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PROSTATIC HYPERPLASIA, IMPOTENCY AND MALE INFERTILITY 

As a person becomes older, they are over 60 years of age, more than half of the people would have some evidence of benign prostatic enlargement, whether histologically or clinically. When you reach the age of 85 years, almost 90% of people in this country would have benign prostatic enlargement, again, histologically. You can even find evidence histologically of enlargement of this gland in at least 10% of people in the prostatic hyperplasia.

The histologic evidence of benign prostatic enlargement, even at the age of 30 years. Then it keeps on enlarging and it can become symptomatic, mainly after the age of 50. Similarly, this is also just the prevalence of this gland this slide shows in a graphic fashion in over 1000 autopsies. This is the age range in years here and the number of autopsies done in this particular age.

More classically, the symptoms from a BPH would be an obstructive type. The patient would complain of incomplete emptying of his bladder, intermittent or very poor stream or that he has to strain to empty his bladder. The second part would the irritative symptoms which would be frequency (that he is going more often to the toilet), urgency and nocturia. Most of the time that people come to the clinic saying, "Well, I started getting up at night now, two, three or maybe five.

PSA. Prostate specific antigen. Although it states here it is optional and I think you probably just heard a talk on PSA. Usually people over 50 years. The American Cancer Society recommends that everybody get a PSA after 50 years of age. If they have a high risk for development of prostate cancer like family members or the different ethnic races, then they probably need it at earlier than 50 years of age.

If the urine shows that there are some red blood cells in the urine so there is evidence of microscopic hematuria which could be due to benign enlargement of the prostate, then we do evaluate them just like a hematuria evaluation. We would do some upper tract imaging studies like IVP or an ultrasound and then urine cytology and cystoscopy at the same time.

Other diagnostic tests. You can have Uroflow or you can check post void residual which is whether the patient is emptying his bladder or not. If after he just emptied his bladder in the toilet, you put a catheter in or check by a pelvic ultrasound how much urine he left behind, if it is anything more than 60 cc, that’s an abnormal post void residual. Up to 60 cc, we usually take it as normal because usually people would leave around about an ounce or two ounces of urine behind.

Pressure flow study which is also called urodynamic tests or cystometrogram. A pressure flow study is where we measure the bladder pressures when the patient voids to see what pressure the bladder muscles generate at the time of voiding. At the same time, we measure their flow and the strength of their stream when they are voiding to see if it is normal or not which is the same.

If the patient is symptomatic, then obviously, the first line of treatment these days now has become medical treatment first if their symptoms are not bad. Like we talked about earlier, mild symptoms and moderate symptoms are indications for medical therapy. The medical therapy would be something you want to give to block those receptors we just talked about – alpha-1 receptors. So alpha blockers became the first line of treatment. Those would be your Cardura/doxazosin, Hytrin/terazosin and the new medication we just got approved last year would be Flomax or tamsulosin. Another group of medications would be 5-alpha-reductase inhibitor and we’ll talk about that later which is Proscar or finasteride.

Then another treatment would be what you can classify as minimal invasive treatment which would be transurethral microwave or hypothermia you can also call it. Or TUNA – transurethral needle ablation. These both are minimally invasive therapies. We’ll just briefly talk about the fact that there are mainly alpha-1 receptors over your prostatic capsule or the smooth muscles surrounding the prostate gland. Then they are also further classified into alpha-1a, b, d and there is also 1c.

So now let’s classify those alpha-1 blockers which block those receptors. In the past, we used what we called nonselective alpha-blockers when we did not have any of these newer medications available which was about 15, 20 years ago. Phenoxybenzamine was the one which was commonly used at that time to treat BPH and it would block both alpha-1 and 2. So the alpha-2 receptors are also present over your heart, your lungs, bronchi and smooth muscles and it would block all of those. So there were a lot of side effects from using phenoxybenzamine at that time.

