Amazingly, some men are able to ejaculate and feel sexual pleasure with stimulation of the remaining parts of their genitals, and, if they have a part

Transcription

1 Hi, I'm Dr. Leslie Schover. I'm a Professor in the Department of Behavioral Science here at MD Anderson Cancer Center and I've spent a lot of my career working on research and clinical work trying to help patients with the reproductive issues they have related to their cancer. So today I'm going to be talking about sexual health after cancer. Why should sexual health be an important part of survivorship? Well sexual dysfunction happens to be one of the most persistent consequences of cancer treatment. And if you think about anxiety and depression related to a cancer diagnosis, in the great majority of people, those problems resolve by a year after cancer treatment if the patients don't have a recurrence. However, in contrast, sexual problems don't go away with time, unless you do something to treat them. They're also very common. In men sexual dysfunction affects perhaps 70 percent of prostate cancer survivors who have various types of treatment, at least half of men who have colorectal or bladder cancer, and about a third of men who have bone marrow transplants, just for some examples. And so if we think about the data on how many cancer survivors are currently in the United States, that means that at least 1.8 million men, with an additional 22,300 per year, are affected by sexual dysfunction that is not going away. The most common sexual problem we see in men is erectile dysfunction and we know that even when men don't have any major health problems like cancer that the older men get and the more they have cardiovascular risk factors, the more likely they are to actually have problems with erection as they age. After cancer treatment additional factors include damage sometimes to pelvic blood vessels, damage to the autonomic nerves involved in erection, abnormal hormone levels, and actual loss of some of the genital tissue. So I'm going to go over each of those in turn. When we think of the pelvic blood vessels, radiation therapy for a pelvic cancer with prostate cancer being the most common example, can cause a slow decline in the circulation of blood available to the penis after the end of radiation therapy. The extent of the damage depends on the size of the radiation field, of course, how close it is to the penis and its blood vessels, the ability to focus very narrowly on the tumor, for example, with the use of brachytherapy or photon therapy or computer-guided imaging, and also the intensity of the therapy. And in terms of when you see this problem, it often doesn't start immediately at the end of radiation therapy, but a man may notice a gradual decline in his erections beginning a few months later and we know that that decline continues for at least three years afterwards and probably continues beyond that. Of course, you have to separate out the aging from the radiation therapy effects. Autonomic nerves in the pelvis are damaged during radical surgery with radical prostatectomy, again, being the most common example. But when you have radical cystectomy for bladder cancer, you not only remove the bladder but also the prostate. So the nerves that run close to the prostate often get damaged and also abdominal perineal resection for cancer low in the colon, or in the rectum, also often damages those nerves and surgeons have tried to modify surgery to spare the prostatic nerve plexus which is the important one that directs blood into the penis. So, it's not the nerves that help a man feel sensation of pleasure when his penis is touched, but these are the nerves that direct blood flow into the penis. Another problem that can happen from nerve damage in this area or a little higher up, is that man may experience the pleasure of orgasm and even have muscle contractions around the base of the penis that normally occur during orgasm, but no semen comes out because the autonomic nerves that control the prostate in seminal vesicles, the body's semen factory, actually are damaged and those organs are essentially paralyzed. Now, hormone therapies are --- hormone abnormalities, I'm sorry, are less common side effects of cancer treatment but they do occur in some cases, and again, the most common hormonal abnormalities we see are when men are given hormone therapy for advanced prostate cancer and the goal is to get their circulating testosterone down as close to zero as possible and sometimes also to block testosterone from entering its target cells. So, the common picture that you see is men lose interest in sex, and along with that, may have difficulty getting or keeping erections or reaching an orgasm because they don't feel the pleasure of sexual stimulation as strongly. Another group of men who may have hormone abnormalities are those who have quite intensive chemotherapy. For example, in preparation for a stem cell or bone marrow transplant, and in those men when they develop sexual problems it's helpful to look at a hormonal profile and make sure that low testosterone is not the problem. Nowadays we have ways to replace testosterone with patches or gels that gives steady levels of replacement and that certainly is very helpful to men who don't have prostate cancer. There is some controversy about whether some men with prostate cancer can actually take hormonal replacement and research is going on in that area. Now, unfortunately, some cancers involve actually removing part of the genital area. Penile cancer is a rare cancer in the U.S with fewer than 500 cases of invasive penile cancer a year, but when it does occur, it can be very deadly and either part or all of the penis needs to be amputated surgically to halt the spread of the cancer if it's still localized.

