Testosterone supplementation improves sexual life in the aging male

An article recently published on "The Journal of Clinical Endocrinology & Metabolism", a very prestigious International Journal, confirms that testosterone supplementation improves sexual life and sex drive in the aging male. Testosterone, which is mainly produced in the testicles, represents the main male sexual hormone.

This article, written by eminent Authors, is based on a placebo-controlled study, which has analysed a sample of 470 men. All patients were more than 65 years old and had low levels of serum testosterone (less than 275 ng/dL). All patients complained of sexual dysfunction and of low sex drive.

All patients were randomized to take either testosterone gel or placebo on a daily basis for one year and have been assessed on three monthly intervals with the administration of validated questionnaires in order to assess erectile function and sex drive.

The results of this study have shown that patients who have been administered testosterone gel have shown a significant improvement in the quality of erections and in sex drive.

The results of this study therefore confirm the importance of testosterone in maintaining an adequate sexual life in the aging male.

It remains paramount that the choice of administering testosterone in patients with low levels of this hormone should be always based on a thorough clinical assessment of the patient and on an evaluation of risks and benefits.

Obstructive azoospermia: what can be done?

Azoospermia can be defined as the absence of spermatozoa in the seminal fluid and/or in the urine after ejaculation and can be subdivided into the obstructive and non-obstructive subtypes. Obstructive azoospermia (OA) represents only 15-20% of all cases of azoospermia and is characterised by the presence of a blockage, which does not allow the spermatozoa to make their way out in the seminal fluid. 

In order to fully understand obstructive azoospermia, it is important to know the pathway spermatozoa have to take from the testicle in order to reach the ejaculate. 

Spermatozoa are produced in the testicle and reach the epididymis through small tubules that join together to form a single larger tubule which coils on its own to form the body and tail of the epididymis itself. The full length of this tubule is around 7 meters. The epididymis is then connected to the prostate and the urethra through a conduit approximatively 40 cm long, which is called vas deferens. Before entering the urethra, the vas deferens joins the duct of the seminal vesicle to form the ejaculatory duct. 

Prostate and seminal vesicles produce a thick whitish fluid, called seminal fluid, which mixes with the spermatozoa to form the semen. 

Obstruction at any point can cause obstructive azoospermia. 

According to the location of the blockage, obstructive azoospermia can be subdivided into:

1)     Intra-testicular obstruction (15% of cases)

2)     Epididymal obstruction (30-70% of cases)

3)     Obstruction of the vas deferens (5-10% of cases)

4)     Ejaculatory duct obstruction ( 3-5% of cases)

If the obstruction is intra-testicular or at the level of the head of the epididymis, surgical recanalisation is not possible and therefore intra-testicular sperm extraction (TESE) is the only solution to retrieve spermatozoa.

In case of obstruction of the epididymis, although sperm retrieval is possible with a percutaneous epididymal sperm aspiration (PESA), with a microsurgical epididymal sperm aspiration (MESA) or with a TESE, in many cases it is possible to perform a microsurgical reconstruction to bypass the obstructed site and allow the spermatozoa to flow back into the ejaculate. This complex microsurgical procedure is called tubulo-vasostomy and involves connecting the vas deferens with the body of the epididymis. Due to its complexity, success rate of this procedure is around 50%.

Obstruction of the vas deferens is in most cases secondary to previous vasectomy or inguinal hernia repair, and can be corrected with a vaso-vasostomy procedure. This microsurgical technique involves excising the obstructed segment of vas and connecting back together the two ends of the vas. Although complex, in expert hands this procedure has very high success rates.

Ejaculatory duct obstruction can be caused by the presence of stones inside the duct or by external compression caused by a midline prostatic cyst. Stones can be usually washed away flushing the seminal vesicles under ultrasound guidance while prostatic cysts can be resected endoscopically reliving the compression of the ejaculatory ducts. If the last portion of the ejaculatory ducts is obstructed, this can be resected off endoscopically with a procedure called transurethral resection of the ejaculatory ducts (TURED).