So people thought, "Well, let’s just block the alpha-1 instead of alpha-2. We do not need alpha-2 because they are not present over the prostate." So they came out with these medications – prazosin, alfuzosin – and they were blocking all the alpha-1 receptors. Now, some of the alpha-1s are also present in the heart so we had problems with hypertension. The patients would start feeling dizzy, have partial hypertension, some cardiac side effects.

Then we came out with more refined alpha-1. They are also highly selective but there are alpha-1 receptors only as well which would be Hytrin and Cardura. They also still have cardiac side effects, mainly in the form of postural hypertension. If the patient is already on some antihypertensives for the hypertension, for example, if they are taking beta blockers you don’t want to give them Cardura or Hytrin. You don’t want to block both their alpha as well as their beta receptors because they are already taking beta blockers – Inderal, for example, or Propranolol.

So these are the problems. When they are already on some sort of antihypertensive, we have to talk to their cardiologist or family care doctor to stop their beta blockers. You then switch them to alpha-1 blockers which would take care of their hypertension, too, because they would also have an antihypertension effect as well.

Later on, when they further studied the alpha-1 receptors, we talked about those subclassifcations or subtypes of alpha-1 receptors – alpha 1a, b, d or c, alpha-1a being the most abundant. Then they came out with this medication Flomax/tamsulosin which selectively blocks alpha-1a. This was approved by the FDA last year. So by using tamsulosin or the Flomax, they got rid of hypertensive side effects or cardiac side effects because it selectively blocks alpha-1a. So you can give this medication if someone is already taking anti-hypertensive, you can safely give the Flomax to treat their BPH.

The doses are listed here. There is a starter pack we start with because you never know when the patient may develop postural hypertension so we basically titrate the dose and start at a very low dose – 1 mg to start with. Usually, we tell them to take it at bedtime so that they can just take the tablet and go to bed rather than walking around and see how they tolerate it. If they are tolerating well and if they need more medication, then you can go up on the dose like this. It comes in 1, 2, 5 and 10 mg strength. The same as Cardura except it is 1, 2, 4 and 8. Tamsulosin is 0.4 once daily. It does not require titration because it does not have cardiac side effects.

5-alpha-reductase inhibitor. The testosterone gets converted in the prostate cells to dihydrotestosterone – DHT and this is the enzyme that 5-alpha-reductase helps this conversion. Now, people thought that since the prostate needs DHT for its growth, if you block that enzyme, block that conversion from testosterone to DHT, then you can stop the growth of the prostate and you can even shrink the prostate gland. So this thing came out. 5-alpha-reductase inhibitor or Proscar. So Proscar was used to block that enzyme. Finasteride will block that androgen.

Side effects. It causes decreased libido. The other side effect is it does decrease the PSA. It changes your PSA so one has to be really careful. When the FDA approved Proscar, about in ’92 or ’91, the person has to have the PSA prior to that. Now, medical therapy is not indicated if the person does not have much in the way of symptoms, like less than a score of 7. Then you can say, "I think we should watch you for awhile." So watchful waiting would be the one. Now, we’ll talk about more invasive treatment first. The surgical treatment. If somebody has severe symptoms, then obviously you need a prostatectomy. You can do prostatectomy through a transurethral resection of the prostate or at a higher current,

What are the indications when you think the patient would need prostatectomy? There are certain, what are called absolute indications, and some are relative that you can go either way. The absolute indication would be that patient who has deteriorating renal functions. You don’t want to wait or hang around anymore. Then you would definitely want to go ahead and take care of it. So if the patient has some sort of renal insufficiency or renal failure or they are in chronic retention. Retention is also one of those. It’s probably not listed here but it just says high post void residual here or they are in retention and they are having overflow. So they are in chronic retention. If the person is having recurrent episodes of urinary tract infections. Now, there will be a risk. If you don’t do the TURP, they may become septic and they may come into something like urosepsis with a high

If somebody’s having recurrent hematuria in which you have ruled out other causes of hematuria like any urethral cancers, stones, prostate cancer, for example, then we probably would presume the patient is bleeding because of the benign enlargement

Transurethral syndrome. We use fluid when we are dissecting. The most common fluid used is glycine and sometimes what

Laser prostatectomy is not as popular now as it used to be when the laser came out about five years ago. They are very expensive. One probe, one time use only, is $800. Not very effective in the long run. There are some problems in the short term too as well because it sloughs out the prostate tissue and they keep voiding that slough tissue over a few days and weeks. In the short term, though, they do effectively relieve the symptoms.