2 Amazingly, some men are able to ejaculate and feel sexual pleasure with stimulation of the remaining parts of their genitals, and, if they have a partial penectomy they often get enough of an erection to actually have intercourse with the partner. Unilateral or bilateral orchiectomy are surgeries that are done, bilateral orchiectomy most commonly as a type of hormone therapy for prostate cancer. When men have testes cancer, it's rare that they have both testicles affected, but they often have one testicle removed and some have actually silicone implants put in to hide the cosmetic effect when they are in the locker room or with the sexual partner. Some men also have to have a pelvic exenteration that involves removal of the bladder, the rectum, the prostate and creation either of a urinary ostomy and a colostomy, or now creation of a neobladder or reconnection of the intestines. So that's quite a major surgery and very often is going to leave men with erection problems. And so in a way, this is a horrible live laboratory that helps demonstrate that the various parts of the male sexual response are independent, that you can have pleasure with touch, and even reach an orgasm without having an erection. You can have orgasmic pleasure without ejaculating semen, and you can have all of that happen with the soft penis and men often don't know that. So when they have an erection problem, they don't try to see if they can experience any sexual pleasure. So in men the most common cancer related sexual problems we see are erectile dysfunction, loss of desire for sex, which often goes along with the disappointment about the erections but maybe hormonal in the case of hormonal abnormalities, trouble reaching orgasm, and men reporting that they can have an orgasm but the intensity of the pleasure is weakened. Now, certainly there have been attempts to spare erections by creating nerve sparing pelvic surgeries to avoid the prostatic nerve plexus. After nerve sparing surgery, men are sometimes given therapies to help them get frequent erections. The most common thing is to give them penile injection therapy so that they have erections a couple of times a week. And the goal is to get fresh oxygenated blood into the penile tissue which might help prevent atrophy of that tissue and might help promote a fuller recovery of erections after nerve sparing. It's still controversial area as whether this actually helps. Some men take pills to promote erections daily and a few men also use vacuum devices to try to get erections. And although that might not promote blood flow, it may actually help prevent some penile shortening that is seen often after radical prostatectomy. With radiation therapy, all of the techniques to try to focus radiation in a smaller area with less damage to surrounding tissue, like brachytherapy or using computer-guided imagery for prostate cancer, try to spare erections. The problem is that when you look further out and don't just look in the first six months or year after, still a lot of men end up with some decrease in the quality of their erections. When men need hormone therapy for prostate cancer, there have been attempts to give it intermittently until PSA goes down close to zero and then stopping it for a while and watching PSA and hoping that during that interval, the man can regain sexual function. That works sometimes, but a lot of men just don't regain sexual function when they're off their hormone therapy. Another tactic has been to use androgen-blocking drugs alone for advanced prostate cancer. And again, you know, there is no one type of modification that clearly is optimal in terms of prolonged survival and sparing sexual function. Now you might wonder why am I talking about the emperor's new erection. You probably all remember the fable of the emperor in China who was told by some con men that they had made him a beautiful new silk suit. But in fact, he was naked parading down the street. And I think our literature on recovery of erections after prostate cancer is kind of similar, and I often call it a medical fairy tale. If you want to have a good result, you take your sample from a tertiary referral center that has the best surgeons, the best radiation therapy technology, and the most experience. Then you only include men in your study who are under age 60 to begin with, are in very good health, and had very firm erections before their cancer. And this is clearly not the usual population of men who get prostate cancer. Then to measure your outcome, don't use a standardized scale, for example, the international index of erectile function or some of its short forms that are used very routinely in research. Instead, have the surgeon ask the man how he s been doing in his sex life since surgery. And in many of the early studies, men were called potent, and I don't like that word very well, but urologists still use it, if they could get their penis into, as I say, the desired orifice at least once since cancer. Of course, most men who come to erectile dysfunction clinics for treatment would meet that criterion. Maybe they can get a partial erection and sometimes we call them stuffers rather than stickers, and they can manage to begin intercourse and maybe even reach a climax, but it is certainly not satisfying to them. And also lately, in later years since we have had all these medical treatments for erections, men who are using them are included in the success group and benefits less than --- you follow them for less than 12 months, since they got radiation therapy and as long as possible if they got surgery. And the reason I get upset about this is, I think, we tell men based on these articles, a very unrealistic story about whether they re likely to recover erections. Furthermore, with any of these pelvic cancer treatments, erections aren't the only problem and, in a big survey that we did of around 1,200 men with prostate cancer from a registry at the Cleveland Clinic, about 45 percent reported that they had low desire in the past six months, 17 percent said they tried to reach orgasm but couldn't, and 28 percent said they had orgasms but they were weak and unsatisfying. The partner is also very important. Most of these older men do have partners. If they're not married, it's very easy for them to find someone to date 'cause

