Thursday, August 26, 2010

Pharmacotherapy in Male Reproductive system disorders

MEDICAL MANAGEMENT OVERVIEW IN ANDROLOGY:

ERECTILE DYSFUNCTION:

Pharmacotherapy of ED could intervene in the CNS: ALPHA 2 ADRENERGIC BLO0CKERS (YOHIMBINE,PHENTOLAMINE)and dopaminergic antagonist (APOMORPHINE ) or peripherally agents that enhance , elevate or directly stimulates the synthesis of secondary messenger molecules such as c AMP or c GMP and direct activators of adenylate cyclase for ex: Phosphodiesterase inhibitors :non selective –papaverine, Type 5 –sildenafil citrate,vardenafil,Tadalafil,Type 3 Milirinine and Type 4 roliparm
Drugs for treating ED can be taken orally, injected directly into the penis, or inserted into the urethra at the tip of the penis. In March 1998, the Food and Drug Administration (FDA) approved Viagra, the first pill to treat ED. Since that time, vardenafil hydrochloride (Levitra) and tadalafil (Cialis) have also been approved. Additional oral medicines are being tested for safety and effectiveness. Viagra, Levitra, and Cialis all belong to a class of drugs called phosphodiesterase (PDE) inhibitors. Taken an hour before sexual activity, these drugs work by enhancing the effects of nitric oxide, a chemical that relaxes smooth muscles in the penis during sexual stimulation and allows increased blood flow.While oral medicines improve the response to sexual stimulation, they do not trigger an automatic erection. The recommended dose for Viagra is 50 mg, and the physician may adjust this dose to 100 mg or 25 mg, depending on the patient. The recommended dose for tadalafil(Megalis,Forzest) is 10 mg, and the physician may adjust this dose to 20 mg if 10 mg is insufficient. A lower dose of 5 mg is available for patients who take other medicines or have conditions that may decrease the body's ability to use the drug.
None of these PDE inhibitors should be used more than once a day. Men who take nitrate-based drugs such as nitroglycerin for heart problems should not use either drug because the combination can cause a sudden drop in blood pressure. Also patients have severe cardiac diseases like recent Myocardial Infarction, reduced stress tolerance should avoid PDE-5 inhibitors.

sildenafil
tadalafil
verdenafil
Maximum plasma concentration
30-120 (median 60)
30-360 (median 120)
30-120 (median 60)
Half life hours
4
17.5
4-5
Duration of action
up to 4-12
up to 36
Up to 4-12
Food restriction
may take longer to work with meals
can be taken with or with out food
can be taken with or without fatty foods
INTRA CAVERNOSAL INJECTION OF VASO ACTIVE DRUGS (ICIVAD)
Many men achieve stronger erections by injecting drugs into the penis, causing it to become engorged with blood. Drugs such as papaverine hydrochloride(15- 60 mg), phentolamine, and alprostadil (marketed as Caverject) widen blood vessels. These drugs may create unwanted side effects, however, including pain (36%) persistent erection (4%) and scarring. It gives a success rate of 70-90 % but these injections have a drop-out rate of 25-60% because of mainly pain or sometimes development of corporal fibrosis.
Methodology of giving papavarine/bimix:
Start with 29-30 G Insulin syringe for the injection therapy.

Papavarine:It can be started with 15 and given till 60 mg. Inject in any corpus.
Bimix: Add chlorpromazine ( 4 ml papavarine to 0.1 ml chlorpromazine combination) start with 0.1 to 0.2 ml and then gradually increased .Again the injection can be given in any one of the corpus
Drug therapy for Peyronie’s disease:
Medical Treatments
Various medications like Vit E 400 mgs three times a day for 3 months, Cochicine 0.5 mg 2 bd for 3 months or Tamoxifen 20 mg BD for 3 months.The placebo controlled trioals have not shown efficacy of the medications but colchicines there are no placebo studies. It seems to be effective.

Researchers have also tried injecting chemical agents such as verapamil, collagenase, steroids, and interferon alpha-2b directly into the plaques. Verapamil and interferon alpha-2b seem to diminish curvature of the penis. The other injectable agent, collagenase, is undergoing clinical trial and results are not yet available. Steroids like triamcilone have caused loss and atrophy of the local tissues and weakening of the tunica. The surgical planes also become difficult after steroid injection.
The intralesional injections are given with 24 G needle making multiple passes through the plaque.There is a possibility that the multiple passes make the plaque weak by mechanical disruption.
Intralesional Therapy:
1) Intralesional Verapamil
Dose 10 mg verapamil/4ml+6mlsaline total 10 ml ;2 weekly for 12 injections
Promising but un proven
2)Intralesional interferon -alpha-2b
Dose: 1millon units 2 weekly for 12 injections
Placebo trial-ongoing
Possibly useful
3)Intralesional Steroids
Dose 40 mg triamcinolone /ml, dilute as per size 6 weeks total 6 injections
Steroids may weaken tunica loss of surgical planes due to trauma

IDIOPATHIC OLIGOSPERMIA :MANAGEMENT


Despite advances in diagnostic modalities up to 25% patients exhibits unexplained infertility. A variety of medical therapies have been suggested to treat this group. However none of these have sown effective to be repeated controlled trials. A meta-analysis of all controlled studies for idiopathic male infertility has failed to reveal significant efficacy of currently available treatment .In the hope that they may be effective in a selective group of people a minimum of 3-6 months trial should be given to include at least one cycle of spermatogenesis
The empirical therapy includes the following drugs:
1) Hormonal agents (direct or rebound effect):The testosterone undecanoate 80-160mg/d, Testosterone enanthate or propionate inj 2-3 weekly Side effects: Azoospermia ,gynecomastia, cholestasis and hepatic dysfunction

2) Antiestrogens : Clomiphene citrate 25-50 mg daily, Tamoxifen 10-30 mg daily, Side –effects: nausea, weight gain loss of libido, headache ,gynecomastia, dermatitis.

