Interview: Dr. Goldstein - Penile tissue changes reversible (via androgens)

VIEW ONLINE: … ?id=111998

Dr Irwin Goldstein corroborates the fact that androgen replacement can reverse penile tissue fibrosis, and that lack of androgens cause progressive fibrosis via collagen deposits… and that these changes can lead to vasculogenic impotence. Also corroboration of the animal studies in the “Finasteride” and “Other” studies of that show these changes!

NOTE: One of our own members, AntCraven, experienced penile tissue changes after Propecia left him with low T/DHT levels - read his resolution post in the Personal Profiles section:


ED: What to do when pharmacotherapy fails
May 1, 2003
By: Culley C. Carson, MD, Irwin Goldstein, MD, Raymond C. Rosen, Phd, Ajay Nehra, MD
Contemporary Urology

ED: What to do when pharmacotherapy fails

Major advances have been made in the treatment of erectile dysfunction (ED) in the past 2 decades, especially with the revolution begun by the introduction of the first effective oral agent, sildenafil citrate, in 1998. However, as many as 30% of men will not respond well to oral agents. As a result, a significant group of patients will need some other form of intervention to make them sexually functional. This panel discusses a variety of options—standard, new, and experimental—for patients who present for further therapy after initial oral therapy has failed.

—Culley C. Carson, MD,
Carson: Let’s begin by discussing why treatment with sildenafil citrate [Viagra, Pfizer] might not be successful in some men. Dr. Rosen, what are some of the reasons you’re aware of.

Rosen: The issue of sildenafil failure is a bit more complicated than it first sounds. In the traditional sense, failure means that the medication does not result in an erection that is sufficient for intercourse. Men who fall into that group can be further categorized into those who never achieve the degree of rigidity or firmness necessary for intercourse and those who do achieve it on some occasions but don’t reliably achieve it.

A second group of “failures” consists of men who don’t take the medication under appropriate circumstances; for example, they may take it after a full meal or with alcohol. A very common problem is that patients fail to get sufficient sexual stimulation before attempting intercourse. Of course these types of failures are more likely to occur among men who have not received adequate patient education.

Finally—and here we get into the question of whether this really constitutes failure—are men who achieve an adequate erection but discontinue the medication because they aren’t satisfied with the results for a variety of personal reasons such as partner issues, dissatisfaction with the lifestyle aspects of the medication, or its costs.

Nehra: While it’s unrealistic, some patients expect sildenafil to restore their erectile function to a level comparable to the peak levels they experienced in their 20s and 30s. There are also some patients who have satisfactory results with sildenafil initially; however, over the next 2 to 3 years, they may notice a progressive decline in function despite optimization of oral therapy. It’s important to educate these patients and counsel them with respect to the progression of vasculogenic ED, which along with any comorbidities they may have, may be causing medical therapy to fail.

Goldstein: There is also the issue of side effects from phosphodiesterase [PDE]-5 inhibitors. The more simple side effects include flushing, headache, and nasal congestion. But, in my practice I’ve seen men with varying complaints, such as dyspepsia and blue vision, who get sufficiently annoyed that they won’t take the medication. Often, men who don’t achieve good erections will discontinue the medication because of these types of side effects, but even some who have a reasonable response may stop taking it. Actually, the dropout rate is substantial. More than half of men who start therapy don’t refill their prescriptions.

Carson: The dropout rate may be a condition-specific issue because it is nearly equivalent to the rate seen with injection therapy and other therapeutic alternatives. I think the dropout rate with counseling alone is quite high, probably more than 50%. Similarly, the dropout rate for alprostadil, both injectable [Caverject, Pharmacia & Upjohn; Edex, Schwarz] and intraurethral [MUSE, Vivus Inc] is extremely high. I’m not aware of any data on the dropout rate with vacuum erection devices, although I imagine a lot of them are gathering dust in people’s closets.

Goldstein: The high dropout rate is puzzling. We now have a pill that can improve erections—one of the most sought after discoveries in the history of mankind—and people are either afraid to take it or are embarrassed to ask for it or doctors are embarrassed to bring it up or ashamed, or guilty, or whatever.

Role of psychological intervention
Rosen: The high dropout rate may be related to patients’ unrealistic expectations about how much a pill can do. If a man is just given a pill with very little else, it’s unrealistic for him to expect that it will improve his relationship with his partner or improve his partner’s sexual feelings or sexual functioning. That’s where counseling can be beneficial.