3 they're in the buyer's market. But of those men who had a partner, about two-thirds said that she had at least one sexual problem. The most common was that 42 percent of the women were reported to have lost desire for sex. And we found in other studies that a partner who is motivated to resume sex is a very important component of a successful outcome. Now, we didn't measure pain in our study, but in other series at least 9 or 10 percent of men report that they have genital pain after prostate cancer, often during ejaculation or sometimes just when they get an erection. And we also know now that a lot of men report that their erection is shorter after prostatectomy so that's true in 68 percent of men in one of the studies. And although it may not really change their sexual function, it does change their self-image and men really worry about that. Now, we have all these different treatments nowadays to treat erection problems after prostate cancer but the truth is that there aren't that many men who use them successfully. And this table compares our data from the big survey I just mentioned to you, and the five-year data from the prostate cancer outcome study, which had a similar number of men from a variety of men from the community. And at the time that these studies were published, the only medication that was available in pill form was Sildenafil. And you can see that a great majority of men --- well, not a great majority but a large group of men, were willing to try pills. And so the problem is that only 16 percent in our study, and 13 percent in the other study, said that they greatly improved their sex life and a larger group was still trying to use them but I think with a lot of frustration. So the truth is that, any of the pills that are on the market now work very well for men who can get almost a full erection, but they don't work well for men who have very little erectile function after prostate or other kinds of cancer treatment, and need to get from 20 percent to 100 percent. Another common treatment is the vacuum device in which a cylinder is placed over the penis. You pump out the air with either a hand or battery-powered pump and that makes the penis erect and then the man slips one of many different types of rubber-type bands on the base of his penis which retains the blood in the penis and his penis will be a little cool to the touch and blue-looking because this is venous blood. But it does work and we found a lot fewer men were willing to try vacuum pumps even though somewhat more men said that they were helpful in a similar, you know, percent of men were still using them at the time of the survey. But this tends to work well for men in a long-term relationship. A lot of older men who might have a new dating partner aren't very comfortable telling her that they are bringing in their vacuum pump. Then, there was a suppository that's still on the market that tries to infuse prostaglandin E1 into the tissue of the penis through the urethra. And unfortunately, it works for very few people. For those --- when it does work, it is great, but it is really not a very popular treatment because of that. There is injection therapy which is one of the most effective treatments. But as you can see, less than a quarter of men were willing to put a little needle in their penis and inject themselves with a medicine to create an erection. And unfortunately, although it has one of the highest rates of effectiveness of these medications, if you look not only in our survey, but in surveys of non-cancer patients, only about a third of men continue using it beyond a year or so. So, it may work but it's a hassle. And then surgery to implant penile prosthesis is becoming much more rare because we have all these other treatments that are reversible but there is nothing in our armamentarium that equals the satisfaction rates and the continued usage rates of the penile prosthesis. And what I do see is men cycling through these different treatments and finally getting fed up and saying, "Okay, I'm going to have surgery." However, if they've had a large cancer surgery, they often are not too keen on having any other kind of surgery in their pelvic area. So, to summarize, men want a pill, but they're more satisfied when they have invasive treatments that actually work better. And there is no reversible treatment that equals satisfaction rates with an inflatable penile prosthesis. And what we found is that men who are willing to try something beyond a pill, so they tried at least two treatments, were those who are more likely to actually have successful sexual rehabilitation. Now in women, we see a different set of problems. We also see low sexual desire. But one of the most major problems we see in women is vaginal atrophy and along with that, vaginal dryness and pain during sexual activity. Women also may feel unattractive although I think that that's been somewhat over emphasized and I think in some surveys that we've done, rates of not having sex because you feel unattractive to a partner are fairly equal between men and women and affect maybe only 15 to 20 percent of either group. Orgasm problems tend to be secondary to the fact that if you're not in the mood for sex and it hurts it's going to be very difficult to reach an orgasm. Now in general, if we look at women in the community who haven't had cancer, whereas in men we see ill health and aging as major factors in sexual problems, in women we see psychosocial factors as more important. With aging, the only problem that becomes more common is vaginal dryness. And ill health is less of an issue for women in terms of a factor predicting sexual problems. However, after cancer, premature ovarian failure for women who weren't at menopause is a very major predictor of sexual problems and even women who were menopausal often have worse pain and vaginal dryness leading to a loss of interest in being sexually active. Also in women, chemotherapy is one of most common cancer treatments that cause sexual problems, whereas it rarely is a major factor for men. But again, pelvic radiation therapy, bilateral removal of the ovaries, or surgery that removes some of the pelvic organs are all things that can cause sexual problems. There's been a lot of focus on androgen hormones, testosterone and its cousins that are made in the ovaries and adrenal glands. Again, I tend to think that the androgens and loss of androgens when women have ovarian failure is very much exaggerated as a