3)Antioxidants: The oligospermia is many a times attributed to Reactive Oxygen Species.Various agents are prescribed to nullify the effects of Reactive Oxygen Species like glutathione,Lycopene-4mg/d, Vitamin E 400-800mg/d,N-Acetyl Cysteine 1000 mg/day.
4)Sperm vitalizers : Cellular Energisers like L-Arginine,Zinc, Selenium, proanthrocyanidin , Carnitine 1-2 mg/d CoQ10 10-400mg/d,Pentoxiphylene

If this is unsuccessful ,Assisted Reproductive Technique (ART) is employed or a combined approach may be started simultaneously in older couples.

Specific medical therapy in oligospermia:
Chronic fungal dermatitis
Anti fungal topical cream For ex.Candid B ointment locally

Chronic filarial epididymo-orchitis
Anti filarial &anti-inflammatory drugs-Hetrazan 100 mg three times a day for 3 weeks
Seminal Infections:-
Whether infection causes infertility is still controversial. There are several conflicting reports of benefit of treatment. The semen analysis showing plenty of pus cells should be discussed with the seminologist so as to remove any confusion of round cells with immature spermatogonia. Semen culture should be done in such cases.The common seminal organisms are:Streptococcus fecalis,E coli,Coagulase +ve staph (albus) or Occasionally Klebsilla , proteus,pseudomonas. Ciprofloxacin/doxycyclins can be administered as per the semen culture sensitivity report for a period of 4-6 weeks. As a rule, both sexual partners should be treated at the same time.In the mean time condom intercourse can be performed. At the end of the treatment it should be confirmed that infection is eradicated as there is tendency for chronicity

Antisperm antibodies: The direct test should be done for ASA and if present should be treated on priority with Intra-Uterine Insemination.The other modality of treatment is giving prednisolone 5 mg three times a day for 3-12 months.

Management of hypogonadotrophic hypogonadism:
Management delayed puberty: No initiation of puberty by age 13 in girls and 14 in boys
Delayed puberty Management
Injection testosterone esters are given in the strength of 50-100mg per month for 3-6 months.This This dose will advance puberty without impairing height potential.The spontaneous onset of puberty should be awaited for 3-6 months if there is no initiation formal testosterone replacement therapy should be given.
Management of pre pubertal Hypogonadotropic Hypogonadism

The treatment should be based on androgenising the patient. So it is usually done by giving testosterone or HCG.

Testosterone Replacement Therapy for Androgenisation:
Inj Sustanon deep IM in the following protocol:to start with 100 mg deep intramuscular every month for 3 months.This dosage is progressively increased to 250 mg once a month followed by 250 three weekly for long term treatment. When fertility is desired LH and FSH support is usually given with proper counseling as the cost of the therapy may be 2-3 lakhs with 50 % chance of conception.
The underlying principle is to achieve initial testicular growth with LH (LH is given as HCG. 5000 u one injection per week , 2000 u two to three injections per week.HCG dose monitoring is done by assaying testosterone on Day 3(for response) and Day 7(for sustenance).Testicular volume is monitored along with the signs of androgenisation. When testicular volume become 18 ml and ejaculation starts then FSH are added to complete spermatogenesis.FSH is started in the form of HMG
Dose options:37.5 units thrice-a-week/75 u thrice-a-week/150 u thrice-a-week
This is continued till pregnancies occur. The count may increase from azoospermia to 5-10 millions/ml so Assisted Reproductive Technology may be needed.Testosterone is restarted after pregnancy is over.

Drugs Therapy in Premature Ejaculation
Local anaesthesia: Topical anesthetics/gel are sometimes given with the idea of desensitizing the glans and delaying the orgasm. Lignocaine cream can be given for application for 20 minutes before the sexual act.
Medications:
Normally Selective Serotonin Uptake Inhibitors are used for such patients along with psychotherapy. The mechanism of action of SSRIs is linked to their inhibition of neuronal uptake of serotonin in the CNS. They prolong the sexual climax causing relief from early unwanted ejaculation.
These SSRI (Sertraline,Paroxetene.Fluoxitine)may take until at least 3 weeks following initiation of treatment to cause improvement in sexual latency.
Dose of the medications:
Clomipramine (clonil) 10-25 mg
Paroxetine(parotin) 10-20 mg
Sertaline (sertima) 25-100 mg
Fluoxetine(prodep) 20-40 mg
These drugs may cause side effects like yawning,anejaculation,decreased libido,perspiration and increased fatigue.

It has been seen that many patients with PE have undelying erectile dysfunction also so adding PDE-5 inhibitors like Viagra(sildenafil),Tadalafil works well.
Dapoxetine is an SSRI developed specifically for the treatment of premature ejaculation. Dapoxetine may be effective at first dose (ie, on-demand) for premature ejaculation when given 1-3 hours prior to sexual intercourse.
The optimal medical treatment for premature ejaculation has not been established but single dosing prior to sexual relations can work for many males.While raised blood levels through daily use of the medication may be unnecessary resulting in many CNS side effects. Obviously, if single dosing is successful, therapy is simpler and is associated with fewer adverse effects. Therefore, this may be the preferred initial therapy.
Dapoxitine right now although is manufactured in India ;is not available in market.But it soon expected after Food Drug Administration approves it.


Dosage of the testosterone and diagnostic evaluation:
The level of total testosterone below < 200-250 ng/dl of total testosterone /,8 nmol/L total testosterone or <3.8nmol/L bioavailable testosterone/<0.255 nmol/L free testosterone is indicative of low testosterone level. The actual threshold will vary as per previous levels life styles and habits.
Various types of testosterone replacement:

Testosterone therapy injectable
· Testosterone enanthate (testoviron depot)200-400 mg/4 weekly deep IM
· Mixed testosterone esters (sustanon) 250 mg/3 weekly deep IM
Highly effective inexpensive but causes Wide variations in level so the effect can be erratic like mood variations in the patient.

Oral
Testosterone undecoate (andriol)160mg/day. It should be taken
after full meals.