Carson: Are there data supporting the use of counseling in addition to pharmacotherapy?

Rosen: We’re just starting to see evidence. So far, it seems that adding counseling—either individual counseling for the man or couples’ counseling—improves compliance, satisfaction, and outcome. People report feeling better about the couples’ relationship, about the woman’s sexual functioning, and so on.

Carson: Are there also data to support the addition of sildenafil to counseling, to make counseling more effective?

Rosen: Yes, reports are just beginning to be published. Either way, having a PDE-5 inhibitor in the mix is a huge advantage.

Goldstein: Counseling makes sense intuitively because this field is so intrinsically linked to the mind. We presented data here on how ED affects quality of life.1 It’s exciting that we finally have data demonstrating that romantic relationships suffer, family relationships suffer, and employment suffers. So, as Dr. Rosen mentioned, simply prescribing a pill only deals with one aspect of a complex problem.

Nehra: Counseling is an intriguing and important tool in the overall therapy and eventual success of treatment for both the patient and his partner. Counseling combined with a PDE-5 inhibitor seems to also offer a huge advantage over either method alone. Emerging evidence is showing that patients who have received penile prostheses in conjunction with counseling have significant patient and partner satisfaction profiles. In the near future, prospective data that provides an accurate assessment of the potential role of counseling in conjunction with other therapeutic measures should be forthcoming.

New concepts in androgen deficiency
Carson: We all agree that education and counseling are appropriate components of ED treatment. But, let’s move beyond the psychological issues. Dr. Nehra, what role do androgens play?

Nehra: It has been shown that by increasing levels of testosterone, we can increase both nocturnal and spontaneous erections. Particularly interesting is the fact that this improvement occurs over a period of several months rather than occurring immediately. This suggests that the hormonal milieu may result in restoration of the erectile tissue over time.

Goldstein: We have burgeoning new data on how androgens modulate erectile physiology. This is completely fascinating to me because I grew up in the era when, at lectures, you would hear statements like, “My 2-year-old grandson, who I know has essentially castrate androgen levels, has erections that poke through the crib. So I must conclude that androgens have nothing to do with erections.” I still don’t understand how children, who have castrate levels of androgen, produce erections at the level of adults who have been exposed to puberty, but the data show that I can rescue sildenafil failures with androgens.

Carson: That’s an important concept—hypogonadal androgen failures can be returned to the minimally invasive therapy of sildenafil just by normalizing their androgens. The animal data are pretty clear that nitric oxide synthase [NOS] in the smooth muscle cells of the corpus cavernosum is influenced by androgen levels.

Goldstein: That data is in the rat?

Carson: Correct.

Goldstein: We’ve done a lot of rabbit research and have found that androgen replacement doesn’t change NOS.

Carson: Doesn’t it change smooth muscle relaxation?

Goldstein: There’s no question that it changes the smooth muscle cell function, but it doesn’t necessarily change the level of NOS. Although we don’t understand why, we’re finding that androgen deficiency Is associated with progressive fibrosis. In essence, because collagen is synthesized from the smooth muscle cell, it’s related, at some level, with that balance of oxygen and fibrosis. But we have animals that don’t get erections whose enzyme levels of NOS are relatively intact, yet the impotence is genuine.

Carson: Are these castrated animals?

Goldstein: Yes. And when we replace the androgen, we can see the histology go from fibrosis back to normal smooth muscle, which is totally amazing. We’re developing a new hypothesis—that endocrinologic impotence equals a reversible form of vasculogenic ED. This is a new concept, and we need to do a lot of work to develop it. Conceptually, however, replacing androgens re-establishes vascular integrity at some level. That’s a huge new role for androgens. Currently, when a man with ED comes to the office, most physicians perform a history and physical and then give him a prescription for sildenafil. But we do a PDE-5 test first. If he fails the PDE-5 test, universally, we give androgens. It’s phenomenal how abnormal their androgen levels are. They’re usually either significantly outside of the normal range or in the lower tertile or quartilea very common finding in sildenafil failure.

Carson: Do you replace their androgens?

Goldstein: Yes, but not necessarily with testosterone. This is another example of how our understanding of androgen physiology has broadened. There are many people whose pathology isn’t only testosterone or isn’t even testosterone, but it’s really at higher levels of androgen, such as dehydroepiandrosterone [DHEA] or 5-androstenedione. So we measure each of the 7 androgens to determine the exact pathology.