In conclusion, although in many cases of obstructive azoospermia testicular/epididymal sperm extraction represents the only solution for patients wishing to father a child, microsurgical reconstruction that allows to bypass the obstruction is possible and should be offered to carefully selected patients. If successful, these reconstructive procedures will allow the couple to father a child naturally. 

Medical treatment for Peyronie's Disease. What does actually work?

Medical therapy in Peyronie's Disease can play a role both in the acute and chronic phase of the condition.

In the acute phase, the aim of medical therapy is to promote a quicker resolution of pain and inflammation in order to improve patient's quality of life and minimize the damage in terms of deformity and penile shortening produced by the plaque. In other words, during this phase, medical treatment should be offered to limit the potential progression of Peyronie's Disease so that surgery may not be needed, and if required, less invasive forms of surgical procedures can be offered to correct the deformity.

In the chronic phase of Peyronie's Disease, once the inflammatory process has settled and the curvature has stabilized, the aim of medical therapy is to reduce the degree of deformity and/or improve the quality of the erections in patients with a degree of erectile dysfunction.

It is paramount to keep in mind that around 9% of patients with Peyronie's Disease will notice a progressive reduction in the severity of their penile deformity, and that as a general role, any form of treatment is indicated only when the deformity and/or the worsening of the quality of the erections renders penetrative sexual intercourse uncomfortable or impossible.

Unfortunately none of the conservative treatment options will work for every patient and therefore a  multi-modal approach should be always advised and should be tailored to the unique indiidual profile of each patient.

With the exception of injection of Collagenase Clostridium Histolyticum, patients need to be aware that benefits of medical treatment during the chronic phase of Peyronie's Disease are minimal.

Oral Medication for Peyronie’s Disease

Although a large number of oral medications and supplements have been proposed over the years for the treatment of Peyronie’s Disease, none of these have shown a significant therapeutic benefit when compared with placebo.

The most common oral treatments for Peyronie's Disease are reported:

Vitamin E and propionyl-L-carnitine in isolation and combination (Supplement)

Vitamin E and propionyl-L-carnitine in isolation and combination have proven to be completely ineffective for the treatment of Peyronie's Disease.

Colchicine (Prescription drug)

Colchicine is an anti-gout agent that prevents the deposition of scar tissue ad therefore has been prescribed to patients affected by Peyronie's Disease with the aim to minimize scar formation. However, there is no clinical evidence that the administration of Colchicine has any role in limiting the progression of Peyronie's Disease.

Potassium aminobenzoate – POTABA (Prescription drug)

Although POTABA may play a minor role in inhibiting the progression of the plaques, it is also associated with severe gastrointestinal side effects and therefore it is not recommended.

Tamoxifen citrate (Prescription drug)

This is another compound that may potentially inhibit scar formation but there is no clinical evidence of any benefit in patients with Peyronie’s Disease.

Pentoxifylline (Prescription drug)

Pentoxifylline administration may result in a moderate reduction in plaque size and in penile curvature. The cost of the medication is relatively low and although there are some potential side effects, it is one of the treatments that patients can try during the acute phase of Peyronie’s Disease with the aim to reduce progression.

Coenzyme Q10 and Acetyl-L-carnitine (Supplement)

Coenzyme Q10 and Acetyl-L-carnitine administration during the acute phase of Peyronie's Disease may inhibit disease progression. However further studies are required to see whether these two supplements are really effective in this group of patients.

 

Phosphodiesterase type 5 inhibitors

 

Phosphodiesterase type 5 inhibitors (PDE5i) such as Viagra, Cialis and Levitra may also play a role both in the acute and chronic phase of Peyronie's Disease. During the acute phase these medications, by increasing the strength of erections, provide a good stretch to the plaque and may play a role in limiting the potential progression of the disease and minimizing the degree of penile shortening. Furthermore, PDE5i may play locally a role at the level of the plaque by inhibiting the deposition of scar tissue. In the chronic phase of Peyronie's Disease instead, PDE5i may be useful in patients with a degree of erectile dysfunction in order to guarantee the rigidity necessary to engage in penetrative sexual intercourse.

