Tuesday, 29 November 2016

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. 

Monday, 7 November 2016

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.

Thursday, 3 November 2016

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.