Sexual Concerns in Men after Transplant

Sexual difficulties, such as erectile dysfunction, are often experienced by men after a stem cell transplant. A number of factors can contribute to sexual problems, both medical and psychological. Both can be addressed to improve sexual health.

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Sexual Concerns in Men after Transplant

Tuesday, May 3, 2023

Presenter: R. Caleb Kovell MD, University of Pennsylvania School of Medicine

Presentation is 44 minutes long with 4 minutes of Q & A

Summary: Sexual problems in men after a stem cell transplant is quite common. This presentation reviews various types of sexual dysfunction in transplant recipients and available remedies. Patients are encouraged to learn about these issues and not hesitate to seek help when needed.

Highlights:

  • Sexual dysfunction is most likely to occur within one year post-transplant. Some men experience significant improvement within three years,  but without treatment, symptoms may persist longer for other men.
  • Medical treatments for erectile dysfunction include oral agents, mechanical devices, injectable agents, and surgery to implant a penile prosthesis. Each treatment carries its own risks and benefits which patients should carefully consider.
  • Low testosterone can contribute to sexual dysfunction, especially in men who have received radiation treatments and chemotherapy. It also brings other medical risks but there can be significant benefits from testosterone replacement therapy.

Key Points:

(02:45): Sexual problems in men can take a wide variety of forms beyond erectile dysfunction.

(06:25): Survivors of childhood cancer have a high incidence of sexual dysfunction compared to the general population.

(11:01): Graft-versus-host-disease significantly increases the likelihood of erectile dysfunction.

(11:14): Many different physical factors can impede achieving a successful erection.

(14:08): There are barriers to care on both the patient and provider side that include embarrassment and lack of familiarity with available treatment options.

(15:16): There are a variety of oral medications for erectile dysfunctions that each work somewhat differently.

(26:57): Nutraceutical treatments are not regulated or consistent in dosing, and there’s very little evidence that they help.

(28:15): Low intensity shockwave therapy may improve erectile dysfunction but not completely solve the problem. It can also be expensive and may not be covered by insurance.

(38:06): Several factors may also contribute to orgasmic dysfunction in men.

(42:01): Transplant patients should  be aware of the risks of sexual dysfunction, but also know that these problems sometime improve with time and that medical and psychological help is available. 

Transcript of Presentation:

(Note: In this presentation, when the speaker uses the term bone marrow transplants, it includes stem cell and cord blood transplants as well.)

(00:01): [Steve Bauer]:  Introduction. Hello and welcome to the workshop, Sexual Concerns in Men after Transplantation. My name is Steve Bauer, and I will be your moderator for this workshop.

(00:11): It's my pleasure today to introduce the speaker, Dr. Caleb Kovell. Dr. Kovell serves on the urology faculty at the University of Pennsylvania's Perelman School of Medicine and the Children's Hospital of Philadelphia. He is the director of genitourinary reconstruction transitional urology, and Program Director for the Urology Residency Program at the University of Pennsylvania Hospital. A large part of his practice focuses on helping men with sexual health issues such as erectile dysfunction in the post-transplant or cancer survivorship setting. Please join me in welcoming Dr. Kovell.

(01:05): [Dr. R. Caleb Kovell]:  Overview of Talk. Hi everyone. Thank you so much for having me today. It's a pleasure to be here talking to so many people. Today we're going to be talking about what I think is, a really important issue in the post-transplant survivorship patient population. Something that I think a lot of people are a little either less familiar with, or perhaps a little less comfortable discussing.

(01:23): My goal today is to try to go over many of the basics of sexual health concerns in men, especially after transplantation. I'll talk about some of the diagnostics we use, some of the options we use in terms of management and some of the reasons we go about that. I'm going to try to speak for about 40 to 45 minutes and then leave the time open for questions. Hopefully we can get to as many questions as possible and have a good robust discussion afterwards.

  We'll go over some of the slides about when that occurs. Over the course of post-transplant life, about 50% of patients will experience some impairment in their erectile function, their sexual function after transplantation. Now, this can be early in the early parts of transplantation and therapy. It could be delayed up to years afterwards, and there could be, potentially, many reasons for that. Or it could be prolonged and kind of waxing and waning in between.

(02:19): Symptoms of sexual dysfunction may resolve in many individuals over time but for others, they may persist for months, years, or even longer throughout a lifetime. The positive thing about this is that help is often available if it is sought out. This can have a substantial effect on the quality of life of individuals who experience this. A partnership with a physician who does work in this area and is willing and able to treat you, and help you out with this, could be extremely beneficial.

(02:45): Sexual problems in men can take a wide variety of forms beyond erectile dysfunction. Sexual health is much more than erectile dysfunction. For us men, oftentimes when we think sex, we think erections. While that is true, and while erections are often a big part of sexual response, they're certainly not all that comes with that. Beyond erectile dysfunction, many individuals can have issues with ejaculation, whether it be delayed ejaculation, retrograde or anejaculation where less fluid comes out, or premature ejaculation where they get to ejaculation sooner than they would generally desire. There are also potentially issues with orgasm function or orgasmic dysfunction where a man can struggle to get to orgasm or have pain or dysfunction associated with either orgasm or even prolonged after they experience orgasm.

(03:32): For some individuals, climax urea, or leakage of urine during orgasm, can occur. For many others, they'll have issues with things like libido, testosterone issues, loss of penile length or girth, fertility concerns, or things like penile peyronie's disease, which essentially can involve penile curvature or penile wasting, that can be highly associated with erectile dysfunction, and length and girth loss. You may experience any of these or all of these at some point after transplant, and we'll try to get into some of the big ones of these today. Just know that not all sexual dysfunction is erectile dysfunction.

