Uro multi doc master
Ejaculatory dysfunctionand the treatment ofLUTS
Paul Sturch,Urology Department, King'sCollege Hospital, London.
For years ejaculatory dysfunction in group receiving 10mg of alfuzosin experienced no
men following medical or surgical
reduction in ejaculatory volume and there was no
treatment of lower urinary tract
significant difference in post-ejaculatory urine
symptoms (LUTS) was thought to be
sperm concentrations between the two groups
a result of disruption of the bladder
taking alpha-blockers and a placebo group [2].
neck mechanism and the subsequent
Lower doses of tamsulosin cause a lower incidence
retrograde flow of semen. Men commenced on
of ejaculatory problems and the inhibitory effect
alpha-blockers or consenting to disobstructing
on ejaculation varies between different alpha
surgery were warned of this risk of retrograde
blockers. Silodosin, a new ?1A-adrenoceptor-
ejaculation and were expected to live with it. Until
selective antagonist has been shown to cause
recently there has been little effort put into
higher rates of anejaculation than tamsulosin
challenging this perceived wisdom, even in the
(22.3% vs. 1.6%) in a study of 457 Japanese men [3].
face of the paradoxical situation of a lower
These effects are explained further in animal
Sydney Adventist HospitalClinical School, University of
incidence of ejaculatory dysfunction following
studies. Both serotonin and dopaminergic
Sydney, Australia.
bladder neck incision, which also disrupts the
receptors play an integral role in the central control
bladder neck, compared to transurethral resection
of ejaculation. Tamsulosin has a binding affinity for
of the prostate (TURP). This review seeks to address
5-HT1a and D2-like receptors almost 10,000 times
the reasons for ejaculatory dysfunction with
greater than other ? -blockers. Systemic
different LUTS / benign prostatic hyperplasia (BPH)
administration of tamsulosin has been shown to
treatments, and to comment on some new
significantly reduce bulbospongiosus contractions
developments in the field.
mediated by 8-OH-DPAT, a 5HT1a and D2-likereceptor agonist, in male rats [4].
Alpha-blockers
Alpha-blockers such as tamsulosin are the first-line
medical treatment for moderate to severe LUTS [1].
5-alpha-reductase inhibitors (5AR-I) have been
When tamsulosin was found to cause ejaculatory
shown in a number of trials to reduce prostate size,
dysfunction in up to a quarter of men, patients
improve symptom scores and flow rates and
Urology Department, King's
were initially told this was also due to retrograde
reduce the risk of urinary retention and the need
College Hospital, London.
ejaculation. This has now been shown to be a
for surgery [5]. They can be used as a monotherapy
central inhibitory effect causing anejaculation and
or in combination with alpha-blockers and are well
has little or nothing to do with the bladder neck or
tolerated. Finasteride was the first 5AR-I marketed,
Correspondence to:Gordon Muir,
backwards flow of semen. The inhibitory effect of
followed more recently by dustasteride. The
tamsulosin has been shown to be dose dependent
mechanism of action of both drugs is to inhibit the
and at 0.8mg up to 90% of subjects in one study
synthesis of dihydrotestosterone (DHT) medicated
experienced a reduction in ejaculate volume with
by the 5-alpha-reductase enzyme. Dutasetride
Declaration of competing
anejaculation in over a third. In comparison, a
inhibits the type 1 and 2 isoenzymes, reducing
It now seems clear that most ejaculatorydysfunction fol owing medical and surgicaltreatment of LUTS is not retrograde passageof semen and our surgical techniquesshould continue to develop in light of this
UROLOGY NEWS
V19(1) • NOV/DEC 2014
serum concentrations of DHT by around 90%,whereas finasteride inhibits the type 2isoenyme only, reducing serum DHT by around70% [5]. DHT is important in the embryologicaldevelopment of the male urogenital tractduring pregnancy and exposure of pregnantwomen to 5AR-Is could potentially result ingenital under development. Ingestion andabsorption though the skin should be avoidedin women of child bearing age [6]. It is advisedthat men taking a 5AR-I use condoms toprevent exposure to women via semen,although primate studies have determinedthat the potential concentrations of 5AR-I insemen are minimal [5]. Adverse effects arereported at similar rates with no statisticaldifference for both 5AR-Is. In general, 5AR-Is arewell tolerated with the most common side-effects relating to sexual dysfunction:impotence (8%), reduced libido (6%), andejaculatory dysfunction (1%) [5].