Injection Therapy for Peyronie’s Disease

Intralesional injections of a variety of medications have been proposed in patients with Peyronie’s disease. Over the years, the most commonly injected medication has been Verapamil but there is no evidence of any significant benefit in patients with Peyronie's Disease and therefore this practice should be discouraged.

Initial medical trials of intralesional injections of Collagenase Clostridium Histolyticum (Xiapex in Europe, Xiaflex in the USA) have shown promising results and it is currently the only FDA (the government body responsible for approving drugs in the US) approved medical treatment for Peyronie’s disease.

Xiaflex injections are already prescribed to treat Dupuytren’s contracture of the palmar fascia, as this drug works by breaking down the collagen present in the scar tissue of the plaque.

Currently injections of Xiapex are indicated only for patients with dorsal and dorsolateral curvatures. Xiapex injections in ventral plaques are not recommended in order to avoid potential urethral injury. Injections should also not be offered to patients with large calcified plaques due to the risk of rupture of the needle in the hardened plaque.  

Patients need to be counselled that administration of Xiapex injections may produce a reduction of the curvature of around 20-30% but not a complete correction of the deformity. This degree of correction may not be particularly useful in patients with severe curvatures, as a patient with 90 degrees of curvature may expect to get down to around 60 degrees at the end of the cycle of injections, but may  allow patients with a moderate curvature to avoid surgery.

Extracorporeal shock wave treatment (ESWT) for Peyronie’s Disease

There is no evidence that ESWT is beneficial in reducing the degree of curvature in patients with Peyronie's Disease although there is some evidence that it may reduce pain at the level of the plaque during the active phase of the disease. Therefore, ESWT should not be considered an effective treatment option for Peyronie’s Disease.

Traction and vacuum devices for Peyronie’s Disease

The aim of the application of continuous traction (using either a stretching device or a vacuum constriction device) for Peyronie’s disease is to increase the activity of degradative enzymes, which in turn leads to a loss of tensile strength and ultimately to plaque solubilisation.

Furthermore, a regular stretching may counteract the contracture due to scarring formation and may therefore reduce the progression of the curvature and the extent of penile shortening.

The main limit of traction therapy is that to be effective it needs to be continued for many hours on a daily basis and this may not be feasible for many patients.

What is Peyronie's Disease?

Peyronie's Disease, also known as Induratio Penis Plastica was initially described by the French Surgeon Francois Gigot de La Peyronie in 1743.

It represents a disorder of the tunica albuginea of the penis, which is the connective layer surrounding the erectile tissue of the corpora cavernosa. 

Peyronie's Disease is characterized by the formation of a scar, commonly known as "plaque", which can be appreciated during examination of the penis. Since scar tissue is inelastic and does not stretch as the surrounding tunica albuginea, during erections it will cause a traction of the corpora cavernosa, bending them in the direction of the plaque. The degree of deformity varies according to the size, shape and texture of the plaque and in many cases can be so severe to interfere with penetrative sexual intercourse. 

Cardiovascular risk factors are often present in patients with Peyronie's Disease and erectile dysfunction is therefore not uncommon. Alternatively, erectile dysfunction can be caused by Peyronie's Disease itself, especially when the plaque produces a hourglass deformity or when it directly infiltrates the cavernosal arteries. It has also been suggested that the plaque can cause venous leak and ultimately erectile dysfunction as it disrupts the normal interface between cavernosal smooth muscle and tunica albuginea.

Peyronie's Disease is a relatively common condition, with a prevalence of around 10% in men of 50-70 years of age. Although the onset of this condition is typically in the fifth decade of life, cases of Peyronie's Disease have been described in all age groups. Typically Peyronie's Disease tends to be more aggressive in the younger patient.

Although the real cause of Peyronie's Disease is still not completely clear, it is believed that this condition represents a wound healing disorder and that plaque formation is consequence of penile trauma in the genetically susceptible patient.