(04:08): There are several potential causes of sexual dysfunction after transplant including radiation, chemotherapy, and psychogenic factors.  So I want to go over some potential causes of these. There are many reasons why a man may have issues with erection or sexual health. The first three are probably the most important, or at least the most common, in the transplant plant population. All of these things could apply.

(04:23): Certainly many, many survivors will experience radiation and chemotherapy. We know that these can have a direct effect on the erectile tissue, including the blood flow in the corpora cavernosa. They also can affect the overall nerve supply to the area, so they can hit many different areas that can affect erection.

(04:41): Psychogenic factors are also very important, and when I say that I mean things involving the mind and other kinds of stress factors that could contribute to this.

(04:50): Most cases of erectile dysfunction have a medical cause, although psychogenic factors remain important as well. Now, we know most people after transplant, and most people in general who have erectile dysfunction, have an organic or a medical cause that drives this, about 90% to 95%. In almost all of these individuals, psychogenic factors can still be important. Whenever an individual is stressed, when they're concerned, when they're worried, when they're thinking about other things, this can certainly play a role in their libido, their erections, and ultimately their sexual response. I like to think that these things go hand in hand. To manage this, we often need to manage both the physical and the psychogenic factors.

(05:21): Various medical conditions or surgeries can contribute to erectile dysfunction. Now, outside of radiation, and chemotherapy, many other things can also contribute. Different medical conditions, like vascular heart disease or nerve issues, medications that we use to treat depression or high blood pressure, that can have side effects that can be an issue with erections or sexual response.

(05:39): Surgeries that some individuals may have, including pelvic surgeries like prostate surgery, prostate cancer surgery, surgeries for enlarged prostate, colon surgeries, vascular surgeries. All of these can potentially contribute by their effects on the supply to the nerves and the blood vessels, as well as endocrinologic or hormone issues. Things like testosterone and different other hormones that we'll get to throughout the course of this talk.

(06:04): I wanted to briefly review some of the literature as it relates to survivors of transplant. We won't go deeply into the weeds in any of these studies, but just so we've gone over it. The first is a Swedish registry study of over 2,500 survivors of childhood cancers between the ages of 19 and 40. This includes a broad swath of different types of cancers and management.

(06:25): Survivors of childhood cancer have a high incidence of sexual dysfunction compared to the general population. What we know from this study is that survivors of childhood cancer have a high degree of sexual dysfunction compared to the population that has not gone through childhood cancers. In male survivors, about 35% over the course of their lifetime, especially at this young age, report some degree of sexual dysfunction, and this can be even higher in female survivors. So, about a two-time increased risk in erectile dysfunction occurs as well as about twice the risk of orgasmic dysfunction occurs in these men compared to the general population. Certainly, a heightened risk.

(06:59): In another study, they also reported that after transplant, about 50% of patients reported that they had no discussion with their healthcare provider about sexual health issues. And given how common this is, this is a little concerning because this is an issue that is important for many individuals and their partners.

(07:14): Depression may significantly correlate with erectile function and sexual health three years after transplant. It’s a little bit difficult to know what is the chicken and what is the egg here, if it's depression that's driving part of the issues with sexual health or whether some of the sexual health issues are playing into depression, or if this is correlated with overall health and how people are doing. Clearly, people are upset and often depressed whenever they have issues with sexual health.

(07:40): For men, problems of sexual dysfunction are most likely to occur within one year posttransplant but can also improve significantly within three years post-transplant. For men, some of the big issues that people have is a decreased libido, a lack of interest in issues with erections. At year one, some of the big things that men focus on is concerns about their attractiveness, their appearance, their overall sexual prowess, as well as their erectile function, their ejaculatory function, and their orgasmic function. After three years, they found that many of the things involving erections, ejaculation, orgasms improved significantly, but they still had issues concerning their attractiveness and their fitness, things that worsen their sexual health.

(08:11): For women, there were similar concerns. We won't go over all of them here, but again, they were concerned about attractiveness, vaginal lubrication, painful intercourse, and orgasmic function. For anyone having a partner dealing with this on the female side, this can certainly be something that affects both men and women.

(08:27): I wanted to also highlight this study about androgens and different hormone levels in patients after transplant. Now, you don't have to understand all of the details of these graphs, but I thought that they do make it clear that if you look at the far-left lines on the left, those bars that are the dark lines are pre-transplant. The ones in the middle are one month after transplant, and the white lines are one year after transplant. You can see in the domains of things like erectile function, sexual desire, depression, almost everyone after transplant at one month goes down on those numbers. And then fortunately, many individuals respond and get back at least close to their baseline by about the one-year mark.

(09:04): Now this is the general population. This is certainly not everyone. Again, similar graphs when looking at things like orgasmic function, intercourse satisfaction, and overall satisfaction, as well as IIEF, which is a surrogate marker of erectile function. Again, fortunately many individuals do respond by one year, but certainly in that first initial period there's a big hit to all of these.

(09:26): Male hormones often drop within a month posttransplant but often recover within a year. In this study, they also found that different hormones such as testosterone and dihydrotestosterone were associated with recovery at one month, whereas a number of other hormones that can me be measured we're also predictive of recovery that comes one year later. It's not important to know the hormones and the changes, but just understand that the graph shows a significant drop for all of these domains within about a month, and then oftentimes a recovery in about a year.

(09:51): Sexual dysfunction negatively affects overall quality of life while improvement in sexual dysfunction improves overall quality of life. This was a meta-analysis of 14 different studies, essentially trying to combine the data from a bunch of disparate studies that are heterogeneous, have different populations in the transplant population, that use multiple tools in multiple time periods. One of the advantages of these is that in trying to put together smaller studies to get to bigger number, you can get to a better understanding. In looking at all these studies together, they found that sexual dysfunction negatively impacts the quality of life. The most common thing we see in men is erectile dysfunction, which we're going to spend some time talking about today. We find that if you have overall improvement over time in physical, psychological, and sexual function, this also leads to improved overall quality of life. Certainly, something that is helping to drive this.