Advantages. You can do that if the patient has multiple medical problems. If they’re on Coumadin or they’re on anticoagulation, they may bleed if you try to resect their prostate gland. Then this will be the option because definitely the bleeding is less than your regular TURP.

Microwave or hyperthermia. Now, you can heat the prostate gland and there are some heating patterns. The temperature maximum you can attain is between 42-45ºC. You can use either transurethral heating or transrectal. Both probes are available to heat the prostate gland. It’s basically microwaving it or cooking it.

There is a machine called Positron single session. It can be done under local anesthesia. That’s the main advantage. It is also not very good – not as good as other therapies. This is your probe used for hyperthermia and this is the machine. The patient just lies down here. It doesn’t look like a microwave.

Balloon dilations of the prostate urethra, mainly. Again, there were some studies done in which the Omaha VA was a part of

There is also prostatic stent. You can put stents in the prostatic urethra for the same reason – to keep the prostatic urethra open. The Urolume is the one stent that was approved by the FDA mainly for the urethral stricture disease, not for the BPH but it has

I think now we’re going to change to erectile dysfunction which is a more popular topic these days. This is just a definition of impotence and I need not go over the definition of impotence. Prevalence. It was on the front page of the Omaha World Herald today there was an article on erectile dysfunction. I think it mentioned about 3 million people have erectile dysfunction although only 10% show up in the clinic or seek clinical treatment. Here it gives you the prevalence. Between this age group, around 40 onwards and between 70, there will be more incidence at the higher age group, like 67%. Your minimal erectile dysfunction

Other diseases like Peyronie’s disease or scar tissue of the tunic albuginea which line the penile shaft or the corpora cavernosa can also produce erectile dysfunction. The main thing it does is creates a curvature of the penile shaft but at the same time they may not get a good erection as well. Also, we do a focused neurological exam. We know the spinal segments which that nerve supplies belongs to S2,S3, S4. So what we basically do, which would be your perianal area to examine, is we check the 

This is the penile curvature we just talked about – Peyronie’s disease. This is a dorsal curvature – upside. It can be on the right side, left side. It can actually be a ventral curvature. It

Then hormonal evaluation. Basically, all neurologists all agree, I think, that instead of ordering a bunch of blood tests or other tests, the only thing that is important out of these hormones would be testosterone. If the testosterone is low, then sometimes it is possible that the patient may have hyperprolactinemia. Then I 

Medical therapies. A lot of talk is going on about this. Viagra. This tablet just got approved by the FDA a couple of weeks ago. What this tablet does is it blocks a phosphodiesterase enzyme. This particular medication blocks the type 5. What it does is usually there is another substance – cyclic GMP – which is required for the smooth muscle to relax and then it usually breaks down to a different product. What it does is this enzyme phosphodiesterase helps in that breakdown. So if you block that enzyme, it would keep that cyclic GMP which is important for the relaxation of the smooth muscles there which is required at that time. So if you try to avoid the breakdown of that substance, you can keep the erection or you can produce erection. So that’s how this was discovered.

Its effect is dose dependent. It comes in 25 mg, 50 mg and 100 mg tablets. With 25 mg – which is the lowest dose – there is about a 63% success rate for producing erections. If you go up on a dose to 50 mg, about another 10% more to 72%. Then with 100 mg, it’s 80%. People have tried more than 100 mg and it 

Trazodone, which is in a different class of antidepressants. It does have effects of potentiating erectile function. The good thing about sudanophil as compared to the other modalities is it does not create priapism which was a problem when we didn’t have this medication, when we were using injections, for example. We used to warn the patient that if the erection stayed for more than four hours he needed to come back so that you could reverse it. There is no problem or priapism with Viagra so it is definitely good in some respects.