Figure 1: Endoscopic view of the prostatic fossa with preservation of the veru and surrounding tissue with pre-operative view
In 2004, Gil Vernet's group publishedenlightening evidence that bladder neckcontraction may not be necessary forantegrade ejaculation [7]. Transrectal ultrasonicimaging of 30 subjects during ejaculationthrough masturbation clearly demonstrates theantegrade propulsion of semen emitted fromthe ejaculatory ducts through the co-ordinatedcontraction of the external sphincter andbulbar urethral smooth muscle. The bladderneck is redundant in this process as there is nodiscernable retrograde flow once the ejaculate
Figure 2: the UroLift system.
Figure 3: PET monofilament suture.
is emitted from the ducts [8]. From this study, it
and surrounding ejaculatory tissue in a very
lateral lobes were carried out transurethrally
could be inferred that, as long as the tissue
similar way to the GreenLight laser technique
under general anaesthetic using the UroLift
around the verumontanum is not disrupted,
developed by the IGLU group, suggesting that
system (NeoTract Inc., Pleasanton, CA, USA)
antegrade ejaculation should still occur even
anatomy rather than energy type is of prime
(Figure 2). Outcomes were encouraging with
with an open bladder neck.
importance. The bladder neck is resected in the
the expected symptoms of haematuria and
Rather than focusing on bladder neck
same way as with standard TURP technique. By
dysuria resolved within a month of the
preservation, an increased appreciation of the
preserving apical tissue using these anatomical
operation and no patients reporting
importance of preserving the tissue
landmarks, 90% of men experienced preserved
ejaculatory dysfunction. A mean International
surrounding the verumontanum has led to
ejaculation with flowmetric parameters and
Prostate Symptom Score (IPSS) improvement
developments of ejaculation preserving
quality of life scores comparable to non-
was seen in almost all patients with a peak
surgical techniques. The International
ejaculatory preserving transurethral resection
improvement at three months of 57%. This
GreenLight Users (IGLU) group's work with
techniques [10]. In both the laser and
improvement in symptoms score receded to
anatomical and clinical data suggests that
electrosurgical approaches, the anatomical
39% improvement at one-year follow-up. One
ejaculatory duct angulation and duct
landmark of the verumontanum is used to
patient had no significant improvement and
obstruction are critical factors in maintaining
guide resection of the middle lobe to a point
went on to have a conventional TURP [6].
ejaculation following surgery with more than
1cm proximal to this level. The lateral lobes of
Similar experiences were reported in initial
85% of men in an international multicentre
the prostate are resected or vaporised to the
case series across Europe with rapid and
study retaining antegrade ejaculation after
level of the veru, without disruption of the
noticeable improvements in IPSS and peak
GreenLight laser prostatectomy. They have
paracollicular tissue (Figure 1).
urinary flow rate and without significant
suggested that even men being treated for
morbidity from operative complications or
retention of urine can have excellent functional
sexual dysfunction [11,12]. Since this early
outcomes while preserving antegrade
A new and exciting minimally invasive
experience a greater emphasis has been
ejaculation. This work has been published in
technique has recently been developed using
placed on the anterior position of the channel
video format [9]. The Neunkirchen group has
tensioning implants to hold open the
within the lumen, which has led to reduced re-
published similar data on ejaculatory
obstructing lateral lobes of the prostate into a
operation rates as the technique evolved. The
preserving TURP, which can preserve
position opening up the urethral lumen. This
technique involves the transurethral
ejaculatory function in the majority of men. The
technique was first termed the "prostatic
application of tissue-retracting polyethylene
anatomical, monopolar resection they describe
urethral lift procedure". The initial case series of
teraphthalate (PET) monofilament sutures
is focused on preserving the verumontanum
19 patients with LUTS secondary to obstructing
(Figure 3) anchored on the fibromuscluar
UROLOGY NEWS
V19(1) • NOV/DEC 2014
for Men (SHIM), Male Sexual Health Questionnaire for EjaculatoryDysfunction (MSHQ-EjD)), quality of life scores and maximum flow ratedemonstrated a rapid and sustained improvement at 1, 3 and 12 months.