(10:35): Finally, one last study to bring to everyone's attention here in an observational single center study of 105 consecutive subjects. They looked at different men and comparing them to the general population, found that in the year after transplant, there were much higher rates of erectile dysfunction, about a 72% increased risk, a higher risk of what we call hypogonadism or low testosterone, about a 21% risk, and decreased sperm production in almost 90% of patients.

(11:01): Graft-versus-host-disease significantly increases the likelihood of erectile dysfunction. Now, if someone does develop graft-versus-host disease, that also increases the risk even over the general bone marrow population at about a six times rate of developing erectile function. Certainly, something to be aware of.

(11:14): Many different physical factors can impede achieving a successful erection. Let's delve for a little bit into the idea of erectile function, because I think that's probably the most common thing we see in the post-transplant population. Briefly, just to review the physiology of erections, a lot has to go right for erections, which means almost any interruption to this can cause erectile dysfunction.

(11:32): Initially, patients need nerve stimulation. They need to be excited, they need to have the proper nerve channels intact, which we already said could be damaged or altered from things like chemotherapy or radiation. This drives a relaxation of smooth muscles.

(11:45):  So, so our blood vessels have smooth muscles in them, and when they relax, they bring more blood into the penis. The cavernosal arteries to the penis bring the blood into the paired corpora cavernosa, which you can see in the bottom left diagram here. This fills with blood, increases with pressure, and then the blood gets trapped inside by compressing the veins on the outside on the right picture, between the tough layer of the corpora on the outside. And during the sexual response, the blood stays in there to create a rigid erection.

(12:13): Other medical conditions can also contribute to erectile dysfunction. Now, beyond transplant issues, there are a lot of medical issues that can worsen this. For any patient that also has issues with things like diabetes, that in and of itself, even outside of transplant, gives a patient over a four-time relative risk over baseline of having issues with erection. Enlargement of the prostate, vascular issues, hypertension or high blood pressure, high lipids, all those things can increase one's risk of having issues with erections.

(12:38): The good part of this is there are often many efficacious and tolerable treatments that are available. We tend to think of the first line options and the second line options, the first line options being the more conservative.

(12:52): Sex therapy can help address psychogenic causes of erectile dysfunction. We talked about the idea that many patients have a psychogenic component to this. So for many individuals, sex therapy, relational counseling, working with someone who is specifically trained on working with these issues can be very important. When you look at the American Urologic Association guidelines, they essentially recommend that everyone who experiences sexual dysfunction also work with a counselor as well as a urologist on managing these different kinds of issues.

(13:20): Oral medications, mechanical devices, injectable agents and surgery can help with erection problems. Beyond that, we generally talk about oral medications, which I think probably everyone has at least heard of, or are familiar with, which we'll talk about today in terms of trying to help erections. For those who either are intolerant of or cannot use the medications, things like vacuum pumps, constrictive bands, and different mechanical devices are available.

(13:41): Injectable agents or we then talk about second line therapies, injectable agents such as different suppositories or injections into the corpora, or penal prosthesis surgery where we can put a device on the inside essentially to replace erections.

(13:54): We'll also touch a little bit on the idea of low intensity shockwave therapy, as this has been a common question recently, and has become something that's become a little more popular in both the press and in different areas of the country for of treatment of erectile function.

(14:08): There are barriers to care on both the patient and provider side that include embarrassment and lack of familiarity with available options. Before we get into the different treatments, let's talk a little about the barriers to care. Not surprisingly, patients with erectile dysfunction oftentimes face many barriers in getting the care they need. One of the primary things that we see is embarrassment. Many individuals are just too afraid, too embarrassed to seek out care or to talk about sexual health issues with their providers.

(14:29): There's also a lack of knowledge about normal function or the assumption that any of these treatments the patients go through are supposed to knock out their sexual function, and that they're not supposed to return to a good sexual life.

(14:41): There's also often a lack of familiarity with the fact that there are good options available for treatment. And, potentially, there could be for some individual cultural or religious beliefs that prevent people from seeking care.

(14:50): It's not just on the patient side. It's often on the provider side as well. Many providers lack the comfort or the knowledge to address sexual health issues in their patients. Unfortunately, still, in many countries, especially here in the United States, there are often lapses in insurance coverage for these kinds of therapies. Many insurers, even if this is related to transplant or cancer-related care, won't necessarily pay for some of these therapies. It does create another barrier in getting the right care.

(15:16): There are a variety of oral medications for erectile dysfunctions that each work somewhat differently. So, let's start out with the oral medications, what we call the PD 5 inhibitors. I put the names of them up there. I tried to put both the generic names and the trade names, which I think people are probably a little more familiar with.

(15:27): These are Viagra® (Sildenafil), Levitra® (Vardenafil), Cialis (Tadalafil), and Stendra® (Avalafil). These started in the late 1990s and have been growing in popularity until today. The nice thing about these medications, in most populations, they're relatively safe, with a few conditions, and usually pretty well tolerated.

(15:44): You can titrate the dose up or down. I usually start my patients on a high dose and then bring the dose down if they're having side effects, because I do think there is also a psychogenic component to this, in terms of seeing how these work and how these affect people.

(15:58): They all have pretty similar efficacies. They do have differences in terms of how quickly they come on and for how long they last. Some of the medications, like Avalafil, only take about 15 to 30 minutes for most people to come on, but go away more quickly, whereas Cialis® takes somewhere between two and four hours for onset, but then will last for anywhere from about 17 and a half to 24 hours in most patients. Depending on patient preferences, different medications can be used.