Gel
Available in 5g to 10g sachets. It is applied to shoulders and chest. After application 15-20 minutes are allowed to dry. The patient should avoid bath or swimming for 6 hours there after. The gel causes physiological levels to be attained without variations. The side effects are skin rash in some.

Spray
4-6 sprays every day. It is applied to shoulders and chest. After application 5 minutes should be given for application. The patient should avoid bath or swimming for 6 hours thereafter as in gel. The gel causes physiological levels to be attained without variations.

Adjusting dose schedule:
Check testosterone level before using the 30 week dose
Testosterone level recommended dosing interval
10-15 nmll/L continue at 12 weekly intervals
<10nmol/L continue at 10 weekly intervals
<15 nmol/L continue at 14 weekly intervals

a)Monitoring during testosterone therapy

b) Monitor for response: Primarily symptomatic, there will be increase in libido, energy and feeling generalized well being. The erectile dysfunction will start resolving. Generalised muscle strength as witnessed by handgrip and cognition will also improve.Bone density will also increase.

c) Monitor for complications: Hyperviscosity syndrome, increase in RBC mass,so complete blood count and hematocrit should be monitored. If hematocrits increase more than 55% then therapy should be stopped. There is a risk of exaggeration of pre-existing carcinoma prostate. The therapy as such doesnot increases the risk of prostatic malignancy. The risk of sleep apnea syndrome is increased as the central response to CO2.Liver Function tests also may deteriorate so need to monitor LFT,PSA,Hematocit.

Peyronies disease

Peyronie’s Disease

Peyronie’s disease is characterized by a plaque, or hard lump, that forms within the penis. The plaque, a flat plate of scar tissue, develops in the tunica albuginea part of the penis, which is a covering of the erectile tissues. This condition was described by Fallopius in 1561 and popularized by Gigot de la peyronie in 1743.
The average age of onset of the disease is 53 years and its prevalence is 3.2% in sexually active men.

Presentation:
Cases of Peyronie’s disease range from mild to severe. Symptoms may develop slowly or appear overnight. In severe cases, the hardened plaque reduces flexibility, causing pain and forcing the penis to bend or arc during erection. In many cases, the pain decreases over time, but the chordee may remain a problem, making sexual intercourse difficult. The sexual problems that result can disrupt a couple’s physical and emotional relationship and can lower a man’s self-esteem. Natural history of the disease goes through an active phase of painful erection and changing plaque configuration followed by a secondary phase of painless deformity and progressive calcification. The disease is progressive in 30-40% cases and stable in 40-50% but the spontaneous resolution is rare.



About 30 percent of men with Peyronie’s disease develop other fibrotic disorders as Dupuytren’s contracture of the hand. Familial association,diabetes and urethral instrumentation are other causes for Peyronies disease.

Pathophysiology:

The trauma is believed to be central reason behind the Peyronies disease.The trauma to the penis causes buckling of the area of the attachment of the central septum with the tunica albugenia causing rupture of the blood vessesls. The hematoma is accompanied by the accumulation of the inflammatory mediators. The Peyronies disease goes through three stages:
Step 1: Inflammatory exudates between cavernosa and albuginea consisting of Lymphocytes macrophages, plasma cells which secrete Active cytokines TGF ß1 .The TGF ß1 increases collagen synthesis, proteoglycans, fibronectin

Step 2: Fibrous infiltration of the sub tunical layer
Step 3: Extensive localized fibrosis and ossification
The plaque causes chordee and venous leak which causes erectile dysfunction. iNOS deficiency is also supposed to be cause behind erectile dysfunction.



Diagnosis:
Doctors can usually diagnose Peyronie’s disease based on a physical examination. The plaque can be felt when the penis is limp. The erection may be induced by injecting intracavernosal papavarine or bimix and an Doppler ultrasound scan of the penis to pinpoint the location and calcification of the plaque and concomitant venous leak may be done. A photograph may be taken to document the angle of chordee prior to surgical treatment.

MEDICATIONS:
The goal of therapy :
1) To restore and maintain the ability to have intercourse.
2) To decrease the pain
3) To allay the fears in mind of the patient and re-educate him about the disease.
4) To restore cosmetic appearance
Experts usually recommend surgery only in long-term cases in which the disease is stabilized and the deformity prevents intercourse.
Medical Treatments
Various medications like Vit E 400 mgs three times a day for 3 months, Cochicine 0.5 mg 2 bd for 3 months or Tamoxifen 20 mg BD for 3 months.The placebo controlled trioals have not shown efficacy of the medications but colchicines there are no placebo studies. It seems to be effective.

Researchers have also tried injecting chemical agents such as verapamil, collagenase, steroids, and interferon alpha-2b directly into the plaques. Verapamil and interferon alpha-2b seem to diminish curvature of the penis. The other injectable agent, collagenase, is undergoing clinical trial and results are not yet available. Steroids like triamcilone have caused loss and atrophy of the local tissues and weakening of the tunica. The surgical planes also become difficult after steroid injection.
The intralesional injections are given with 24 G needle making multiple passes through the plaque.There is a possibility that the multiple passes make the plaque weak by mechanical disruption.
Surgery
Three surgical procedures for Peyronie’s disease is done for curvature more than 45 degrees in angle making sexual intercourse difficult.Various procedures have been followed like placation(problem of further shortening penis),incision or excision and grafting(tunica vaginalis or saphenous vein graft) or implantation of penile prosthesis.
If the implant alone does not straighten the penis, implantation is combined with one of the other two surgical procedures.