Other treatments. Self injection is still used. Caverject is the most common one. Pavarine is another one. Phentolamine is another one. They are trying phentolamine in a tablet form as well these days on the Phase III trials but, again, the problem is they have to be taught how to inject into their corpora and priapism would be a problem since some people don’t want to inject themselves.

Muse which also became popular at one time. There’s a delivery system. You put it in the urethral meatus. The medicine goes in there, gets absorbed. You have to massage for at least 10 minutes. It takes about 10 minutes to get the medicine into the 

Infertility problems. Male factor. Basically, about 15-20% of married couples are infertile whether they do seek any treatment or not. What we usually define it as is if somebody had unprotected sexual intercourse for at least a year, then you classify it as primary infertility. There’s another term – secondary infertility – that they had a child and then now they haven’t had the second child that they want. So they have been doing intercourse for about a year and they can’t have a second child so they have a secondary infertility.

There are different reasons. There could be a female factor for infertility. About 50% which is pretty high. Half of the problems have to do with females and about one-third male. Another 20% would be both male and female.

These are just causes of infertility. Varicocele. Very common. Idiopathic. We have never found any cause in the patient. Testicular failure, again. Obstruction to the transport of the of the sperm, either in the vas or in the ejaculatory duct itself. Cryptorchidism. The patient had undescended testicle. Now the problem of agglutination, volume is low, sexual dysfunction, ejaculatory failure and some endocrine or hormonal problems.

Sexual history. You will ask them if they have a normal libido, do they have normal penetration and are they using any lubricants. Sometimes some of them are spermicidals.

Childhood history. They had undescended testes when they were born. If they had any problems with torsion when they were an adolescent, an injury to the testicle, when did they have puberty. All this history. Any trauma, any pelvic trauma.

Surgical history. You ask if they have had the bladder neck operated on because we talked earlier about the sperms, instead of coming out, they may go back retrograde into the bladder if they have had any operations. Usually, young people won’t have TURP but they can have some operation on the bladder neck when they were a child.

Hernia repair as a child can damage the vas during the hernia repair or may cause damage to the testicular artery. The blood supply to the testicle can damage the testicular function later on in life. History of infections. Bilateral mumps can cause infertility later on life. TB. Not very common here.

Drugs can cause this. Any drugs which can affect your pituitary gonadal axis. Antiandrogens. Mainly cimetidine is the most commonly used drug for this purpose. Your steroids can do that. Prolactin. We talked about hyperprolactinemia for impotence. It can also cause infertility. So it 

Sperm counts. While some people take 60, these days more than 40 million/mL would be the normal accepted range. Whether they are moving and, in motility, actually forward progression is more important. Then morphology – whether it looks normal or not. More than 60% should look normal. If they have infection, you can see the white blood cells in the semen.

It affects sperm production. We talked about in the collection of these sperms that basically it takes 60 days for sperms to mature and to get transported out

Treatment. Again, it depends on what etiology or what the cause of the infertility is. If the patient has a varicocele, you can repair it surgically. If the patient has obstruction, what you do is a transurethral resection of the ejaculatory duct for this problem. Or if they have an obstruction more proximal, like towards the vas, then you do vasovasostomy and you bypass that obstruction. This is like after vasectomy if the patient wants to have children again, you take out that segment you cut out and then you rejoin them – vasovasostomy. Or even if the obstruction is even much more proximal. Epididymal vasotomy where it actually goes directly with the epididymis. Or if it is irreparable, then you can aspirate sperm directly from the epididymis and then you can have in vivo fertilization and those types of 

If the patient, as you notice, you can order a sperm analysis and if you find a lot of clumping or agglutination, they may have antibodies. 40% of the people after vasectomy develop antisperm antibodies. If you notice, you can check the level of those antibodies in the blood as

Varicocele. 60-70% would improve in their sperm counts and motility. But look at the fact that there is a 40% pregnancy rate after you repair the varicoceles.