It has recently been shown that you can enhance relaxation of coronary arteries by having adequate DHEA levels. A Rancho Bernardo study published in 1987 in the New England Journal found a higher incidence of heart attacks in men with low DHEA levels,2 and no one ever understood why. Then in 2002, an article in JACC finally showed DHEA receptors in coronary arteries. It uses cyclic guanosine monophosphate [cGMP] pathways to cause relaxation. There are also DHEA receptors in the skin. So now we know that androgens that we’ve never thought of as being important are involved in bone, skin, and cardiovascular tissues. This is an interesting area that’s just exploding.

Nehra: Androgens remain an important aspect of erectile function and they are currently being investigated in patients with vasculogenic ED. Restoration of smooth muscle function and smooth muscle tone, while not changing, may have important contributions in the field of vasculogenic ED. This is an area that is currently being evaluated in a number of laboratories and prospective clinical trials. I look forward to some compelling data in the short-term.

Additional options for combination therapy
Carson: Normalizing androgens or adding DHEA is certainly a combination therapy as is combining counseling with an oral agent, but what other combination therapies can we use? Karl Andersson studied sildenafil plus apomorphine in laboratory animals and demonstrated that combining the 2 agents had an additive effect.3 Dr. Nehra, what can you tell us about your study combining intraurethral alprostadil and sildenafil.

Nehra: We studied patients who had undergone nerve-sparing prostatectomy and had failed sildenafil therapy.4 We were able to salvage these patients by using intraurethral alprostadil in conjunction with sildenafil. These patients were captured through a combination of cyclic nucleotides, cyclic adenosine monophosphate [cAMP] and cGMP, respectively, for prostaglandin E1 [PGE1] and PDE-5 inhibitors. The data is appealing because these men represented a highly motivated subset of patients who did not want to try penile injection therapy and instead felt that the combination of sildenafil and intraurethral therapy improved their erections significantly, enabling them to achieve vaginal penetration. We monitored these patients for more than 24 months and found that nearly all of them were utilizing the combination for the desired effect.

Goldstein: Mydlo also showed that a combination of intraurethral therapy and sildenafil can resuscitate either alone.5

Rosen: Manuel Mas’ group from Tenerife, Spain presented a very interesting paper.6 They were administering intracavernosal injections, not along with the sildenafil, but as a priming dose once or twice a week to men who had failed sildenafil alone, and they found that the rate of response to the sildenafil improved dramatically.

Carson: More and more studies are showing that the use of injection therapy helps “normalize” abnormal erections. I think the first was Montorsi’s study that looked at injection therapy after radical prostatectomy.7 It’s a nice concept, but it doesn’t support the use of sildenafil for that purpose.

Rosen: I think the issue of combination therapy is going to be very important in the next few years. If you look at the treatment of other conditions, such as hypertension and depression, combination therapy is the rule—not the exception. In fact, the large majority of patients with hypertension are managed with multiple medications.

Goldstein: Do you envision using multiple PDE-5 inhibitors?

Rosen: Usually in hypertension or in depression, the drugs used for combination therapy typically have different mechanisms of action, which provides more synergy.

Goldstein: So you would use a PDE-5 inhibitor with a central nervous system drug or an -blocker or something like that.

Rosen: Yes. That’s correct.

Carson: The data now show that angiotensin-converting enzyme [ACE] inhibitors enhance erectile function, so an ACE inhibitor and a PDE-5 inhibitor might be an effective combination.

Rosen: Yes, or a PDE-5 inhibitor with an angiotensin-receptor blocker. However, I think a missing piece in this discussion is safety issues—particularly their potential hypotensive effects, because most of these agents are hypotensive to some degree. Certainly with dopaminergic agents you can get sudden dramatic syncope and hypertensive effects. So before combining agents, even with intraurethral therapy, I think we need some good safety studies to clarify the potential risks of certain dosage levels and combinations. I do believe that, in time, combination therapies will be very common—perhaps even the rule—in this field, particularly if we find that the risks are very slight or minimal.

Dosage adjustments

Goldstein: In sildenafil failures, have you ever recommended that patients take the pill at night to see if you can stimulate their night-time erections so their erections for intercourse work? We conducted a study where we monitored nocturnal penile tumescence and demonstrated an increase in night-time erections.

Carson: Yes, we’ve tried that, anecdotally, in a few patients and found the same thing—an increase in nocturnal erections even in patients who didn’t get good sexual response to sildenafil.