(16:23): There is also a difference in absorption with food. Some of the medications, like Viagra® and Levitra®, do require individuals to take them on an empty stomach to get the best results, whereas other medications, like Cialis® (Tadalafil), are a little bit less affected by food.

(16:36): Cialis® (Tadalafil) also can be used on a daily dosing so that it can build up to a steadier level for some people in their system, whereas all of the medications can be used on an "add as needed" dosing for someone who doesn't want to take the medication as much.

(16:50): Fortunately, even over the last few years, many of these medications have become much more cost effective now that there is generic dosing in different pharmacies available. What used to be very cost prohibitive now is often a little more manageable.

(17:03): Men with cardiac issues or retinal disease may not be good candidates for oral remedies to treat erectile dysfunction. Not everyone is a great candidate for phosphodiesterase (PD 5) inhibitors. Anyone with a significant cardiac history, so someone who's had a recent heart attack, especially within the last six months; any chest pain with exertion; strokes; heart failure; or significant heart disease will need to discuss taking these with their cardiologist and potentially have further workup before starting any of these medications, or frankly, before even getting back to sexual activity due to the potential risk.

(17:29): There is also a potential risk in patients with retinal disease, like retinitis pigmentosa, because some of these also have crossover with some of the different enzymes in the eye. They can also potentiate the effects of different medications for patients who have HIV and are taking HIV medication. For some of these, you really need to check with your provider to make sure they're okay. They can also interact with some pulmonary hypertension medications, as some of these do drop the blood pressure within the lungs. It does need to be discussed with other providers before starting some of these medications.

(18:02): Side effects [from oral medications for erectile dysfunction] are usually relatively mild, although for some individuals they can be more serious or intolerable. The most common things we see are headaches, flushing or facial flushing, because these medications were designed to increase blood flow; GI upset; and a drop in blood pressure.

(18:20): For some, especially Cialis®, you can see things like muscle aches or cramps, especially in the thighs or the butt, and there could be vision changes. For things like Viagra® or Levitra® sometimes people will have blue green color changes, especially in their peripheral vision. As far as we know, all these things do seem to get better when you stop the medication.

(18:38): Now, when we talk about priapism or a sustained painful erection that lasts for a long time and doesn't go away, that would actually be extremely rare with these medications. Many of us think that they often advertise this, mostly for advertising purposes to tell people that they're going to get a very prolonged erection, but it would be extremely rare that this would happen. Outside of the use of other stimulants, things like cocaine or uppers, usually if you don't pair these medications with anything else that's going to stimulate these effects, the risk is very low for them.

(19:09): These medications can decrease blood pressure. You should never take these within a short period of time of nitrates. If you are taking nitroglycerin, these are not good medications to use. If you're using alpha blockers, things like Flomax® (Tamsulosin) or Rapaflo® (silodosin) for prostate issues, these medications can drop your blood pressure so often you'll need to use them with care and spread them out over time.

(19:32): Vacuum erection devices and constrictive bands have some advantages for treating erectile dysfunction. Going on to some of the other therapies, we do talk about things like the vacuum erection device. Here on this page is a picture of the vacuum devices and bands. You put the device over top of the penis. Nowadays you usually press a button, although they still do make ones with hand cranks or pumps, and the whole idea is for the vacuum to draw blood into the penis. Now, this is primarily venous blood, which is different than a normal erection where you get the kind of warmer, firmer arterial blood. Many individuals will note that their erections are a little softer and a little colder with this.

(20:03): To hold the blood in, often you need to wear a constrictive band or a ring around the base of the penis. They should not be overly tight and should never be metal so that if it ever needed to be cut off or you couldn't get it off, that would be able to happen with your healthcare provider.

(20:17): The advantages are they're spontaneous, almost every man can get an erection with it if they use it. They're relatively cheap and most insurance companies will pay for at least part of them. Once you buy them, you don't have to buy them over and over like some of the other medications. Some of the disadvantages are they can cause bruising, especially for patients on blood thinners, and you do have to wear a band which can be uncomfortable for some individuals.

(20:40): Next we'll talk about the second line therapies. So, when those more conservative therapies don't work as well, then we start getting into some of the other therapies that are a little more tried and true and a little more potent.

(20:51): Second line therapies for erectile dysfunction include intra urethral suppositories. The first one is what we call intra urethral suppositories or MUSE. That's the medical-use suppositories for erections. This comes in an applicator, as you can see on the screen here. You put a little bit of lube on it, hold the penis up straight, and it goes in through the tip or the urethra, and then you press the button on top to deposit a pellet within the urethra. The individual then does a massage of the area, and usually if it's going to work, within about 15 to 30 minutes this will help diffuse over to the erectile tissue and create an erection.

(21:20): The advantages are relatively rapid onset compared to some of the oral medications, and it works for about half of men who are not able to use the oral medications. Some of the disadvantages are that many individuals are not particularly comfortable with the idea of putting a suppository in their own urethra. If they are, they sometimes will get some burning or some irritation of the urethra, especially with voiding, and you can have some blood, off and on, with this. It can be a little bit uncomfortable for many men. In the most recent years, especially since COVID, it has also been a little bit difficult to get this with supply issues. Sometimes they're available and sometimes we have had some difficulty getting it for individuals.

(21:57): Another treatment for erectile dysfunction is intracavernosal injections or ICI but they should be used with caution. The next therapy is what's called intracavernosal injections or ICI. This is sort of the next step up. This involves drawing up a small amount of medication to inject within the penis. This is obviously a more potent medication, and they make different mixes, some that are available at the pharmacy, some that require a compounding pharmacy to make and send out to your house. Now the nice thing is that it's a very small needle. The onset is very rapid, and it does create a very natural erection with the arterial inflow of blood as opposed to bringing in venous blood. It comes on quickly, usually within about 5 to 15 minutes, and it is better with stimulation, and it is quite effective. Many individuals who have failed other medications can have about a 70 to 90% success rate with these.