Peyronie's Disease is typically characterized by two separate phases. The first phase, also known as inflammatory phase, due to the presence of a local inflammatory process that will lead to the formation of the plaque, usually lasts around 6-9 months. During this phase many patients complain of pain during erections, when the plaque is under tension, while penile deformity worsens with the increase in size of the plaque. At the end of this phase the inflammation settles and the plaque stabilizes. Once the inflammation disappears, the pain during erections progressively settles and the deformity stabilizes. This represents the chronic phase of Peyronie's Disease.

Diagnosis of Peyronie's Disease relies mainly on history taking and physical examination. An adequate assessment of the quality of the erections and of the degree of deformity and shortening of the penis once the disease has stabilized is necessary in order to formulate the most appropriate treatment plan.  

Implantation of three pieces inflatable penile prosthesis in patients with refractory erectile dysfunction

At present, patients with erectile dysfunction non responsive to oral medications and intracavernosal injection therapy are best served with penile prosthesis implantation.  

Among the various types of penile prosthesis available, the best results are achieved after the implantation of three pieces inflatable penile prosthesis as they guarantee a more natural erection and better girth and rigidity than their semirigid counterpart. 

Three pieces inflatable penile prosthesis are formed by 2 cylinders, which will be placed inside the corpora cavernosa of the penis, a pump, usually located in the scrotum between the testicles, and an intra-abdominal reservoir.  The components of the implant are connected by small tubing and all the system is filled with sterile water.

In most cases the device can be inserted though a 3 cm long incision at the root of the scrotum. This approach guarantees enough exposure to allow the surgeon to place the cylinders, the pump and the reservoir.

Classically the reservoir is positioned in proximity to the urinary bladder in the pelvis, but more recently an ectopic placement under the external oblique muscle of the abdomen has been described in patients who have previously undergone pelvic surgery.

Ectopic placement of the reservoir now represents the solution of choice in patients who have undergone previous extensive pelvic surgery as the classical placement in the pelvis would be associated with a significant risk of injury of the intra-abdominal organs. In the past these patients were managed with insertion of the reservoir under direct vision though a second abdominal incision. Ectopic placement of the reservoir is safe, as the device is positioned above the fascia transversalis, well away from the intra-abdominal organs, and avoids the inconvenience of performing a second abdominal incision.

Penile prosthesis implantation is usually performed under general anaesthetic and the procedure takes less than one hour. Patients are discharged the day after and usually are able to engage in penetrative sexual intercourse after six weeks.

In the hands of experienced high volume surgeons, this procedure is very safe with patients' and partners' satisfaction rates well above 95%.

Mechanical reliability of the device is also extremely high and in most patients the implant is still perfectly working after 10 years. Furthermore, if the device stops working, it can be easily replaced.

Penile shortening due to Peyronie's Disease: a solution is possible?

Peyronie's Disease is associated with the formation of anelastic scars on the tunica albuginea of the penis. As the scar does not stretch as the surrounding tunical tissue, during erections it can cause deformity and a degree of penile shortening. A degree of erectile dysfunction is also a common finding in patients with Peyronie's Disease.
Classically, patients with Peyronie's Disease and refractory erectile dysfunction are managed with penile prosthesis implantation in order to obtain the straightening and the rigidity necessary to engage in penetrative sexual intercourse.
Although successful in correcting the deformity and the erectile dysfunction, penile prosthesis implantation alone is not able to restore the length lost due to Peyronie's Disease, and this is why postoperative satisfaction rates in this subgroup of patients is not as high as in the other subgroups of implant patients, where no preoperative loss of length is present.
In order to address the loss of length, a very selective group of patients with Peyronie's Disease and severe shortening can now be offered penile length and girth restoration in combination with penile prosthesis implantation. This is a very complex procedure that should be performed only by high volume experienced implant surgeons. Once the penis is disassembled into the urethra, the neurovascular bundle and the corpora cavernosa, the length and girth are restored by incising circumferentially the tunica albuginea and filling the defect with a graft. In experienced hands, results can be very encouraging, with an average gain of 3.5 cm in length.
Complication rates following this procedure is however higher that after penile prosthesis implantation alone and should therefore be offered only to carefully selected and highly motivated patients.