Rosen: Christopher McMahon described a large case series showing that when you start with 200 mg of sildenafil, you get an increased rate of adverse effects but no real difference in efficacy.8

Carson: Yes, the efficacy plateaus.

Rosen: But what McMahon found—and anecdotally we’ve observed this too—is that about 60% of patients who’ve been on sildenafil for some time who are not responsive at 100 mg can be salvaged if the dose is gradually titrated up to 150 or 200 mg. However, about 30% of patients had significant side effects. While he did lose some patients due to side effects, there was a net gain of about 30% who would not have been responders.8

Carson: The side effects decline over time, so perhaps even in that situation, if a patient responds to 200 mg with some side effects, it might be reasonable to bring him through that side effect period with analgesics.

Goldstein: In patients like that, I think it’s best to check his androgens. That may be a better way to go.

Intracavernosal and intraurethral therapy
Carson: Let’s say you’ve normalized his androgens, pushed his sildenafil to the maximum dose, and provided education and counseling, but he’s still not responsive. Dr. Goldstein, what’s your next step?

Goldstein: We have about 6,000 people in an injection program. We’re very strong believers in injection therapy, and we’re very careful about the combinations we use. There’s only one FDA-approved substance, which is alprostadil in the form of Edex or Caverject, but we don’t use it very often. We prefer to work with the patient and individualize the therapy. The erectogenic drugs that we presently use are papaverine hydrochloride, PGE1, phentolamine mesylate, and forskolin, which is used in patients with radical prostatectomy, primarily in diabetics and alcoholics. We’re finding that lowering the PGE1 dose used in a routine trimix from 100 µg to 50 or 25 µg per 10 mL stops the pain. We can also increase response by increasing the dose of phentolamine from 10 mg to 40 mg per 10 mL.

PDE-5 inhibitors are great erectogenic agents as well. While we’ve used intracavernosal sildenafil, we reserve that for patients for whom penile implants are the only other option but who want to see if we can restore their erections without an implant. These patients are approaching the end run, and we work with them. It’s amazing how successful this is. We have some people who take sildenafil and injection therapy, too. Erections in patients using injection therapy can also be improved by normalizing the androgens.

Carson: I agree that the trimix concept is the best because you’re relaxing smooth muscles using different pharmacological approaches, which allows the use of lower doses of the various agents. In spite of the benefits, however, I usually start with Caverject simply because a number of my patients live in rural areas or in places that don’t have a compounding pharmacy nearby, or they don’t have insurance coverage for things other than Caverject.

Goldstein: Isn’t the needle size relatively large—27F?

Carson: They’ve changed it to 30F now. Even when the needle was larger, I prescribed insulin syringes.

Nehra: Here again, it’s important to stress the importance of appropriate counseling in conjunction with the use of any therapeutic regimen. Initially, most patients are apprehensive when introduced to the concept of penile injection therapy. However, as these patients are educated and taught how to perform self-injection, the level of apprehension and anxiety rapidly dissipate. Also, while there is a large body of evidence suggesting that trimix is, indeed, superior in maximizing relaxation of corpora cavernosa, both Caverject and Edex are FDA-approved monotherapies for intracavernosal injection.

With respect to the pain issue, the use of a 30F needle has indeed improved patient compliance. However, if a patient using intracavernosal Caverject or Edex therapy has significant pain, I have no hesitation in recommending trimix, since the use of triple injection therapies has a significantly decreased level of pain compared with monotherapy. This has to do with the volume and dose of PGE1 since it is well established that a higher concentration of PGE1 may activate the pain receptors.

Goldstein: Jeremy Heaton tried another approach.9 He administered a low dose of sodium nitroprusside, about 15 µg, intracavernosally with PGE1 to men who had pain. Sodium nitroprusside activates cGMP, which cross-talks to cAMP in an inhibitory way. So by giving the men PGE1 for the erection and sodium nitroprusside to inhibit cAMP, they were getting erections without pain. Of course, if sodium nitroprusside is exposed to light, it decomposes, so he had to wrap the tubing with silver foil, then put the syringe in and quickly inject it.

Rosen: That was the first time I’ve heard of sodium nitroprusside being used as an erectogenic agent. It makes so much sense because it’s a big nitric oxide donor.

Carson: Do you use intraurethral therapy at all in any of your patients, Dr. Rosen? Is that something that you use regularly?