ROLE OF ROBOTIC SURGERY IN ANDROLOGY

Robots To Cure Male Infertility
Recent studies have shown that Male Infertility is on the Rise due to decrease in average sperm count, as we are step into the 21 st century.
This can be attributed to genes, infections, life style changes, smoking, drug abuse, mental stress due to pressures at work, obesity, hypertension, and environmental and pesticide pollutants. This means more and more males will become infertile and will have to resort to medical, surgical and Assisted Reproductive Treatment to help their partners conceive

Over the past 30 years, the treatment of infertility has seen the development of revolutionary new assisted reproduction techniques like In-Vitro Fertilisation (IVF) and Intra-Cytoplasmic Sperm Injection (ICSCI)
These highly complex techniques are used with increasing frequency in the treatment of couples around the globe.
More than 1 million babies worldwide have been conceived by these new techniques giving immense satisfaction to infertile couples.
Both IVF and ICSCI involve conception in a Test Tube and hence bypass natural conception. There is therefore a risk of undesirable genetic traits being passed on to next generation.
IVF and ICSI are also advised in Males who have a poor sperm count and in whom medicine or surgery cannot help to improve the sperm count.
Recent technological advances have enabled the use of Robotics and Micro Surgical assisted techniques to improve sperm counts. This helps conception in a more natural form and avoids the use of IVF and ICSCI when the Male is responsible for the lack of conception in an infertile couple
The infertile males either have a low sperm count ( due to inadequate sperm production also known as Oligospermia) or have no sperms in the semen (Azoospermia) .

When Azoospermia is due to a block in the tubes (Epididymis, Vas Deferens, Ejaculatory Duct) transporting the sperm it can be cured surgically by advanced techniques called VasoVasostomy, VasoEpididymoAnastomosis or Seminovesiculoscopy. These surgeries are very delicate and time consuming as they involve operating on structures smaller than the heart vessels.

With advances in MicroSurgery and Robot Assisted MicroSurgery the chance of sperm (re) appearance rate can be as high as 80%.. Without the use of these techniques the chances of sperm (re)appearance is as low as 5 %.
Robotic vasectomy reversal
The advantage of microsurgical reconstruction is that once successful, natural conception is possible time and again without the mental agony of going through multiple IVF or ICSCI cycles apart from the huge recurring costs.
Multiple data from leading centers all over the world have proven the cost effectiveness of Microsurgical and Robotic Microsurgical reconstruction over the routine sperm retrieval for IVF and ICSI.


In oligospermia (Low Sperm Count) due to poor sperm production either due the enlarged veins surrounding the testes
( Varicocele), microsurgery allows a success rate of almost 60% (pregnancy rate).

In cases where the low sperm count is due to disease in the testes Microsurgical Sperm Retrieval (Micro-dissection TESE) techniques can find sperm in Testis.
In conclusion recent advances in Robotics and MicroSurgical Techniques have given new hope to an infertile male to conceive in a natural way.

Empty scrotum:management strategy

Empty Scrotum


Cryptorchidism is a common disorder in pediatric urology. It has been observed to occur in 3% of term infants and 30% of premature infants; however, 75% and 90% of these undescended testes, respectively, will have spontaneously descended by age 1 year, leaving a true incidence of close to 1% (0.8%) of the male population. Ten percent of cases are bilateral, 3% of which will have one or both testes absent. The etiology is unclear, and although many genetically inherited diseases have a high association with cryptorchidism, most cases of the undescended testis are isolated with no evidence of a genetic component.

SIGNIFICANCE
· A 33-fold increased risk of developing a testicular malignancy has been noted with undescended testes.
· Ten percent of testicular cancers arise in an undescended testis, 60% of which will be seminomas.
· The intraabdominal testis is four times more likely to undergo malignant degeneration than is an inguinal testis.
· Fertility is impaired. Only 30% of patients with bilateral cryptorchidism even after the surgery will be fertile. Spermatogenic damage appears to increase with higher position and longer periods of extrascrotal habitation.
· A high incidence of associated inguinal hernias (30%) occurs because of the patent processus vaginalis.
· An increased susceptibility to torsion exists, especially in postpubertal period.
· An increased susceptibity for trauma.

CLASSIFICATION
· Intraabdominal (10%)—testis is located proximal to the internal inguinal ring within the abdominal cavity.
· Inguinal canal—testis is located between internal and external intuinal rings.
· Ectopic—testis is located distal to the internal ring but outside its normal path of descent. Most are found in the superficial inguinal pouch or in perineum, femoral canal, suprapublic area, and, rarely, in the contralateral scrotal compartment.
· Absent testis (4%)—20% of nonpalpable testes are absent.
· Retractile testis—testis is not truly undescended. Its extrascrotal location is secondary to hyperactive contraction of the cremasteric muscle. It is commonly found in the prescrotal or low inguinal area and with gentle manipulation can be placed in the scrotum without tension.

DIAGNOSIS
Carefully palpate both scrotal compartments, the inguinal canals, perineum, suprapubic area, and femoral canal. A palpable testis will be inguinal, ectopic, or retractile. If the testis can be easily placed within the scrotum without tension, it is retractile. Note that the cremasteric reflex is most active between ages 2 and 7 years, making this diagnosis difficult. A nonretractile palpable testis is either inguinal or ectopic.
A nonpalpable testis is either intraabdominal, ectopic, inguinal, or absent. If both testes are impalpable, then measure serum testosterone response to human chorionic gonadotropin (HCG) stimulation (HCG 2,000 IU daily 3days) and basal follicle-stimulating (FSH) and luteinizing hormone (LH) levels. A negative testosterone response to HCG and elevated basal FSH and LH levels are reliable evidence of anorchism (bilateral testicular absence). Bilateral or unilateral non palpable nondescensus can be further investigated by ultrasound, computed tomography, laparoscopy, and surgical exploration. Most testes will be found at surgery close to the internal inguinal ring.

TREATMENT

Why Treat Undescended Testis?
· The surgery will not reduce the malignancy occurrence chance but certainly it will make the testis more easily palpable for the patient and the surgeon.
· To repair inguinal hernias(30% patients have chance of co-existing hernia)
· To decrease risk of torsion
Therapy should be undertaken between ages 6 and 18 months. This will allow adequate time for spontaneous descent to occur and should minimize the potential complications of infertility and malignant degeneration. Retractile testes need no further therapy; however, periodic reexamination to confirm the diagnosis would be prudent. The truly undescended testes can be treated with either hormonal or surgical therapy or both.