Further reading:

• Rolle L, Ceruti C, Timpano M, Sedigh O, Destefanis P, Galletto E, Falcone M, Fontana D. A new, innovative, lengthening surgical procedure for Peyronie’s disease by penile prosthesis implantation with double dorsal-ventral patch graft: the “sliding technique”. J Sex Med. 2012 Sep;9(9):2389-95. doi: 10.1111/ 1743-6109.2012.02675.x. Epub 2012 Mar 16. PubMed PMID: 22429331.
• Rolle L, Falcone M, Ceruti C, Timpano M, Sedigh O, Ralph DJ, Kuehhas F, Oderda M, Preto M, Sibona M, Gillo A, Garaffa G, Gontero P, Frea B. A prospective multicentric international study on the surgical outcomes and patients’ satisfaction rates of the ‘sliding’ technique for end-stage Peyronie’s disease with severe shortening of the penis and erectile dysfunction. BJU Int. 2016 May;117(5):814-20. doi: 10.1111/bju.13371. Epub 2015 Dec 21. PubMed PMID 26688436.

Surgery for Peyronie's Disease. Which is the perfect procedure?

Surgery still represents the best solution in patients with stable Peyronie's Disease. The aim of surgery in Peyronie's Disease is to guarantee a penis straight and rigid enough to allow the patient to resume sexual activity with confidence. 

At present, more than 50 different types of procedures have been described in the literature and the question "is one technique better than another?" is perfectly legitimate. However, unfortunately the answer is "no".

The reason why there are many type of procedures is not only that different techniques are indicated according to the type of the deformity, the degree of penile shortening and the quality of the erections, but also that a perfect type of procedure still does not exist, as none of the procedures can bring back the exact pre Peyronie's Disease size and shape of the penis.

Surgical procedures available at present can be subdivided in 3 main cathegories: 1) Simple plication procedures; 2) Complex corporoplasty with plaque incision and grafting; and 3) Penile prosthesis implantation with additional straightening procedures. Each one of these categoris has its own indications, advantages and disadvantages. 

Penile prosthesis implantation is indicated in patients with refractory erectile dysfunction or with a degree of erectile dysfunction and complex deformity and/or severe penile shortening. This procedure guarantees adequate correction of the deformity and the rigidity necessary to engage in penetrative sexual intercourse.

Simple corporoplasties (such as Nesbit, Yahia and Tunica Albuginea Plication or TAP) are indicated if the curvature is less than 60 degrees, if penile shortening is not excessive and if there is no waist deformity. These procedures are not associated with postoperative worsening of the quality of the erections and are reasonalbly simple to perform. These procedure induce straightening by shortening the longer side of the shaft (the one ont affected by Peyronie's Disease). It is estimated that a shortening of 1 cm is necessary to correct 20 degrees of curvature and therefore these procedures are not indicated for curvatures of more that 60 degrees, as this would require a shortening of 3 cm at least to produce adequate straightening.

Complex corporoplasties involving plaque incision and grafting (such as the Lue procedure) are nieche procedures due to their complexity and therefore need to be performed only by experienced large volume surgeons in order to achieve adequate results. 

Patients with good quality erections and complex deformity, waist, severe shortening and curvatures of more than 60 degrees are the only candidates for this type of procedure. As plaque incision and grafing can worsen the quality of the erection in around 15% of cases, patients with a preexistent degree of erectile dysfunction are not candidates for this procedure, as they are likely to become fully impotent afterwards, and should be offered penile prosthesis implantation instead.

Finally, when discussing Peyronie's Disease surgery, it is very important to adequately counsel the patient and manage patient's expectation. Once the patient is fully counselled about the risks and benefits of each procedure, he can make an informed decision of the procedure he wants to undergo. In order to achieve higher patient's satisfaction levels, patient's expectations need to be realistic. In particular, the patient needs to accept that surgery will not remove Peyronie's Disease or restore fully the shape and size of the penis before the onset of the disease, but it will render the penis straight and rigid enough to engage in penetrative sexual intercourse with confidence.

