as activating alpha- and
whilst those with complete absence of ejaculate are defined beta-adrenergic receptors, resulting in closure of the
as aspermic. These terms should not be confused with internal urethral sphincter, restoring antegrade flow
oligozoospermia and azoospermia that indicate reduced of semen. The most common sympathomimetics are
sperm counts but can have a normal semen volume. synephrine, pseudoephedrine hydrochloride, ephedrine,
Hypospermia, as defined by the National Institute of phenylpropanolamine and midrodrine. Unfortunately as
Health, is a condition when a semen volume lower than time progresses their effect diminishes (11). Many of the
2 mL is recorded on at least two semen analyses (7). studies published about the efficacy of sympathomimetics
Hypospermia or aspermia should highlight to the clinician in the treatment of retrograde ejaculation suffer from small
the possibility of retrograde ejaculation. The presence of sample size with some represented by case reports.
either though cannot differentiate between a disorder of A double blind controlled study randomised patients to
emission and true retrograde ejaculation. one of four alpha-adrenergic agents (dextroamphetamine,
Consequently, Vroege et al. suggested that the analysis ephedrine, phenylpropanolamine and pseudoephedrine)
and confirmation of sperm in a post orgasmic urine with or without histamine. The patients suffered
sample could help differentiate between these two separate from failure of ejaculation following retroperitoneal
disorders (8). Fructose can also be found in the urine analysis lymphadenectomy. They found that 4 days of treatment

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594 Parnham and Serefoglu. Retrograde ejaculation, painful ejaculation & hematospermia

prior to ejaculation was most effective and that all the techniques. A systematic review of the literature
adrenergic agonists restored antegrade ejaculation (12). in couples with the male partner suffering from
In a systematic review, the efficacy of this group of retrograde ejaculation found a 15% pregnancy rate
medications was found to be 28% (2). The side effects of per cycle (0–100%) based on 15 articles (2);
sympathomimetics include dryness of mucous membranes (II) Hotchkiss method: the Hotchkiss and modified
and hypertension. Hotchkiss method involves emptying the bladder
The use of antimuscarinics has been described, including prior to ejaculation using a catheter and then
brompheniramine maleate and imipramine, as well as washing out and instilling a small quantity
in combination with sympathomimetics. The calculated of Lactated Ringers to improve the ambient
efficacy of antimuscarinics or antimuscariics in combination conditions of the bladder. The patient then
with sympathomimetics are 22% vs. 39% respectively (2). ejaculates and semen is retrieved by catheterisation
Combination therapy appears to be more effective although or voiding (16). Modified Hotchkiss methods
statistical analysis is not yet possible due to the small sample involve a variance in the instillation medium.
sizes. Pregnancy rates per cycle were 24% per cycle
Bladder neck reconstruction has also been suggested for (0–100%) based on eight papers (2);
the treatment of retrograde ejaculation. Abrahams described (III) Ejaculation on a full bladder: few papers have
the use of a V-Y plasty of the bladder neck in two patients described results from this technique (17,18). The
who subsequently regained antegrade ejaculatory function patient is encouraged to ejaculate on a full bladder
and one went on to father a child (13). Similarly, Middleton and semen is suspended in Baker’s buffer. The
and Urry used the Young-Dees type of bladder neck pregnancy rate in the two studies which included
reconstruction and were able to restore normal antegrade only five patients in total was 60% (2).
ejaculation in 4 out of 5 patients (14). Other surgical or
interventional techniques have included injecting collagen
Painful ejaculation
into the bladder neck and the use of surgical sperm retrieval
to achieve pregnancy (15). Painful ejaculation (also known as dysejaculation,
Infertility has been the major concern of patients with odynorgasmia, post orgasmic pain, dysorgasmia or
retrograde ejaculation. Beyond the use of standard sperm orgasmalgia) is a common but poorly understood clinical
retrieval techniques such as TESE and PESA, three phenomenon, which is associated with sexual dysfunction.
different methods of sperm retrieval have been identified Several studies demonstrated its prevalence in between
for the management of infertility in the patient suffering 1–10% in the general population (19-21); however, it may
from retrograde ejaculation. These include; centrifugation increase to 30–75% among men who suffer from chronic
and resuspension of post ejaculatory urine specimens, prostatitis/chronic pelvic pain syndrome (CP/CPPS) (22-26).
the Hotchkiss (or modified Hotchkiss) technique and It should be noted that the design of the majority of these
ejaculation on a full bladder: papers is not scientifically sound and the condition is
(I) Centrifugation and resuspension: in order to probably underreported due to the lack of an evidence-
improve the ambient conditions for the sperm, based definition and well-defined prognostic criteria.
the patient is asked to either increase their fluid The severity of painful ejaculations may vary from a
intake or to take sodium bicarbonate to dilute minor discomfort to excruciating pain (27-31). It may occur
or alkalise the urine respectively. Afterwards, a anywhere in the pudendal territory, including penis, scrotum
post orgasmic urine sample is collected by either and perineal/perianal region (27-29,31-36). The pain
introducing a catheter or spontaneous voiding. typically initiates immediately before or during ejaculation
This sample is then centrifuged and suspended in a and commonly lasts between 2 to 24 hours (32,33). This
medium. The types of suspension fluids employed problem may reduce the individual’s self-esteem and sexual
are heterogeneous and can include bovine serum desire, which could well result in a decrease quality of life (37).
albumin, human serum albumin, Earle’s/Hank’s, Many medical conditions can result in painful
phosphate buffered medium and the patients urine ejaculations but it can also be an idiopathic problem.
to name but a few. The resultant modified sperm Initial reports demonstrated possible associations of
mixture can then be used in assisted reproductive painful ejaculation with calculi in the seminal vesicles,