Hormonal Therapy

HCG has been used to bring down the testis in up to 70% patients, respectively. Hormonal therapy is contraindicated with ectopic testes, in the setting of a hernia, and after prior orchiopexy or herniorrhaphy (because of the scarring).

Surgical Therapy

Several different procedure for orchiopexy are effective, all based on the principles of adequate mobilization and fixation and repair of the associated hernia in one stage or in two stages.
Occasionally, greater mobilization of the proximal spermatic cord structures does not provide adequate length to allow for tension-free placement of the testis within the scrotum. Greater cord length can be obtained by mobilizing the spermatic vessels medially. The spermatic vessels are usually the limiting factor in these circumstances. The Prentiss maneuver was described in 1960 and is occasionally helpful in adding length to the spermatic vessels by positioning the spermatic vessels medially and thereby choosing the hypotenuse of the triangle, or the most direct course to the scrotum, created by the natural course of the vessels laterally through the internal ring. It is performed by incising the floor of the inguinal canal through the external ring and dividing the inferior epigastric vessels. The internal ring and transversalis fascia are then closed lateral to the cord.
Ligation of the testicular vessels occasionally becomes a necessary consideration, especially in the management of a high inguinal or intra-abdominal testis. The technique described by Fowler and Stephens was originally a one-stage procedure, but it may also be performed in two stages. If a one-stage repair is to be performed, it is critical early in the dissection that a wide pedicle of peritoneum be preserved with the vas deferens to maintain collateral blood flow.
Orchiectomy should be performed if the testis is atrophic and cannot be brought to the scrotum.

Wednesday, August 25, 2010

Surgery for Erectile Dysfunction


Surgery
Surgery usually has one of three goals:

to implant a device that can cause the penis to become erect (Penile Implant surgery)
to reconstruct arteries to increase flow of blood to the penis (Penile revascularization surgery for patient with focal arterial stenosis-post-trauma)
to block off veins that allow blood to leak from the penile tissues (penile venous leak-particularly detected on Doppler showing persistence end-diastolic velocity more than 5 cm/sec)
Implanted devices, known as prostheses, can restore erection in many men with ED. The patient who donot respond to intracavernosal injection of vasodilator agents or Vacuum Erection Device. Neophallus reconstructed patient are also candidates for penile implant surgery. The contra-indications for the penile implant are uncontrolled diabetes,spinal cord injury patients, patients with severe psychiatric imbalance, neurogenic bladder and very short penis. The implant gives erection with causing some decrease in length so this thing has to be emphasized to the patient before the surgery.
Types of penile prosthesis are:
Non-inflatable(Malleable,hinged prosthesis)- less costly but gives constant erection and needs special clothing for concealment of the erection.
And
Inflatable(2 piece and 3 piece variety):Expensive,surgery is technically demanding but gives near to normal erection.

Choice of three piece implants

700CX: Diameter 12 to 18 mm length constant
700 ultrex: Girth 12 to 18 mm, length increases.So to a patient concerned about the length of the penis post implant this is a good choice.
700 with inhibizone coating

Description of inflatable implant:
Inflatable implants consist of paired cylinders, which are surgically inserted inside the penis and can be expanded using pressurized fluid Tubes connect the cylinders to a fluid reservoir and a pump, which are also surgically implanted. The patient inflates the cylinders by pressing on the small pump, located under the skin in the scrotum. Inflatable implants can expand the length and width of the penis. They also leave the penis in a more natural state when not inflated.
Advantages with the penile impants are:
o Good rigidity
o Freedom from medications
o Outpatient/24HR surgery
o Resume sexual activity 4-6 weeks
o No loss of ability to ejaculate or achieve orgasm

Surgery to repair arteries can reduce ED caused by obstructions that block the flow of blood. The best candidates for such surgery are young men with discrete blockage of an artery because of an injury to perineum or fracture of the pelvis.Surgery to veins that allow blood to leave the penis usually involves an opposite procedure-intentional blockage. Blocking off veins (ligation) can reduce the leakage of blood that diminishes the rigidity of the penis during erection. However the results are not long lasting so the venous ligation surgery have diminished