Rosen: At our center, we use almost no intraurethral therapy.

Goldstein: I find that a lot of general practitioners use intrarethral alprostadil. They offer it to their patients as another noninvasive option when sildenafil fails.

Carson: Generally, we don’t use intraurethral therapy, but I do use it in patients who have problems with their penile implants. I think it does a terrific job inducing glans engorgement in patients who complain that their penis feels cold when they’re having sex, which is a common complaint from men with penile implants. If you start with a low dose—250 µg—the patient doesn’t experience a lot of pain but will get enough glans engorgement so that his penis feels warmer.

We also use intraurethral therapy for patients who have failed penile implants but whose insurance company won’t pay for a revision or who don’t want a revision. We’ve had patients in that situation respond to intraurethral therapy with good erections. While the penile implant doesn’t work, the MUSE gives them a functional erection.

Rosen: I agree with Dr. Goldstein. At our center, the urologists I work with often use injection therapy in patients who are pharmacologically unresponsive or who are post-radical prostatectomy. It’s unfortunate more research isn’t being done. While there has been some research on better erection systems and more patient-friendly ways to administer injections, I believe it’s still an unmet need.

Carson: Yes, and we need more work on new drugs too. We did a very nice phase I trial on a potassium channel opener that worked very well and was well tolerated. A major advantage was that there was no pain on injection. Even more important, it didn’t need to be refrigerated, making it much more convenient. Unfortunately, the pharmaceutical company doing the trial didn’t think that there was a market for it.

Rosen: It seems as if the availability of PDE-5 inhibitors has discouraged the manufacturers from further development of injection therapy, which is unfortunate.

Venous leak
Carson: Let’s move on to surgical procedures. Dr. Nehra, are you doing any more venous ligations?

Nehra: No. Venous ligation surgery hasn’t been performed for many years in the United States. Significant alterations in the penile smooth muscle content in patients with mild, moderate, and severe venous leak has been well established.10 With these alterations occurring locally, venous ligation surgery has been shown, in numerous studies, to produce less than ideal results.

Goldstein: I won’t admit to having performed any since 1990.

Carson: I haven’t done them in a long time either. That era has come and gone because the concept of doing penile vein ligation has lost its meaning. The smooth muscle abnormalities that we were probably treating with penile vein ligation are now better treated with drugs. Having said that, what do you do when a patient has failed sildenafil and his dynamic infusion cavernosometry or cavernosography or Doppler ultrasound demonstrates a venous leak?

Goldstein: Androgen injections would be our more logical step. There’s great data from Aversa and colleagues in Rome, Italy.11 Their group has done unbelievable research supporting the concept that ED caused by endocrine abnormality is really a reversible vasculogenic impotence. In one study, they performed duplex Doppler ultrasound studies. On the morning of the ultrasound, they also performed hormonal evaluations—testosterone, free testosterone, and so on. And they found a very strong inverse correlation between the end diastolic volume and the free testosterone.

In the rabbit model we’re developing, once you castrate them, they somehow develop venal occlusion, and there is a lot more scarring. I’m sure the smooth muscle is not working well. If you add androgens, there is some activation of collagenase, which makes the smooth muscle better, makes the tissue look more normal, and helps eliminate the venous leak. We’re showing, in an animal setting, that this is a reversible form of vasculogenic impotence, but Aversa is showing that in humans. There’s something important here that we don’t fully understand.

Penile prostheses
Carson: What do you do if androgen replacement fails?

Goldstein: We implant penile prostheses. We’re doing far more implants now than we ever have. Last month we did 8. We haven’t done 8 in a single month in many years. The story about implants is really very exciting, but it’s not reaching a lot of the practitioners who don’t do them. The manufacturers have put a lot of time and effort into their products. They’ve changed the pumps, they’ve coated these items with anti-infectious agents, and today, the failure rate is remarkably low.

Nehra: In patients who have failed oral therapy, injection, vacuum erection devices, or a combination, there is definitely a role for penile prostheses in the armamentarium. Satisfaction rates for both the patient and his partner are high. In addition, modifications to these devices have enabled them to last for a significant amount of time after initial placement.