No man has so far reported new ejaculatory dysfunction followingUroLift, and indeed patients treated with the urethral lift procedurereported a trend towards improvements in the ability to ejaculate, as wellas ejaculatory intensity and volume. Also, men entering the study with
pre-existing erectile dysfunction (ED) (SHIM<19) showed a small butsignificant improvement in erectile function (mean SHIM increase of 2.4points) after treatment. There was no change in erectile function in menwith normal baseline erectile function.
Conclusion
Historically, men seeking treatment for bothersome LUTS have been told
by their urologists that any methods, medical or surgical, will consign
them to dry orgasms. Many men, of all ages enjoy ejaculating and would
surely accept a reduction in treatment efficacy to preserve this importantaspect of quality of life. It now seems clear that most ejaculatorydysfunction following medical and surgical treatment of LUTS is notretrograde passage of semen, unless proven on post orgasm urinesamples, and our surgical techniques should continue to develop in lightof this. The UroLift system provides an exciting development in theminimally invasive treatment for LUTS secondary to BPH. With a relativelyshort operating time and minimal anaesthetic it has a low incidence ofadverse effects and rapid, sustained improvement in symptom scores.
This, and ejaculation preserving surgery, introduce a new qualitative
Figure 4: The implant is delivered into a prostate with encroaching lateral lobes (a), byintroducing the device under cystoscopic guidance (b), compressing the lobe with the delivery
dimension to the way we will need to counsel patients in the years
device and deploying the needle (c), retracting the needle, tensioning the monofilament to seat
ahead. Although almost no research has been carried out in the area, we
the capsular tab on the prostatic capsule and securing the connecting suture with an urethralend piece (d). Additional implants are delivered as required (e), to maintain the expanded
find that nearly all men will express strong preferences if made aware
urethral lumen (f). Images copyright NeoTract, Inc.
that LUTS / BPH treatments can impact on their ejaculatory function todifferent levels. We would encourage urologists to discuss ejaculatory
prostate capsule with a nitinol metallic tab. The implant is tensioned
dysfunction with all sexually active patients in order to allow the best
against the urethral aspect of the prostate secured with a stainless-steel
selection of treatment for an individual.
urethral end piece, compressing the glandular tissue and expanding thelumen. The implants are delivered under direct vision and placed at the 2
References
and 10 o'clock positions to avoid neurovascular bundles, the dorsal
National Institute for Health & Care Excellence CG97. Lower urinary tract symptoms. 2010.
venous complex and far away from the verumontanum. The tension in
Accessed from http://guidance.nice.org.uk
Hellstrom WJG, Sikka SC. Effects of acute treatment with tamsulosin versus alfuzosin on
the implants and elasticity of the glandular tissue combine to bury the
ejaculatory function in normal volunteers. J Urol 2006;
176:1529-33.
metal anchors reducing exposure to urine and encouraging early
Kawabe K, Yoshida M, Homma Y. Silodosin, a new α1A-adrenoceptor-selective antagonist for
treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled,
double-blind study in Japanese men. BJUI 2006;
98(5):1019-24.
Most patients can be treated using four implants, but in larger
Giuliano F. Impact of medical treatments for benign prostatic hyperplasia on sexual
prostates more may be used. (Figure 4). Emerging results from several
function. BJUI 2006;
97(Suppl 2):34-8; discussion 44-5.
multicentre studies have clearly shown the benefit of the urethral lift
Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor
dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003;
44:82-8.
procedure. Shore et al. [14], in their North American study of 51 patients,
Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of dual inhibitor of 5-alpha
showed a significant improvement in symptoms in 90% and high
reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia (BPH).
satisfaction levels with 75% of patients happy to recommend the
Saman Shafaat T, Santiago-Lastra YA, Bachmann A, et al. The impact of ejaculation-
procedure to a friend. The average procedure time was 52 minutes and
preserving photo-selective vaporization of the prostate (EP-PVP) on lower urinary tract
between two to six implants were deployed, with an average of 3.7, in
symptoms and ejaculatory function: results of a multicenter study. J Urol 2013;
189(4):e164.
prostates measuring between 30–77.3cc. In a similar, single-arm study
Gil-Vernet JM Jr, Alvarez-Vijande R, Gil-Vernet A, Gil-Vernet JM. Ejaculation in men: a dynamic
endorectal ultrasonographical study. BJU Int 1994;
73:442-8.