(22:38): The disadvantages are, obviously, the use of needle. So that does turn off a lot of individuals, especially before sexual activity. You do have to learn how to put it in and most providers will generally bring you back to their office to do the first injection with you and your partner, to make sure that you feel comfortable doing it and you're doing it the right way.

(22:56): You do have to start at low doses and slowly work your way up until you get to the right dose that works for you, because there is a real risk of priapism or prolonged erection with this. There's also a potential, or more of a theoretical risk, of scarring from sticking the needle into the corpora and putting medication there. It would be rare that anyone would get scarring that was bad enough to create more erection issues or to create curvature.

(23:17): Now, there are times where this is not quite as effective. You can't use it with MAOI inhibitors. For many years, almost no one was using these, but more recently for patients with depression and other issues, they have made somewhat of a comeback. If you are on any of these classes of medications, you do need to check with your provider. You also need to be careful in patients with severe blood pressure issues because the medications you're putting in do potentially change the blood pressure for some individuals.

(23:42): These can also be challenging in obese individuals because it can be difficult to see or visualize the phallus. Individuals with dexterity issues can have problems because they have to draw up the medication and learn how to put it in themselves, unless they have a partner. Ditto for vision issues. We use it with caution in anyone on blood thinners like Coumadin®(warfarin), apixaban, rolenta, any of those things. Doesn't mean you can't, it's a small needle, but again, there is a little higher risk of bleeding.

(24:08): A penile prosthesis is a surgical option to treat erectile dysfunction that is equivalent to an erection replacement.  The final solution that we'll often use for some gentlemen, if the other options are not as useful or aren't as tolerable, is what's called a penile prosthesis. This is a surgical procedure. I like to tell patients it is essentially the equivalent of an erection replacement, similar to a hip replacement or a knee replacement. The whole idea is putting a device on the inside of the corpora that creates a good firm rigid erection that can be used for masturbation or sexual activity. The patient can usually either pump it up any time that they want, and take down any time that they want. It does not affect things like sensation, orgasm, or ejaculation for most individuals. If those issues are good, they'll stay good. If they're not good, they unfortunately won't be helped by this device. It's been around for over 50 years now. It was first developed in 1972 and it's highly effective with high rates of satisfaction over 90% for both individuals and their sexual partners.

(25:01): These are just some pictures of the penile prosthesis. There are a number of different models. In the top left, you'll see what's called the malleable or semi malleable or semi rigid prosthesis, which is essentially rods that get fit directly into the corpora that an individual can bend up or bend down. These are a little bit less natural, but easier to use in the sense that you don't have to pump anything up and you don't have to have as much dexterity in order to use them.

(25:23): There are also inflatable penile prosthesis, the most common of which is at the bottom here called the three piece device, which has a set of cylinders that go on the inside of the penis, a pump that goes down and is hidden under the skin and the scrotum, and a reservoir that gets put back behind the pelvic bone so that saline can basically go between the different parts of the system from the cylinders into the reservoir and back, when the patient wishes to have a rigid erection and when the patient wishes to have a flaccid phallus.

(25:51): Just like anything else, there are risks to these procedures. Fortunately, nowadays, the risk of infection for most individuals is less than 1%. This has been a big boon over the years, that now these are much safer procedures. They're all coated with antibiotics, as you can see in these bottom two pictures where one is yellow, and one has been dipped in a bluish solution. Now, there is a slightly increased risk, for sure in patients who are on immunosuppression, patients with diabetes, patients with healing risk. That does have to be discussed with your provider.

(26:19): There is a risk for malfunction or a need for replacement over time. On average these last somewhere between seven to 10 years. But there is a chance, just like a hip or a knee, that any device could wear out or break over time and require a surgical fix. And for a period of time, as you can imagine, there is some discomfort and recovery time, just because it's a very sensitive area that your body has to get used to.

(26:40): The positive thing is once these are in and once you heal, they're entirely hidden on the inside. If you were to walk around somewhere like a locker room, no one would know that you had it in. It's very personal, and again, guys generally do quite well with these and can use them over time. It basically becomes a part of their body.

(26:57): Nutraceutical treatments are not regulated or consistent in dosing and there’s very little evidence that they help. Let's talk about some things that come up a lot - the idea of nutraceuticals. These are the things that you might buy at a men's health store, things like a GNC or a vitamin store. In the United States, this has really become a multi-billion dollar a year industry. Now we can argue how helpful these are, but what we do know is that there's no regulation of any of the ingredients in them. The dosages they're reporting are not necessarily accurate. For many of these, even if the bottle doesn't list it, they may contain traces of things like testosterone or testosterone additives or other medications like Viagra® , Cialis®  - the PD5 inhibitors that have to be used with care. Especially if any of those medications may cause issues for you, definitely be careful and know that these are "buyer beware".

(27:43): Always remember, too, that there's a 30% placebo response rate for erectile dysfunction medications. Part of the question is, if you're spending a lot of money on these, is it really the medication that's working or is it a placebo kind of effect that's helping?

(27:56): I just listed over here several different compounds that we tend to see in these. things like Korean Red Ginseng tends to be a common one, Fenugreek, L-Arginine, Maca, lots of different things are common men's supplements. The jury is out, given that there's very little evidence that these really help, so buyer beware.

(28:15): Low intensity shockwave therapy may improve erectile dysfunction but not completely solve the problem. It can also be expensive and may not be covered by insurance. The other thing to bring up quickly is the idea of low intensity shockwave therapy. This has not been approved or made it into the guidelines, but we are seeing more and more men consider this option.