State of the art in female to male transsexual surgery

Female to male sex reassignment surgery remains a very challenging and long process. Patients should be followed by a multidisciplinary team of dedicated experts including psychiatrists, endocrinologists, plastic surgeons, gynaecologists and reconstructive urologists in order to achieve the best possible outcome from the transformation. 

At present, the radial artery phalloplasty represents the best choice for penile construction in these patients. This technique allows the creation of a very realistic phallus with tactile and erogenous sensation and with an incorporated neourethra to allow patients to void from the tip of the phallus while standing. After the implantation of an erectile device patients are also able to engage in penetrative sexual activity with confidence. 

This procedure, when performed by large volume surgeons, is very reliable and safe. Currently Mr Garaffa, who is a Consultant Uro-Andrologist at the University College London Hospitals is the reconstructive surgeon who currently performs the largest number of total penile reconstructions in the world and this has been the topic of the uT@lks at the 2016 SIU Congress in Buenos Aires, Argentina.

The lecture can be found on this link: https://vts.inxpo.com/scripts/Server.nxp?LASCmd=AI:1;S:17;F:QP!14100&EventKey=198199&EventAttendeeKey=17770578&ShowKey=34265&EventScreenCaptureMode=NULL&RandomValue=1477949880058

More information can be found on this link: http://siu-urology.org/newsletter/2016/mailblast-332.htm

Erectile dysfunction can help the physician to identify early cardiovascular risk factor and prevent cardiac events

This interesting review confirms how erectile dysfunction and major cardiovascular events such as heart attacks and strokes are caused by the same underlying problem, which is diffuse cardiovascular disease.

Sedentary lifestyle, obesity, high cholesterol levels, diabetes, hypertension and cigarette smoke are well known cardiovascular risk factors, which in the long term can cause obstruction of the arteries and vascular disease. 

When an artery gets progressively blocked the blood flow progressively reduces. If this happens in the arteries of the penis, the patient will notice a progressive worsening of the quality of the erections, while if the blockage occurs in the arteries of the heart or of the brain, the patient will experience respectively a heart attack or a stroke.

Since the vessels who are smaller are the one that will show the sign of a blockage first and since the vessels in the penis are smaller than the ones in the heart and in the brain, patients will develop signs of erectile dysfunction a few years before experiencing heart attacks or strokes.

It is therefore very important that patients seek immediate medical attention when they develop the first signs of erectile dysfunction. 

A thorough medical evaluation can not only help the patient to restore an adequate erectile function but also identify and treat potential cardiovascular risk factors that may cause fatal events a few years later. 

This will prevent the patient from suffering from a cardiovascular event and guarantee him a much longer life expectancy.

This article should therefore represent a strong invitation to patients not to be ashamed of their erectile dysfunction and to seek medical attention not only because effective treatments are now available in almost all cases but also to prevent the development of serious cardiovascular events in the near future.

For further reading please click on the following link

http://eurheartj.oxfordjournals.org/content/ehj/34/27/2034.full.pdf

total penile reconstruction following traumatic amputation of the penis

An innovative article describing total penile reconstruction with the use of the forearm free flap in patients who have previously experienced traumatic amputation of the penis has been recently published on "The Journal of Sexual Medicine", the most prestigious international journal in andrology.

This represents the largest series of patients who have undergone total penile reconstruction with the use of a forearm free flap ever described in the literature. All the procedures have been carried out at the University College London Hospital by an equipe led by Mr Garaffa and Mr Ralph, who are the world leading experts in total penile reconstruction. 

After a very complex surgical procedure, reconstruction of a neophallus has been possible in all patients. This operation has allowed the creation of a cosmetically acceptable phallus with both cutaneous and erogenous sensation. Patients were therefore able to resume a normal sexual and urinary function.

These series confirms the encouraging results of the forearm free flap phalloplasty previously described by Mr Garaffa and Mr Ralph in patients who have undergone penile amputation for penile cancer, in these with micropenis and in female to male transsexuals.

The forearm free flap phalloplasty represents the best option in patients who require total penile (re)construction as it guarantees superior results in terms of sensation, function and cosmetic appearance. 

So we can now say that penile reconstruction is now possible and that results an be excellent..