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Translational Andrology and Urology, Vol 5, No 4 August 2016 595

sexual neurasthenia, sexually transmitted diseases (38-40) scans are rarely required. Magnetic resonance imaging
antidepressants (28,29,41,42), inflammation of prostate studies may be helpful when investigating the cause of
(25,43), prostate cancer (44,45), benign prostatic hyperplasia pudendal neuropathy. However, no obvious aetiology is
(23,46-49), prostate surgery (50,51), pelvic radiation (52) found in a significant number of patients with the complaint
and herniorrhaphy (27,30,34,53) amongst others. of painful ejaculations, despite extensive investigation (62).
Psychological issues may also be the cause of painful Treatment of painful ejaculation must be tailored
ejaculations, especially if the patient does not experience this according to the underlying cause, if detected.
problem during masturbation (54-56). Several case reports Psychotherapy or relationship counselling, withdrawal of
have suggested that mercury toxicity or ciguatera toxin fish suspected agents (drugs, toxins, or radiation) (28,29,41,42)
poisoning may also result in painful ejaculations (57-59). or the prescription of appropriate medical treatment
Common to all sexual problems, the assessment of a (antibiotics, α-blockers, anti-inflammatory agents) may
patient with painful ejaculation must start with a rigorous ameliorate painful ejaculations (63). If medical treatments
medical and sexual history. Such a history should relate fail, surgical operations such as transurethral resection of the
to the following as a minimum-relationship issues, prostate, transurethral resection of the ejaculatory duct and
psychological problems, sexually transmitted diseases, neurolysis of the pudendal nerve may be necessary (64-66).
drug intake, urinary symptoms, prostatic diseases (e.g., Behavioural therapies, myorelaxant, antidepressant pelvic
prostatitis, CP/CPPS), familial prostate cancer, previous floor exercises, anticonvulsant drugs and/or opioids may be
surgical procedures (e.g., groin herniorrhaphy, radical administered if no underlying cause can be identified (67,68).
prostatectomy) and radiotherapy must be recorded.
Several questionnaires have been developed and should
Hemospermia
be ideally be administered—such as Beck depression and
anxiety scales, International Prostatic Symptom Score The presence of blood in the semen can cause the patient
(IPSS), National Institute of Health-Chronic Prostatitis significant anxiety although it is considered by many
Symptom Index (NIH-CPSI). These will assist the professionals to be a self-limiting and usually benign
physician in ascertaining the underlying patient condition condition (69,70). Comments on the symptom have been
at an early stage. The type and location of the pain (visceral passed by notaries including Hippocrates, Galen, Pare,
neuropathic or somatic) must be recorded (60) along with Morgagni, and Fournier (69). The few articles that exist
those circumstances which aggravate and relieve pain. in the literature are limited mainly to case reports and
A focused physical examination may disclose scars from cohort series. Consequently, there is little to recommend a