Carson: Yes, that’s true. The devices used today are made out of much more durable materials than older devices, and the mechanical malfunction rate is now less than or at least equivalent to that seen with malleable prostheses. I recently heard that of all the prosthetic devices implanted, the genitourinary prostheses—the penile prostheses—are the most reliable. They’re also less often associated with complications than orthopedic-related devices, cardiac devices, and breast prostheses. Now that the device makers are coating them with antibiotics or something inhospitable to bacteria, the infection rates have gone down substantially, from 3% to under 1%.12 Infections were the most serious complication for any of these patients, with the greatest cost. If you look at the overall expense of penile implants, probably the greatest cost is associated with caring for a patient with an infected prosthesis.

Nehra: Yes, infections are a well recognized consequence of any surgical procedure. However, recent data reveals dramatically improved infection rates even in patients at high risk of infection, such as those with diabetes mellitus or who are undergoing reoperation procedures. I usually reserve the new products with antimicrobial coating for patients at high risk for infection.

Carson: One interesting thing we’ve seen is that the infections occurring today are not caused by the agents that used to be the most common culprits—Staphylococcus aureus and S epidermidis. We’re about to report findings from a study in which we repeated what Karl Montague did a few years ago13—we cultured all parts of the prosthesis in patients undergoing a revision and found that more than 50% of them had bacteria colonizing.

Goldstein: Where is the bacteria found?

Carson: On the surface of the prosthetic device we’re removing.

Goldstein: There are bacteria present, but there’s no infection?

Carson: There’s no infection. Because of this, we’re performing Mulcahy irrigations on all patients we revise. I think combining irrigation with the antibiotic-coated prosthetic devices will minimize our infection rates.

Goldstein: How do you explain the presence of bacteria but no infection?

Carson: No matter what type of prosthesis is used, most device-related infections occur 12 to 18 months after the prosthesis was placed.

Goldstein: So the bacteria are indolent?

Carson: Yes. The majority of the literature on this is in the field of orthopedics, obviously because they put in 2 million prosthetic devices per year in the United States. The majority of those bacteria are like S epidermidis. There’s no way that bacterium could get around a prosthetic device by vascular seeding. So those are probably indolent infections. In fact, Lowell Parsons conducted a study in which he replaced the prostheses of patients who had unexplained pain in their implants but no sign of infection—no elevated white count and no demonstration of problems on physical examination.14 The pain resolved, and bacteria were found around the prosthetic devices that were removed. So it’s an indolent infection that’s sitting there causing pain, but not enough to be clinically apparent as a prosthesis infection.

Goldstein: Unfortunately, there is a dark cloud looming over the penile prosthesis world. As of January 2003, Medicare refuses to pay for them. It is unclear how this will impact our field just when penile prosthetic surgery is on the rise and when the devices are more in tune with our needs for our patients.

Carson: The patient satisfaction rates are high as well.

Rosen: What was the rationale?

Carson: Refusal to pay is a bit of an overstatement. They’re actually going to give us a package reimbursement, but that package reimbursement is less than the cost of the device itself. Basically, that package cost includes everything except the surgeon’s cost and the anesthesia fee. So, the hospital and the surgeon have to eat the difference.

Goldstein: They’ve already reduced reimbursement for 4 consecutive years. This is a huge dark cloud.

Vacuum erection devices
Carson: Dr. Rosen, do you use vacuum erection devices at your center?

Rosen: We probably have fewer than 20 patients who use vacuum erection devices.

Carson: Does the same apply for constriction rings?

Rosen: Yes. My sense is that as the number of oral agents increases, there’s a corresponding drop in the attractiveness of the vacuum erection device. I think men who really just couldn’t bear the thought of injections and who weren’t ready for surgery were the primary users of vacuum erection devices. Obviously, oral therapy is far more attractive to the large majority of those men.

Goldstein: There’s a huge requirement for education with the vacuum erection device. A man’s initial reaction is often, “I can’t believe I’m doing this.” Once they get that education, there’s a high rate of satisfaction.

Carson: That’s true. I offer this option to patients but they rarely take me up on it. I use vacuum erection devices most often for patients with Peyronie’s disease and for patients who have had explants for penile prosthesis infection. The device seems to soften the tissues and make the penis a little longer, which allows the surgeon to implant a slightly larger prosthesis.

Rosen: We haven’t really experimented with this, but I’ve heard reports about combining vacuum devices with PDE-5 inhibitors. Has anyone here had experience with that?

Carson: I have a few patients who’ve done that on their own, but I have no studies to suggest that it makes sense.