PHOTOGRAPHS OF PENILE IMPLANT SURGERY BEING DONE


COMPLICATIONS OF PENILE IMPLANT:
Infection (5-14%)
Infection in the periprosthetic space usually does not cause significant illness; however, to eradicate the infection, removal of all components of the prosthesis is almost always required.
Infections occurring after penile prosthesis implantation are either early (in the first few weeks following implantation) or late (6 months to 1 or 2 years after implantation). The former are often associated with gram-negative bacteria, whereas the later are usually associated with gram-positive bacteria such as Staphylococcus epidermidis. Early infections are usually acquired during the surgery. 56% of cases occur within 6 months, 36% occu within 7-12 months and 2.3% after 5 months.
Pre-operatively cephalosporins and aminoglycosides should be administered and post-operatively quinolones should be given.
Early infections are likely to be evident by swelling, erythema, tenderness, possible purulent drainage, and occasionally fever. Late infections may be manifested only by persistent or recurrent long-term pain. With long-term infections the scrotal skin may be adherent to the pump.
Treatment of a prosthetic infection with appropriate antibiotics usually results in clinical improvement; however, antibiotic treatment rarely permanently eradicates this type of infection. This is thought to be due to harboring of microorganisms within a biofilm that is adherent to the device. For this reason, when a prosthetic infection is present, all components of the prosthesis should be removed.The corporal spaces should be lavaged with antibiotic solutions. Vancomycin and Gentamycin should be used for lavage.
After the infection has come into control usually in the interim period the Vacuum Erection Device should be encouraged.The advantage being the VED will cause stretching the corpora and to certain extent increase the length and the girth of the penis and cause easier dilatation during the second surgery.
When all incisions have healed and postoperative edema has resolved (usually 2 to 3 months after device removal), reimplantation is advised because early fibrosis is easier to dilate and the scar contraction that leads to shortening has not yet occurred.
New Inhibizone Implants have come with antibiotics-Rifampicin and Minocyclin.
Perforation and Erosion
Perforation is an event that occurs intraoperatively; whereas erosion is an event that occurs or is recognized only postoperatively. When the surgeon is dilating the proximal corpora (crura), a sudden give of the dilator suggests that the crus has been perforated on its medial aspect near its attachment to the pelvic bone. The dilator, almost always a smaller size, travels out into the soft tissues of the perineum. Mulcahy suggested the “wind sock” correction for this, but it is rarely necessary if the perforation is recognized and larger diameter dilators are used to dilate the correct track. When the proximal portion of the cylinder is inserted, it stays within the crus and the small area of perforation heals over it.
With distal dilation, crossover to the opposite side may occur or the urethra may be perforated. If urethral perforation occurs, the implant procedure should be abandoned and a urethral catheter should be left in for 7 to 10 days. Prosthesis reimplantation may be done at a later date. To avoid urethral perforation, the surgeon should keep the tip of the dilator under the dorsolateral surface of the corpus cavernosum. This maneuver also helps to prevent crossover to the opposite side. After the first cylinder is implanted, the surgeon should resound the other side both proximally and distally to see whether crossover in either direction has occurred.
Erosion of the distal end of the prosthesis may occur into the urethra, in which case it is visible through the meatus. This occurs more commonly after semirigid rod implantation, presumably because of constant internal pressure from the rod device. It also occurs more commonly in men with spinal cord injury because of their lack of sensation. In the case of urethral erosion, a urethral catheter is placed for 10 days to allow urethral healing. Many patients are able to have adequate coitus with only one rod in place; hence, a procedure to reimplant the second rod is usually not necessary.
Poor Glans Support
Poor support of the glans penis by cylinder or rod tips leads to a drooping appearance of the glans, which is commonly referred to as the SST deformity after the supersonic transport (Concorde) nose appearance on takeoff and landing. This deformity may result from inadequate distal dilation, too short cylinders, or, in the case of minor deformity, variations in anatomy.
Correction of this deformity can be done in one of two ways. The definitive correction involves removing both cylinders, perforating the distal capsule with Metzenbaum scissors, redilating the distal corpora, resizing, and then inserting longer cylinders or the same cylinders with longer rear tip extenders. Alternatively, dorsal plication of the glans back onto the shaft of the penis can be performed. The latter procedure is preferable when there are minor but otherwise bothersome degrees of SST deformity.

Pump Complications
The technique for pump implantation discussed previously helps to avoid upward pump migration, which tends to take place during healing because of the action of the cremasteric muscles. If upward pump migration occurs, the pump may impinge on the base of the penis, making use of the pump difficult and also interfering with intromission. Revision is sometimes necessary, at which time the pump is relocated to its correct position.
The pump may also be difficult to use if a hematoma or seroma forms around it. These may reabsorb with time; if they do not, pump revision may be necessary.
Autoinflation
Autoinflation occurs when the inflatable penile prosthesis partially inflates with physical activity. It can be minimized by placing the reservoir in the prevesical (retropubic) space and by performing the back pressure test as described previously. The cylinders should also be kept deflated during healing after surgery and when the prosthesis is not being used.
Mentor has a reservoir with a lock-out valve available as an option. Initial experience with this device suggests that it reduces the incidence of this complication.





Medical Management of erectile dysfunction

MEDICAL MANAGEMENT OVERVIEW IN ANDROLOGY:

ERECTILE DYSFUNCTION:

Pharmacotherapy of ED could intervene in the CNS: ALPHA 2 ADRENERGIC BLO0CKERS (YOHIMBINE,PHENTOLAMINE)and dopaminergic antagonist (APOMORPHINE ) or peripherally agents that enhance , elevate or directly stimulates the synthesis of secondary messenger molecules such as c AMP or c GMP and direct activators of adenylate cyclase for ex: Phosphodiesterase inhibitors :non selective –papaverine, Type 5 –sildenafil citrate,vardenafil,Tadalafil,Type 3 Milirinine and Type 4 roliparm
Drugs for treating ED can be taken orally, injected directly into the penis, or inserted into the urethra at the tip of the penis. In March 1998, the Food and Drug Administration (FDA) approved Viagra, the first pill to treat ED. Since that time, vardenafil hydrochloride (Levitra) and tadalafil (Cialis) have also been approved. Additional oral medicines are being tested for safety and effectiveness. Viagra, Levitra, and Cialis all belong to a class of drugs called phosphodiesterase (PDE) inhibitors. Taken an hour before sexual activity, these drugs work by enhancing the effects of nitric oxide, a chemical that relaxes smooth muscles in the penis during sexual stimulation and allows increased blood flow.While oral medicines improve the response to sexual stimulation, they do not trigger an automatic erection. The recommended dose for Viagra is 50 mg, and the physician may adjust this dose to 100 mg or 25 mg, depending on the patient. The recommended dose for tadalafil(Megalis,Forzest) is 10 mg, and the physician may adjust this dose to 20 mg if 10 mg is insufficient. A lower dose of 5 mg is available for patients who take other medicines or have conditions that may decrease the body's ability to use the drug.
None of these PDE inhibitors should be used more than once a day. Men who take nitrate-based drugs such as nitroglycerin for heart problems should not use either drug because the combination can cause a sudden drop in blood pressure. Also patients have severe cardiac diseases like recent Myocardial Infarction, reduced stress tolerance should avoid PDE-5 inhibitors.


















































sildenafil
tadalafil
verdenafil
Maximum plasma concentration
30-120 (median 60)
30-360 (median 120)
30-120 (median 60)
Half life hours
4
17.5
4-5
Duration of action
up to 4-12
up to 36
Up to 4-12
Food restriction
may take longer to work with meals
can be taken with or with out food
can be taken with or without fatty foods
INTRA CAVERNOSAL INJECTION OF VASO ACTIVE DRUGS (ICIVAD)
Many men achieve stronger erections by injecting drugs into the penis, causing it to become engorged with blood. Drugs such as papaverine hydrochloride(15- 60 mg), phentolamine, and alprostadil (marketed as Caverject) widen blood vessels. These drugs may create unwanted side effects, however, including pain (36%) persistent erection (4%) and scarring. It gives a success rate of 70-90 % but these injections have a drop-out rate of 25-60% because of mainly pain or sometimes development of corporal fibrosis.
Methodology of giving papavarine/bimix:
Start with 29-30 G Insulin syringe for the injection therapy.