(28:25): The whole idea is to use shockwave therapies, which we've traditionally used for things like kidney stones or breaking up pancreatic stones, to try to create a microtrauma within the penis and allow for the creation of new blood vessel formation, stimulation of different cells like Schwann cells or bringing nerves back. No one exactly knows quite how this would work, but these are some of the proposed mechanisms. The whole idea is that you come into a provider's office, they basically can numb the area up and use shockwaves at low intensity to try to regain erection.

(29:00): Now there have been a number of studies on this over time. I thought this was one of the better ones to bring up where they actually randomized patients, 70 patients with moderate levels of erectile dysfunction, to 12 different sessions over a six-week period of either low intensity shockwave therapy versus a sham treatment.

(29:17): You don't have to worry about the impulses they used, but again, this is not standardized. They showed that about 80% of men reach criteria for some level of improvement versus 0% in those who got the sham treatment. Now, the IIEF score differed by about four points in each. What that means is that many of these men still went from moderate erectile dysfunction to still having either moderate or mild to moderate erectile dysfunction. So, while they did show an improvement, part of the question is always, clinically, was this enough to make it worthwhile?

(29:47): Now, right now we have no data for this in the post-transplant population, and we're not sure, the jury is still out how much this may be helpful for men. But there seems to be relatively little side effects other than the fact that usually treatments are somewhere between $3,000 and $5,000. They can be quite expensive. They're not generally covered by insurance. Again, buyer beware.

(30:07): Low testosterone can also be an issue in sexual dysfunction and especially with men who have received radiation treatments and chemotherapy. Let's shift a little bit here. Going from erectile dysfunction to what we call hypogonadism or low testosterone, just because this is another thing we often see in patients after transplant. The same things that tend to cause issues with sexual health with erectile function also are the things that can potentially potentiate or worsen things like testosterone issues. Chemotherapy, radiation exposure, especially to the nerves and to the testicles can cause this.

(30:31): We know that about 90% of the testosterone in a man's body is from the testicles and the Leydig cells, and the other 10% is from the adrenals. For those patients who get full body radiation, especially to the testicles, this certainly is a potential concern, and you should know that this can be an issue. We also see this in patients with chronic opioid use or narcotic usage, chronic steroid usage, pituitary issues, HIV or diabetes. Lots of reasons why this could happen.

(31:01): We also know that not all issues with things like libido are related to testosterone. If you were to listen to the radio, you would think that almost every man has low testosterone and would benefit from testosterone therapy. We know that that is very likely not true. While some libido issues definitely come from decreased testosterone, we can also see other hormones having an impact here. Increased prolactin level or decreased thyroid hormone levels can also be an issue. Some individuals will check things like TSH, and we also can see this in vitamin and vitamin processing. Things like B12 levels, Vitamin D especially in the wintertime, could potentially have an impact on libido, energy, and ultimately sexual response.

(31:41): Other medications and psychogenic causes can also reduce libido in addition to low testosterone. Many medications can also play a role in this, so things like antidepressants, SSRIs, SNRIs. So while things, like Wellbutrin, may be a little more friendly than some of the other medications in terms of sexual response, it's always worth talking to your provider, whether it be your counselor, your GP, whomever it is for some of the medications like antidepressants, antihypertensives, because many of those can have effects, and there may be other options or lower doses available.

(32:07): And then we always come back to this idea of psychogenic causes. So, stresses in your life, difficulty with dealing with things like cancer, survivorship, that of your family, your partner, financial issues, all of those things we know definitely play a role in libido and sexual response.

(32:23): So, when it comes specifically to low testosterone, what are some of the signs and symptoms? Decreased libido, decreased sexual desire. One of the big things we know is that as testosterone levels decrease, this usually worsens well before things like erections do. As guys get into the level of about 300 to 500 of their testosterone, usually the first thing that goes is their libido. Their energy can be off. Later on, as we get to lower levels, like the 300s to 200s or 100s is when we start to see a true response in terms of erections for most men You can also see decreased muscle mass, loss of bone density, with that weight gain and increased fat distribution across the body, depression, irritability, and decreased productivity.

(33:05): Testosterone levels decrease with age and vary throughout the day so care is needed in assessing if it is contributing to sexual dysfunction. There's a lot of overlap with other conditions, especially someone who's undergoing cancer treatment, radiation, chemotherapy. Not all is from testosterone, but it's certainly a worthwhile discussion to have with your provider. One thing to know is that testosterone levels do decrease naturally over time. Once we men get into our late twenties, early thirties, if you track testosterone levels over the course of your lifetime, they will continue to fall over time. That's relatively natural. There's nothing that says when you're in your seventies or eighties you need to have the same levels as what you do in your thirties, but you can still see more severe dips in some men.

(33:38): These levels can also be highly variable throughout the day. There is what's called a diurnal variation testosterone, where it tends to be high in the mornings and high sometime in the afternoon or evening, and you have peaks and valleys throughout the day. There's no particular reference range for an individual. What might be right for you may be different for someone else. Again, just because you're at a certain number, without symptoms or with symptoms, your provider may work with you to determine whether you need supplementation or not.

(34:03): When we check testosterone levels, we usually check it early in the morning, around 8:00 AM just because the reference rates are about the best for that time. If it is low, your provider will often repeat testing again with a more extensive panel. If it's low, then your provider will talk to you about should we do a trial with different forms of testosterone, or should we continue to watch this closely? So again, there are certainly some risks to having low testosterone.