previous surgeries or radiotherapy in the groin area whereas definitive diagnostic or management strategy.
pathognomonic dermal lesions and purulent urethral The definition of hemospermia is the presence of blood
discharge may be suggestive of sexually transmitted diseases. in the ejaculate. Further classification is not mentioned in
Palpation of a swollen and painful prostate during digital the literature and there is no distinction between visible and
rectal examination (DRE) is a diagnostic finding for acute non-visible hemospermia.
prostatitis whereas a nodule can be felt in the presence The exact incidence and prevalence of hemospermia is
of a prostate cancer. A neurological and musculoskeletal difficult to elucidate due to a number of factors including its
examination may detect pudendal neuropathy which is covert presentation, usually self-limiting nature and patient
caused by pudendal nerve entrapment, pudendal canal embarrassment. The symptom represents approximately
syndrome or pudendal neuralgia (61). 1–1.5% of all urological referrals and occurs in all age groups
Laboratory tests should be focused on symptoms. Direct with a mean age of 37 (69,71). It is usually a self-limiting
microscopic examination of the urethral discharge and condition with an average duration of 1–24 months (69,70).
urethral culture may be beneficial in assigning the type of In a prostate cancer screening study of 26,126 men, 50 years
the bacteria, which causes urethritis. Similarly, a 4-cup test and older or older than 40 with a history of prostate cancer
may confirm the location of urinary infection and confirm or of black race, hemospermia was found in 0.5% on entry
the diagnosis of prostatitis. to the trial (72).
Serum prostate specific antigen levels may also suggest A number of causes of hematospermia have been
pathology within the prostate (i.e., prostatitis and/or identified but can be broadly classified into the following
prostate cancer). Abdominal computerized tomography sub-categories; idiopathic, congenital malformations,

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596 Parnham and Serefoglu. Retrograde ejaculation, painful ejaculation & hematospermia

Table 2 Causes of hematospermia (73)

Category Causes

Congenital Seminal vesicle or ejaculatory duct cysts

Inflammatory Urethritis, prostatitis, epididymitis, tuberculosis, CMV, HIV, schistosomiasis, hydatid, condylomata of urethra and
meatus, urinary tract infection

Obstruction Prostatic/seminal vesicle/ejaculatory duct calculi, post inflammatory, seminal vesicle diverticula/cyst, urethral
stricture, utricle cyst, benign prostatic hypertrophy

Malignancy Prostate, bladder, seminal vesicle, urethra, testis, epididymis, melanoma

Vascular Prostatic varices, prostatic telangiectasia, haemangioma, posterior urethral veins, excessive sex or masturbation

Trauma/iatrogenic Perineum, testicle, instrumentation, post haemorrhoid injection, prostate biopsy, vaso-venous fistula

Systemic Hypertension, haemophilia, purpura, scurvy, bleeding disorders, chronic liver disease, renovascular disease,
leukaemia, lymphoma, cirrhosis, amyloidosis

CMV, cytomegalovirus; HIV, human immunodeficiency virus.