Papavarine:It can be started with 15 and given till 60 mg. Inject in any corpus.
Bimix: Add chlorpromazine ( 4 ml papavarine to 0.1 ml chlorpromazine combination) start with 0.1 to 0.2 ml and then gradually increased .Again the injection can be given in any one of the corpus
Drug therapy for Peyronie’s disease:
Medical Treatments
Various medications like Vit E 400 mgs three times a day for 3 months, Cochicine 0.5 mg 2 bd for 3 months or Tamoxifen 20 mg BD for 3 months.The placebo controlled trioals have not shown efficacy of the medications but colchicines there are no placebo studies. It seems to be effective.

Researchers have also tried injecting chemical agents such as verapamil, collagenase, steroids, and interferon alpha-2b directly into the plaques. Verapamil and interferon alpha-2b seem to diminish curvature of the penis. The other injectable agent, collagenase, is undergoing clinical trial and results are not yet available. Steroids like triamcilone have caused loss and atrophy of the local tissues and weakening of the tunica. The surgical planes also become difficult after steroid injection.
The intralesional injections are given with 24 G needle making multiple passes through the plaque.There is a possibility that the multiple passes make the plaque weak by mechanical disruption.
Intralesional Therapy:
1) Intralesional Verapamil
Dose 10 mg verapamil/4ml+6mlsaline total 10 ml ;2 weekly for 12 injections
Promising but un proven
2)Intralesional interferon -alpha-2b
Dose: 1millon units 2 weekly for 12 injections
Placebo trial-ongoing
Possibly useful
3)Intralesional Steroids
Dose 40 mg triamcinolone /ml, dilute as per size 6 weeks total 6 injections
Steroids may weaken tunica loss of surgical planes due to trauma

IDIOPATHIC OLIGOSPERMIA :MANAGEMENT


Despite advances in diagnostic modalities up to 25% patients exhibits unexplained infertility. A variety of medical therapies have been suggested to treat this group. However none of these have sown effective to be repeated controlled trials. A meta-analysis of all controlled studies for idiopathic male infertility has failed to reveal significant efficacy of currently available treatment .In the hope that they may be effective in a selective group of people a minimum of 3-6 months trial should be given to include at least one cycle of spermatogenesis
The empirical therapy includes the following drugs:
1) Hormonal agents (direct or rebound effect):The testosterone undecanoate 80-160mg/d, Testosterone enanthate or propionate inj 2-3 weekly Side effects: Azoospermia ,gynecomastia, cholestasis and hepatic dysfunction

2) Antiestrogens : Clomiphene citrate 25-50 mg daily, Tamoxifen 10-30 mg daily, Side –effects: nausea, weight gain loss of libido, headache ,gynecomastia, dermatitis.

3)Antioxidants: The oligospermia is many a times attributed to Reactive Oxygen Species.Various agents are prescribed to nullify the effects of Reactive Oxygen Species like glutathione,Lycopene-4mg/d, Vitamin E 400-800mg/d,N-Acetyl Cysteine 1000 mg/day.
4)Sperm vitalizers : Cellular Energisers like L-Arginine,Zinc, Selenium, proanthrocyanidin , Carnitine 1-2 mg/d CoQ10 10-400mg/d,Pentoxiphylene

If this is unsuccessful ,Assisted Reproductive Technique (ART) is employed or a combined approach may be started simultaneously in older couples.


Specific medical therapy in oligospermia:
Chronic fungal dermatitis
Anti fungal topical cream For ex.Candid B ointment locally

Chronic filarial epididymo-orchitis
Anti filarial &anti-inflammatory drugs-Hetrazan 100 mg three times a day for 3 weeks
Seminal Infections:-
Whether infection causes infertility is still controversial. There are several conflicting reports of benefit of treatment. The semen analysis showing plenty of pus cells should be discussed with the seminologist so as to remove any confusion of round cells with immature spermatogonia. Semen culture should be done in such cases.The common seminal organisms are:Streptococcus fecalis,E coli,Coagulase +ve staph (albus) or Occasionally Klebsilla , proteus,pseudomonas. Ciprofloxacin/doxycyclins can be administered as per the semen culture sensitivity report for a period of 4-6 weeks. As a rule, both sexual partners should be treated at the same time.In the mean time condom intercourse can be performed. At the end of the treatment it should be confirmed that infection is eradicated as there is tendency for chronicity

Antisperm antibodies: The direct test should be done for ASA and if present should be treated on priority with Intra-Uterine Insemination.The other modality of treatment is giving prednisolone 5 mg three times a day for 3-12 months.

Management of hypogonadotrophic hypogonadism:
Management delayed puberty: No initiation of puberty by age 13 in girls and 14 in boys
Delayed puberty Management
Injection testosterone esters are given in the strength of 50-100mg per month for 3-6 months.This This dose will advance puberty without impairing height potential.The spontaneous onset of puberty should be awaited for 3-6 months if there is no initiation formal testosterone replacement therapy should be given.
Management of pre pubertal Hypogonadotropic Hypogonadism

The treatment should be based on androgenising the patient. So it is usually done by giving testosterone or HCG.