Goldstein: We love vacuum devices for men who have priapism or following radical prostatectomy when patients complain that their penis is short. It works very well as a penis stretcher. After infection on a penile implant it’s mandatory— it’s like an exercise for them.

Carson: There’s no standard technique. We tell patients to inflate the device to their tolerance every day for 5 to 10 minutes without the constriction ring. The constriction ring itself is good for maintaining the erection for sexual intercourse, but can cause some side effects. In fact, there is an increased incidence of Peyronie’s disease in patients who use the constriction ring regularly. So we advise them to use the device without it. If they have penile skin edema, which many of them do, I tell them to use it every other day until that goes away. As Dr. Goldstein mentioned, using this device does increase the length of the penis; there’s no question about it. It’s better than penile weights!

Beyond sildenafil Carson: While the majority of men with ED are successfully and safely treated with oral pharmacotherapy, usually with sildenafil and soon with other PDE-5 inhibitors, these agents are not successful in all men. Many do not respond to PDE-5 inhibitors, others experience side effects, and still others cannot use this class of agents because they are taking nitrate medications. In these select cases of ED, it is necessary to offer second- and third-line treatment alternatives. These treatments are generally well tested and were used for many years before sildenafil was introduced. These treatments include injectable and intraurethral alprostadil and multidrug mixtures of injectable agents to relax the corporeal smooth muscle through a variety of pathways.

Androgen assessment and supplementation in the hypogonadal man is also an important consideration. Psychosexual counseling and coaching from the urologist is also beneficial for the patient and his partner.

When noninvasive alternatives fail or are not satisfactory, vacuum erection devices may be offered to selected patients. Ultimately, penile prosthesis implantation may be the treatment that offers the best long-term solution for some men with ED. These surgically implanted devices are effective and safe, producing few adverse events and high levels of patient satisfaction.


  1. Goldstein I, Godek LM, Gengler LA. Health and quality of life among men with and without erectile dysfunction: a US population-based study. Int J Impot Res. 2002;14(suppl 3):S17. Abstract C1.1.

  2. Barrett-Connor E, Khaw KT, Yen SS. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986;315:1519-1524.

  3. Andersson KE, Gemalmaz H, Waldek K, et al. The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rate. J Urol. 1999;161(5):1707-1712.

  4. Nehra A, Blute ML, Barrett DM, et al. Rationale for combination therapy of intraurethral prostaglandin E(1) [PGE] and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy. Int J Impot Res. 2002; 14(suppl 1):S38-S42.

  5. Mydlo JH, Volpe MA, Macchia RJ. Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil. Eur Urol. 2000;38(1):30-34.

  6. Mas M, Escrig P, Abreu P, et al. Effects of experimental renal failure on mating behavior, penile erection and nitric oxide levels in the corpora cavernosa. Int J Impot Res. 2002;14(suppl 3):S15. Abstract B5.5.

  7. Montorsi F, Guazzoni G, Strambi LF, et al. Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective randomized trial. J Urol. 1997;158(4):1408-1410.

  8. McMahon CG. High dose sildenafil citrate as a salvage therapy for erectile dysfunction. Int J Impot Res. 2002;14(suppl 3):S89. Abstract CP5.11.

  9. Heaton J, Adams MA. An open-label pilot clinical study assessing the safety and efficacy of coinjection of prostaglandin E1 and a nitric oxide donor in preventing drug-induced pain. Int J Impot Res. 2002;14(suppl 3): S18-S19. Abstract C1.5.

  10. Nehra A, Goldstein I, Pabby A, et al. Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J Urol. 1996;156(4):1320-1329.

  11. Aversa A, Isidori AM, De Martino MU, et al. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf). 2000;53(4):517-522.

  12. Carson CC. Inhibizone antibiotic impregnation reduces penile prosthesis infection: preliminary results. Int J Impot Res. 2002;14:533-534.

  13. Licht MR, Montague DK, Angermeier KW, et al. Cultures from genitourinary prostheses at reoperation: questioning the role of Staphylococcus epdermis in periprosthetic infection. J Urol. 1995;154(2 pt 1):387-390.

  14. Parsons CL, Stein PC, Dobke MK, et al. Diagnosis and therapy of subclinically infected prostheses. Surg Gynecol Obstet. 1993;177(5):504-506.