inflammatory conditions, obstruction, malignancies, should be noted along with the age and if it is recurrent or
vascular abnormalities, iatrogenic/trauma and systemic isolated.
causes (Table 2). Associated features should also be elicited including
The risk of any malignancy in patients presenting with lower urinary tract symptoms (LUTS), concomitant
hematospermia is on average 3.5% (range, 0–13.1%) (74). haematuria and testicular/penile pain. A sexual history
In an observational study of 300 consecutive patients over a should be taken to identify those whose hematospermia
30-month period, 81% had no cause of their hematospermia may be as a consequence of a sexually transmitted disease.
identified. In those patients for whom a cause was identified, Recent foreign travel to areas affected by schistosomiasis
the diagnosis varied dependent upon the age of presentation. or tuberculosis should also be considered. The possibility
When the patients were divided into those under and over of co-existing systemic disease such as hypertension, liver
40 years of age, urinary tract infections were more common disease and coagulopathies should be investigated along
among younger patients vs. older patients (15% vs. 10.3%). with systemic features of malignancy such as weight loss,
In the older group (>40 years old), stones (2.2% vs. 1.4%) loss of appetite or bony pain.
and malignancy (6.2% vs. 1.4%) were more common Examination of the patient should include measurement
when compared with the younger cohort (71). In the over of the blood pressure, as there have been a number of case
40 group, 13 patients had prostate cancer and 1 had a low-grade reports suggesting an association between uncontrolled
urethral carcinoma. In the under 40 group, 1 patient had hypertension and hematospermia (77,78). The abdomen
testicular cancer (71). should be examined for masses and organomegaly. A
The investigation of hematospermia should begin with a thorough groin, perineal, and genital examination should be
thorough symptom specific and systemic clinical history— performed including the urethral meatus.
accompanied by examination of the patient. The first step is DRE should also be performed, and the meatus
to establish if the patient has true hematospermia. Pseudo- re-examined after DRE for the presence of bloody
hematospermia can be as a consequence of haematuria or discharge (79). Detection of a palpable nodule in the prostate
even suction of a partner’s blood into the urethra during is of importance as an association between hematospermia
copulation. This can be excluded by performing a condom and prostate cancer has been postulated although not
test and the semen visually examined. Melanospermia that completely proven. A community-based prostate screening
is a consequence of malignant melanoma involving the study was undertaken of 26,126 men over 50 (or older than
genitourinary tract has also been described in a two case 40 with a family history of prostate cancer of black American
reports (75,76). Chromatography of the semen sample can heritage) who underwent PSA testing and DRE at 6 monthly
be used to distinguish the two by identifying the presence or yearly intervals. At each visit they were asked about the
of melanin. The volume, colour, duration and frequency presence of hemospermia, haematuria and LUTS. Patients

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Translational Andrology and Urology, Vol 5, No 4 August 2016 597