Testosterone Replacement Therapy for Androgenisation:
Inj Sustanon deep IM in the following protocol:to start with 100 mg deep intramuscular every month for 3 months.This dosage is progressively increased to 250 mg once a month followed by 250 three weekly for long term treatment. When fertility is desired LH and FSH support is usually given with proper counseling as the cost of the therapy may be 2-3 lakhs with 50 % chance of conception.
The underlying principle is to achieve initial testicular growth with LH (LH is given as HCG. 5000 u one injection per week , 2000 u two to three injections per week.HCG dose monitoring is done by assaying testosterone on Day 3(for response) and Day 7(for sustenance).Testicular volume is monitored along with the signs of androgenisation. When testicular volume become 18 ml and ejaculation starts then FSH are added to complete spermatogenesis.FSH is started in the form of HMG
Dose options:37.5 units thrice-a-week/75 u thrice-a-week/150 u thrice-a-week
This is continued till pregnancies occur. The count may increase from azoospermia to 5-10 millions/ml so Assisted Reproductive Technology may be needed.Testosterone is restarted after pregnancy is over.




Drugs Therapy in Premature Ejaculation
Local anaesthesia: Topical anesthetics/gel are sometimes given with the idea of desensitizing the glans and delaying the orgasm. Lignocaine cream can be given for application for 20 minutes before the sexual act.
Medications:
Normally Selective Serotonin Uptake Inhibitors are used for such patients along with psychotherapy. The mechanism of action of SSRIs is linked to their inhibition of neuronal uptake of serotonin in the CNS. They prolong the sexual climax causing relief from early unwanted ejaculation.
These SSRI (Sertraline,Paroxetene.Fluoxitine)may take until at least 3 weeks following initiation of treatment to cause improvement in sexual latency.
Dose of the medications:
Clomipramine (clonil) 10-25 mg
Paroxetine(parotin) 10-20 mg
Sertaline (sertima) 25-100 mg
Fluoxetine(prodep) 20-40 mg
These drugs may cause side effects like yawning,anejaculation,decreased libido,perspiration and increased fatigue.

It has been seen that many patients with PE have undelying erectile dysfunction also so adding PDE-5 inhibitors like Viagra(sildenafil),Tadalafil works well.
Dapoxetine is an SSRI developed specifically for the treatment of premature ejaculation. Dapoxetine may be effective at first dose (ie, on-demand) for premature ejaculation when given 1-3 hours prior to sexual intercourse.
The optimal medical treatment for premature ejaculation has not been established but single dosing prior to sexual relations can work for many males.While raised blood levels through daily use of the medication may be unnecessary resulting in many CNS side effects. Obviously, if single dosing is successful, therapy is simpler and is associated with fewer adverse effects. Therefore, this may be the preferred initial therapy.
Dapoxitine right now although is manufactured in India ;is not available in market.But it soon expected after Food Drug Administration approves it.


Dosage of the testosterone and diagnostic evaluation:
The level of total testosterone below < 200-250 ng/dl of total testosterone /,8 nmol/L total testosterone or <3.8nmol/L bioavailable testosterone/<0.255 nmol/L free testosterone is indicative of low testosterone level. The actual threshold will vary as per previous levels life styles and habits.
Various types of testosterone replacement:

Testosterone therapy injectable
· Testosterone enanthate (testoviron depot)200-400 mg/4 weekly deep IM
· Mixed testosterone esters (sustanon) 250 mg/3 weekly deep IM
Highly effective inexpensive but causes Wide variations in level so the effect can be erratic like mood variations in the patient.

Oral
Testosterone undecoate (andriol)160mg/day. It should be taken
after full meals.

Gel
Available in 5g to 10g sachets. It is applied to shoulders and chest. After application 15-20 minutes are allowed to dry. The patient should avoid bath or swimming for 6 hours there after. The gel causes physiological levels to be attained without variations. The side effects are skin rash in some.

Spray
4-6 sprays every day. It is applied to shoulders and chest. After application 5 minutes should be given for application. The patient should avoid bath or swimming for 6 hours thereafter as in gel. The gel causes physiological levels to be attained without variations.



Adjusting dose schedule:
Check testosterone level before using the 30 week dose
Testosterone level recommended dosing interval
10-15 nmll/L continue at 12 weekly intervals
<10nmol/L continue at 10 weekly intervals
<15 nmol/L continue at 14 weekly intervals


a)Monitoring during testosterone therapy
b) Monitor for response: Primarily symptomatic, there will be increase in libido, energy and feeling generalized well being. The erectile dysfunction will start resolving. Generalised muscle strength as witnessed by handgrip and cognition will also improve.Bone density will also increase.
c) Monitor for complications: Hyperviscosity syndrome, increase in RBC mass,so complete blood count and hematocrit should be monitored. If hematocrits increase more than 55% then therapy should be stopped. There is a risk of exaggeration of pre-existing carcinoma prostate. The therapy as such doesnot increases the risk of prostatic malignancy. The risk of sleep apnea syndrome is increased as the central response to CO2.Liver Function tests also may deteriorate so need to monitor LFT,PSA,Hematocit.

Nocturnal Penile Tumuscence Rigidity Test: Relevence in Erectile Dysfunction


Nocturnal Penile Tumuscence Rigidity Test:
In its classic form, NPT consists of nocturnal monitoring devices that measure the number of episodes, tumescence , maximal penile rigidity, and duration of nocturnal erections. In 1985, the RigiScan was introduced; it was the first device to provide automated, portable NPTR recording. The device combines the monitoring of radial rigidity, tumescence, number, and duration of erectile events with the convenience of a portable system that can be used at home. It consists of a recording unit that can collect data for three separate nights for a maximum of 10 hours each night (As shown in above Figure). The mechanics consist of two loops: one is placed at the base of the penis and the other at the coronal sulcus. By constricting the loops, the device records penile tumescence (circumference) and radial rigidity at the penile base and tip. Radial rigidity above 70% represents a nonbuckling erection, and a rigidity of less than 40% represents a flaccid penis. The number of erections considered normal is three to six per 8-hour session, lasting an average of 10 to 15 minutes each. The normal NPTR criteria are: four to five erectile episodes per night; mean duration longer than 30 minutes; an increase in circumference of more than 3 cm at the base and more than 2 cm at the tip; and maximal rigidity above 70% at both base and tip.
The documented presence of a full erection indicates that the neurovascular axis is functionally intact and that the cause of the ED is most likely psychogenic.