McNicholas et al. [13] reported a sustained symptom relief from two
weeks post procedure. In this group the progression to TURP for
Alloussi SH, Helmut S, Lang C, et al. Ejaculation-Preserving Transurethral Resection of
treatment failure was reported at 6.5%. In both studies the majority of
Prostate and Bladder Neck: Short-and Long-term Results of a New Innovative Resection
Technique. Journal of Endourology 2014;
28(1):84-9.
patients had the procedure carried out under local anaesthetic with
10. Woo HH, Chin PT, McNicholas TA, et al. Safety and feasibility of the prostatic urethral lift: a
instillation of topical lidocaine to the bladder and urethra and a sedative.
novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to
benign prostatic hyperplasia (BPH). BJU Int 2011;
108:82-8.
McVary et al. [15] randomised 206 men to receive the urethral lift or a
11. Delongchamps NB, Conquy S, Defontaines J, et al. [Intra-prostatic UroLift (®) implants for
sham procedure at a ratio of 2:1. All subjects were unblinded at three
benign prostatic hyperplasia: preliminary results of the four first cases performed in France].
months and the control patients were offered treatment options
Prog Urol 2012;
22(10):590-7.
12. Garrido AP, Coloma Del Peso A, Sinues OB, et al. [Urolift®, a new minimally invasive
including the urethral lift procedure. The prostates treated were of similar
treatment for patients with low urinary tract symptoms secondary to BPH. Preliminary
size to Shore's group but, in contrast, an average of 4.9 implants were
results.] Arch Esp Urol 2013;
66(6):584-91.
deployed in this group. The most common adverse effects were transient
13. McNicholas TA, Woo HH, Chin PT, et al. Minimally invasive prostatic urethral lift: surgical
technique and multinational experience. Eur Urol 2013;
64(2):292-9.
dysuria, haematuria and pelvic pain, experienced by both treatment and
14. Shore N, Freedman S, Gange S, et al. Prospective multi-center study elucidating patient
sham groups. At three months' follow-up a significant improvement in
experience after prostatic urethral lift. Can J Urol 2014;
21(1):7094-101.
LUTS was experienced in the treatment group compared to the controls.
15. McVary KT, Gange SN, Shore ND, et al. Treatment of LUTS secondary to BPH while
preserving sexual function: randomized controlled study of prostatic urethral lift. J Sex Med
Follow-up using validated questionnaires (IPSS, Sexual Health Inventory
UROLOGY NEWS
V19(1) • NOV/DEC 2014
Source: http://cambridgeurology.org/userfiles/UroNews%20EJD%20%20Luts%2011-2014.pdf
titolo breve: CONSENSUS ON THE USE OF CYCLOSPORINE IN DERMATOLOGICAL PRACTICE primo autore: ALTOMARE Rivista: GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIACod Rivista: G ITAL DERMATOL VENEREOL e additional copies G ITAL DERMATOL VENEREOL 2014;149:607-25 or personal or commercial use is , electronic mailing or an It is not per. aming techniques to enclose an Consensus on the use of cyclosporine
Allam Appa Rao Page 1 of 24 Professor Allam Appa Rao Allam Appa Rao Page 2 of 24 Jawaharlal Nehru Technological University: Kakinada, AP, India +91-884 2300 888 (Office), +91-884 2300 800 (Fax), +91-98481 85922 (Personal Cell) E Mails: [email protected],Web SPermanent Home Address: 4-51-19/1/2, Lawson's Bay Colony, Visakhapatnam - 530 017