with a raised PSA underwent transrectal ultrasound (TRUS) in 82–95% of men with hematospermia (70,84-88).
guided prostate biopsy. In the overall screening population, In a recent study of 115 patients presenting with
a significantly higher number of patient with hemospermia hematospermia, all patients had a benign finding on TRUS
were found to have prostate cancer compared with those (85.2% had calcification, 7% hypoechoic area, 30.4% had
that did not have hemospermia (13.7% vs. 6.5%) (72). a seminal vesical abnormality) (89). Earlier studies by Yagci
The same held true when men with hemospermia and et al. and Zhao et al. had similar findings with abnormalities
prostate cancer were matched with those diagnosed with found in 94.5% and 94.8% respectively in men referred for
prostate cancer and no hemospermia (P=0.035) (72). hematospermia (85).
On multivariate logistic regression modelling, after MRI is being increasingly used as a definitive means to
adjusting for age, PSA and DRE, hemospermia was investigate hematospermia. The multiplanar ability of MRI
predictive of prostate cancer although narrowly missed to accurately represent structural changes in the prostate,
significance (72). The fact that this study though was part of seminal vesicles, ampulla of vas deferens, and ejaculatory
a prostate-screening group suggests that the results should duct has enabled the modality to be particularly useful in
be interpreted cautiously due to the risk of bias. determining the organ of origin of midline or paramedian
Most authors that propose an investigative baseline agree prostatic cysts and in determining optimal surgical
on the initial diagnostic tests, however there is no consensus management (90-94). The addition of an endorectal coil
statement in this regards (73,74,80,81). can improve the diagnostic accuracy for identifying the site
A urinalysis should be taken along with sending the and case of haemorrhage (90, 91,94).
urine for culture and sensitivities as well as microscopy. The use of cystoscopy has been included in the majority
If tuberculosis or schistosomiasis is suspected, the semen of suggested investigation protocols in patients with
or prostatic secretions should be sent for analysis. A full high-risk features. It can provide invaluable information
sexually transmitted disease screen including first void urine as it allows direct visualisation of the main structures
as well as serum and genitourinary samples should be taken in the urinary tract that can be attributed to causes of
and tested for chlamydia, ureaplasma and herpes simplex. hematospermia such as polyps, urethritis, prostatic cysts,
Using this strategy, it may be possible to find an infectious foreign bodies, calcifications and vascular abnormalities (74).
agent among patients who would have been labelled as With the advancement of optics the ability to create
idiopathic hematospermia (82). ureteroscopes of diameters small enough to allow insertion
A serum PSA should be taken in men over the age of into the ejaculatory duct and seminal vesicles has been
40 who have been appropriately counselled as previously made possible. The first attempt to use a ureteroscope to
mentioned (72). Blood work including a full blood count, directly visualise the seminal vesical was performed in 1997
liver function tests, and a clotting screen should be taken to investigate a fistula (95).
to identify systemic diseases as per Table 2. The question Subsequently a number of articles have been submitted
of whether further investigation is warranted depends on examining the diagnostic and therapeutic advantages of this
clinician judgement, patient age and an assessment of risk approach (96-101). In a prospective study of 106 patients
factors (73). with prolonged hematospermia patients underwent both
Prior to the widespread accessibility of TRUS, MRI and TRUS and seminal vesiculoscopy. With both modalities
CT, the standard imaging was a plain X-ray KUB and an combined, diagnoses were made in 87.7% of patients.
excretory intravenous urogram. However, these modern When compared, head-to-head, the diagnostic yield for
imaging modalities are more sensitive in diagnosis of TRUS vs. seminal vesiculoscopy was 45.3% vs. 74.5%
malignant disease (83). TRUS is now widely accepted as the respectively (P<0.001) (102).
first imaging modality in men presenting with risk features.
It is relatively cheap, accessible and enables real-time cross
Conclusions
sectional imaging. TRUS is able to identify stones in the
seminal vesicles, prostate and ejaculatory ducts, and soft All three of the conditions that have been explored in this
tissue masses such as polyps and tumour. Further biopsy of article require a keen clinical acumen and willingness to
any soft tissue abnormalities can also be taken at the time. engage in thinking outside of the standard established
There are a number of papers that recommend its use treatment paradigm. The development of novel
and have suggested that it can demonstrate an abnormality investigational techniques and treatments has led to

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598 Parnham and Serefoglu. Retrograde ejaculation, painful ejaculation & hematospermia

progress in the management of these conditions symptoms; 2016;692-708.

however, the literature almost uniformly is limited to small 11. Gilja I, Parazajder J, Radej M, et al. Retrograde ejaculation
series and rare randomised trials. Further investigation and and loss of emission: possibilities of conservative treatment.
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drugs on post-lymphadenectomy aspermia. J Urol
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Acknowledgements
13. Abrahams JI, Solish GI, Boorjian P, et al. The
None. surgical correction of retrograde ejaculation. J Urol
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14. Middleton RG, Urry RL. The Young-Dees operation
Footnote
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Conflicts of Interest: The authors have no conflicts of interest 1986;136:1208-9.
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collagen injection restores antegrade ejaculation after
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Cite this article as: Parnham A, Serefoglu EC. Retrograde

ejaculation, painful ejaculation and hematospermia. Transl
Androl Urol 2016;5(4):592-601. doi: 10.21037/tau.2016.06.05

© Translational Andrology and Urology. All rights reserved. tau.amegroups.com Transl Androl Urol 2016;5(4):592-601