(34:28): There are definite risks with low testosterone and significant benefits in maintaining normal testosterone levels. We always talk about the risks of treatments, but there are definitely risks to having low testosterone. Interestingly, for a while we thought that higher testosterone will lead to increased cardiovascular events, but we found that, in general, that doesn't seem to be the case except in very high-risk individuals. For individuals with low testosterone, there is a higher risk of cardiovascular events - heart attack, stroke, things like that. There's also a risk of lower bone mineral density and ultimately fractures, cognitive issues, troubles with diabetes and glucose control and nerve recovery.

(34:57): One of the other big thing to know, for some individuals, is that PSA production, which comes from your prostate, is lower when you have low testosterone. It's actually harder for your provider to watch you and screen you for prostate cancer issues if your PSA is low because your prostate is not making that marker as well. It can lead to later detection of things like prostate cancer.

(35:18): Another slide just to drive this home a little, this is a veteran study of I think, almost 900 men who had serum testosterone levels checked. You'll see that blue line is the overall survival, not just related to testosterone or erections or anything else, but the overall survival of all men with normal testosterone. The red line is those with equivocal or borderline testosterone, and the bottom one is men with low testosterone. You can see there clearly is a mortality difference in men with low testosterone. Now, there could be other reasons for that. Testosterone tends to correlate with different disease states and things. But even after age, medical comorbidities, and multiple other co-variables were accounted for, low testosterone individuals did have a higher mortality when their testosterone levels were low.

(36:08): There are many different options available for supplementing testosterone although there are risks as well. There are some risks to this for sure, just like with all the treatment options for erectile function, including increased hemoglobin levels. This does have to be watched and monitored by your provider. Breast enlargement, changes in the mood as well as changes potentially in prostate cancer risk for some susceptible individuals are possible. Many individuals will also note that they have a body rash or acne on their chest or their back. You also can get smaller or softer testicles. Some men are bothered by that for sure.

(36:37): The other thing definitively to be aware of is that you can get decreased sperm counts with this. Testosterone replacement therapy is being used, or being at least trialed, in some individuals as a male contraceptive. If you are thinking about fertility issues, testosterone in and of itself may not be the best choice, but there may be other options to stimulate your body to try to help with testosterone production in other ways.

(37:01): Testosterone replacement therapy can have multiple benefits and there are several routes of administration. Some of the benefits go along the lines of what we were just talking about before; better libido, better energy, cognition, glucose control, bone mineral density, and for some individuals there may be a decreased MI (myocardial infarction) risk or cardiovascular risk and a decreased mortality risk overall.

(37:16): There are multiple different routes of administration. Most commonly these are done through topical gels or creams. In some areas, there are patches available. Other individuals choose things like intramuscular injections, which are often done a weekly or every other week basis, and nasal sprays. Over the last few years, oral formulations have become available, although sometimes they're a little more limited.

(37:39): There are also longer acting formulations, most commonly in the form of subcutaneous or an under-the-skin pellet that can be put in in a doctor's office and lasts usually for about three to four months before having to come back for another installation. All of these do require symptom checks and monitoring. All of these do require lab work, including hemoglobin, lipids, liver function, PSA levels in susceptible individuals. It does require close monitoring with your provider.

(38:06): Several factors may also contribute to orgasmic dysfunction in men. Just to briefly touch on some of the other sexual response issues, things like orgasmic dysfunctions such as delayed orgasm, or anorgasmia. These are very common and associated with things like decreased testosterone. They can be very common in patients who are on SSRIs for depression, and we do use SSRIs for some individuals with premature ejaculation to try to prolong that. But again, if you were on those medications for something else, it is not uncommon to have issues with orgasm. Bringing that to the attention of your providers to work on dosing or potentially even tapering these off can be really important.

(38:42): We do know that things like psychogenic contributions, stimulation and genital sensation are some of the most important things with this. For individuals who have peripheral neuropathies with diabetes or from chemotherapy, or patients that have any spinal cord pathology, that can lead to nerve function, can lead to stimulation and sensation, and whenever you're feeling less or having less pleasurable intercourse or masturbation, it can lead to a more difficult time getting to orgasm. Again, psychogenic contributions can be really important here.

(39:13): Beyond decreased stimulation, if you're not excited, if your libido is not there, if you're not into what's going on, there certainly is an increased threshold to reach orgasm. Some things just to think about with that.

(39:24): Cancer treatments can also affect male fertility so sperm banking can be an important option. Just to bring up the idea of fertility issues, because certainly some patients posttransplant are interested in childbearing and fertility. Many of the treatments that are used for cancers can certainly affect sperm counts. These may be temporary. In general, the life cycle, in terms of production of a sperm, is about 72 days or so, so somewhere in the ballpark of about three months. All of these things, if they're simply knocking out the sperm, it can take at least three months to recover. For things like chemotherapy and radiation, they can affect the overall structure of the testicles, they can affect the brain in terms of pituitary access.

(40:01): For individuals who know that they're interested, sperm banking, cryo-preservation before transplant can be really important and you can work with your providers on this. We generally tell people to avoid pregnancy for at least a year post-transplant with optimal sperm recovery coming usually in the ballpark of two to five years after transplant.

(40:21): Semen may look very normal. It generally doesn't change, the same way that semen quality and quantity generally doesn't change after vasectomy. But it could have either diminished or damaged sperm. You just have to be careful around fertility issues after transplant for a period of time.

(40:38): Psychogenic issues in male sexual dysfunction are also really important and patients should not hesitate to seek appropriate care. Just to hit the point again, because I want to finish with this. The psychogenic issues, beyond all the medical issues, are really, really important. This is just from one study looking specifically at people after transplant issues using a model that they came up with for getting back to sexual health in terms of all the psychogenic and all the psychosocial issues related to this.

(41:00): For many individuals, after they go through transplant, after they go through cancer survivorship, they come to a period where they realize that this is an important part of life that they're missing. It doesn't mean you have to, but if you do, there are different stages of this identifying the importance of sexual relationships, taking responsibility in terms of deciding you're going to seek care and kind of move forward with your help on this, seeking resources and providers that can help you with this, and then ultimately navigating a partnered relationship, if that's something you're looking for.