Culley C. Carson, MD, the moderator, is Professor and Chief, Division of Urology, University of North Carolina at Chapel Hill. He is Editor in Chief of Contemporary Urology and is a consultant for Pfizer, Lilly, and Bayer.
Irwin Goldstein, MD, is Professor, and Director, Institute for Sexual Medicine and Director, Center for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, Mass. He is a consultant for Pfizer, Bayer, Lilly, Mentor, AMS, Wyeth, and Macrochem.
Ajay Nehra, MD, is Consultant, Mayo Clinic, and Professor of Urology, Mayo Medical School, Rochester, Minn.
Raymond C. Rosen, PhD, is Professor, Department of Psychiatry and Medicine, and Director, Program in Human Sexuality, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, NJ. He is a consultant for Pfizer, Bayer, Lilly/ICOS, Paladin Labs, and GlaxoSmithKline.

Culley Carson, Irwin Goldstein, Raymond Rosen. ED: What to do when pharmacotherapy fails. Contemporary Urology May 2003;15:28-46.

The idea of poor vascularisation due to a lack of testosterone or rather androgens is nothing new.

It is surprising that it seems new to these doctors.

Doctor Tvedegaard and Dr Jens Moller in Denmark used testosterone to treat arterial disease, particularly in the legs, they even used testosterone it to combat gangrene. So successful was this that they managed to reverse the effects of gangrene in patients treated with testosterone and saved many a limb. (Note: This is no different to the reversible effects noted in this article in the penis, it is the basic improvement of arterial blood flow and improved vascularisation). In 1957 this work came to the attention of the Danish health service and they sent in the state police because testosterone was not regarded as a medicine. This rapidly escalated into public hearings and a court case and questions were asked in the Danish parliament.

This whole episode was finally resolved when after two years, a minister of Justice who was on the state medical ethics committee and had a close relative helped by Dr Moller’s treatment got the case called off.

Dr Jens Moller was dealing with vascular changes due to Androgens after Dr Tvedegaard from 1977 to 1987 with Dr Malcolm Carruthers.

All of the above is explained in greater details Malcolm’s first book The Testosterone Revolution.

Back then the vascular issues of testosterone were concerned with the heart, arterial disease etc but its vascular effects throughout the body became widely known back then.

There was an entire chapter of the effects of blood flow on the penis in Dr Eugene Shippens book the Testosterone Syndrome, that was written many years ago.

So what these doctors are referring to, in terms of androgens affecting blood flow to the penis, causing changes in blood flow in the penis and in the effects a lack of androgens has on the penis;

It is nothing remotely new to the medical world, even if it does seem new to them.

In fact if they think this is something new then they must have been living on the dark side of the moon!

Furthermore in this article the doctors ideas of what is new in this area is nothing short of antiquated.

They mention “New concepts in androgen deficiency”.

NEW!!! is this some sort of joke?

New indeed if you mean known for well over 20 years in medical terms and new in a more general sense if you mean that antiquity has shown the effect of androgens on the castrate for over a thousand years!!!

Seriously is this some paper from the 1970s? If not don’t these doctors read much ? LOL for god sake.

They talk about problems being fixed by normalizing Androgens.

Sure I see so correcting erectile dysfnction in cases of hypogonadism is a simple case of normalizing androgens is it?

This again is the kind of language one would expect from articles written in the 1970s or from idiot endocrinologists who specialise in diabetes who last updated their knowledge of androgen issues back in the 1970s when they went through med school.

They know about a half of what they are talking about and that is outdated.

I think they should steer clear of all matters relating to androgens unless they are willing to pick their collective asses up and go and study and understand what has happened in the last twenty years in this field!

Dear me….

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Hypo, from my understanding what they were trying to say more importantly was that the tissue, callagenous tissue, tissue that was once thought damaged, can actually be repaired and it is NOT damged for good. I think that was more the thesis of their discussion rather than what you stated and what everybody already knows like you said.

First of all;

Did you read what I wrote about damaged tissue due to poor vascularisation as found in arterial disease and the impact that occured when treating such conditions with testosterone, the fact that damaged tissue was spared- limbs saved?

The cause is one and the same.

Damage die to poor vascularisation as a result of low androgen status is nothing new.

Secondly my points raised as to the outdated nature of the discussions are perfectly relevant.

I’ve said what I have to say so I’ll leave it there.

I have shrinkage due to finasteride myself. I was curious if anyone has actually been able to reverse shrinkage by increasing androgen levels and if so what androgen did they use?

Thank you


Has anybody made experience with this? I would visit Dr. Goldstein if he can reverse my shrinkage.