They did find that it was somewhat gender specific. This may be different for male and female patients, cisgender males and transgender males, and there's often a non-linear progression where you can't just expect that day-by-day this is going to get better. Sometimes this goes in fits and starts, and it's very important to consider sex therapy, relational counseling, working with someone other than just a urologist, someone who really is trained in helping individuals through these things.

(42:01): Transplant patients should  be aware of the risks of sexual dysfunction, but also know that these problems sometime improve with time and that medical and psychological help is available.  Just some take home messages for patients undergoing transplant. We know that they are at risk for sexual dysfunction both early and late. We know that there are many different types of sexual dysfunction. It's not just all erectile dysfunction, many other things may be going on.

(42:13): Erectile dysfunction and decreased testosterone are some of the most common things, and we know that there are treatment options available that are quite effective for them. There's not always a one-size-fits-all model for this. Working with a provider to work on something that works for you can be very helpful.

(42:30): For many individuals, these issues will improve naturally over time, but not for all. And, really, don't take another person's story as what should happen for you. The last thing you want to do is be comparing yourself to what is happening for others, both on the good side and the negative side.

(42:44): Again, there are providers available to help. When you are ready and when it's needed, please reach out to someone who can help you navigate these waters. I'll stop there. Thank you so much for your attention. I hope this was helpful, and I'm going to open it up to any questions that you may have and for a discussion over the last 15 minutes or so.

Question and Answer Session

(43:04): [Steve Bauer]:  Thank you, Dr. Kovell, for this excellent presentation. We'll now begin the question and answer session. Our first question is, my sexual situation has a double hit. My wife has vaginal dryness and pain. The husband, the patient has ED. This double plumbing sex problem has not been addressed post CAR T. What resources are available for me?

(43:31): [Dr. R. Caleb Kovell]:  Yeah, that's a great question. It's also a very common thing. For many individuals, depending on where their partner is in terms of their life, their age range, their medical situation, it is very common for either female partners or male partners to have sexual health issues of their own. That often doesn't just make the situation tougher, it makes it exponentially more difficult.

(43:52): There are lots and lots of resources available online in different places, both for the transplant population, but also for men in general, in terms of erection options, and for providers who are available to help with this. For female partners, certainly the idea of working with either their gynecologist, their urogynecologist, or even their primary care provider on this can be really helpful. Similar to in men, how we talk about replacing testosterone, for many women, the option of things like vaginal estrogen can be really, really important, and doesn't carry nearly the risks that we tend to think of with estrogen on a more systemic level.

(44:28): It often is very safe for individuals, even who have had other issues like breast cancer or endometrial cancer. It obviously needs to be discussed with their provider and with an assessment as well.

(44:39): Then for some females, things like testosterone therapy in much lower doses or different medical options may be available to help them with either vaginal dryness, lubrication, excitement, libido issues, different things like that. So certainly reaching out to their medical provider can be very helpful.

(44:58): Then for couples, we talked about the idea of sex therapy or relational counseling. For some individuals, men will choose to do that on their own first. In terms of the relationship, bringing that together and both of you working together, can also be really important to have a counselor, a provider, a therapist, someone who works together. It's not because there's a problem with your relationship, not because you're crazy, but really because these things can be a big hit for men and their partners. Getting a full team available to help you through both the medical and the psychogenic sides can be really important.

(45:30): [Steve Bauer]:  Thank you. Next question is, what is the most important test, free T or total testosterone?

(45:39): [Dr. R. Caleb Kovell]:  Yeah, it's a great question. It is different for different individuals, and it may be variable for different people depending on where they are in their lives. How I usually do it for most individuals is going to be checking the total testosterone. If the total testosterone is well within range, for most individuals, I'm going to be hesitant to supplement them.

(46:04): For some individuals, however, free testosterone is basically the total testosterone minus the part of the testosterone that is bound to other enzymes, and then it's not available to use. For some individuals when their total testosterone is more borderline and their free testosterone is definitively low, supplementing their testosterone can definitely be helpful for them. It may be less helpful than when their total testosterone is clearly in the low range.

(46:30): With those individuals, I do talk to them about the idea of a more guarded trial, seeing how they are with their symptoms in three months, making sure they're responding, potentially using other agents. Usually both of those will be measured and we'll use them both. If you had to pick one, I generally, for most individuals, think the total T is more important and often the free T can give additional insights into testosterone issues as well.

(46:56): [Steve Bauer]:  Thank you. Next question I think was mostly addressed in the answer for the first question, but simply, what type of provider is best to start with?

(47:08): [Dr. R. Caleb Kovell]:  I think for most individuals, starting honestly with their primary care provider is a great way to start, or potentially for some, with their oncologist. You already have a relationship with them. They often know you well. For many things like Sildenafil, Tadalafil, the medications, referrals to therapists, many times they can help you out with that. If those are effective, you don't necessarily need to go and establish care with a urologist. Now, if you feel more comfortable talking to someone who's a sexual health expert, especially a urologist with insight into managing patients with sexual health concerns such as erectile dysfunction that can be very helpful.

(47:48): For females, sometimes a urogynecologist or a gynecologist can be helpful, but really the person you want is someone who feels comfortable managing sexual health issues and will help you reach your goals. That doesn't necessarily have to be a specific type of doctor, so start with your primary care doctor. But if needed, have a low threshold to reach out to your urologist to have some of these conversations as well.

(48:13): [Steve Bauer]:  Closing. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Kovell for a very helpful presentation. And thank you, the audience, for your excellent questions that were presented. Please contact BMT InfoNet if we can help you in any way.

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