4 major cause of sexual problems, but it may contribute. Some women who have pelvic radiation therapy that can cause scarring and pain with intercourse in the vagina, and those who have bone marrow or stem cell transplant from a donor and end up with vaginal graft-versus-host disease, really have some severe problems. Pelvic surgery also can sometimes remove part or all of the vulva, vagina, or other organs that may contribute to sexual function. And of course breast surgery removes one of the erotic zones for a woman and even with cosmetically beautiful looking breast reconstruction, women no longer have the erotic sensation from the nipple and if that was important in their sexual arousal, that's a significant loss. So, if we look at premature ovarian failure, or for women who were menopausal and might have been taking estrogen and are told to discontinue it after they get something like breast or uterine or ovarian cancer, what we see is the symptoms are vaginal dryness, a loss of vaginal stretchiness and elasticity and you have to remember that when a woman gets sexually aroused, she gets something like an internal erection and the vagina actually becomes a third deeper and the lining produces the drops of fluid that make intercourse comfortable. So with reduced blood flow you see a loss of that response. We also see that these women are more vulnerable to getting vaginal or urinary tract infections and when they're repeated and chronic, that can really interfere with being sexually active. And also that women who experience pain with sexual activity or vaginal penetration, often tense the muscles in the pelvic area, and that exacerbates the whole syndrome because the more tense they are, the more tightened dry penetration is, and then you have the friction that sets up this whole vicious cycle. And the pain with sex, I think is often a major factor in loss of desire. Now with pelvic radiation therapy, immediately afterwards, for example, with cervical cancer, we see that the vaginal walls can actually stick together or agglutinate or you can get vaginal radiation ulcers or later stenosis, where a band of tight tissue midway up the vaginal barrel makes it impossible to have penetration beyond that point. So, these are all things that we can see, and thus, women who have pelvic radiation therapy are even more likely to have problems with pain. We also see that the vaginal mucosa once radiated are less responsive to replacement estrogen although it can still help. We see the loss of the elasticity of the vaginal walls with the fibrosis that occurs as the radiation irritation heals and we also see that, you know, if these women were menopausal and then have radiation on top of it, they often have some really nasty pain syndromes. I mentioned vaginal graft-versus-host disease after bone marrow transplant and particularly now that we're doing a lot of stem cell transplants where we use colony stimulating factor, the combination seems to be particularly likely to promote vulvar and vaginal graft-versus-host disease. So as many as 50 percent of women may experience this. And it starts with --- with --- with inflammation, then reddening of the vulva and pain on the vulva. And from there, you get vaginal adhesions, like filmy bands of scar tissue that go from one side of the vaginal barrel to the other and sometimes stenosis as the inflammation progresses. Now, especially when caught early, there are some local salves and creams that can be very helpful. For one thing, systemic therapy with an immunosuppressant drug, just like you do for any GVHD that's severe, can help but also local estrogen cream, topical steroids, and topical cyclosporine are sometimes used, along with vaginal dilators which you are kind of rigid, phallic kind of shape tubes that you can put gently into the vagina and press against the adhesions and gradually stretch them out or get rid of them. It's important not to do this too vigorously 'cause this tissue can be delicate and you don't want to end up with the fistula in between the vagina and the rectum. A few people have tried surgery followed by stents and dilation but it's really scary to operate on tissue that has a GVHD process going on in it in terms of poor healing. Now, in women in terms of loss of pelvic organs, women with vulvar cancer, if it's more advanced may have to have the entire vulvar removed and then they have the sense --- the sense of shame at how their vulvar looks. They are dealing with the loss of the clitoris, the most sensitive part of the woman's genital anatomy in terms of sexual pleasure and also even the vaginal entrance often gets narrow, so penetration is painful and needs to be dilated. A lot of women may be able to have a partial vulvectomy and some women actually have reconstructive surgery done similar to some of the breast reconstruction to give them some padding and the cosmetic appearance of having more of a vulva. Vaginal reconstruction for pelvic surgery can be done with a variety of different modalities. You can have a part of the intestine, but you may have problems with odor and excessive discharge. You can use split thickness skin grafts but then there's the issue of maintaining them and they're not healing up so that the vagina gets tightened and actually is lost again. And then with total pelvic exenteration, some women actually have reconstruction with skin and muscle flaps. With any of these reconstructions, you're not going to have normal erotic sensations inside the vagina, so that's another issue. Women who have either surgery to remove the bladder, surgery to remove the lower part of the rectum, or a total pelvic exenteration may have choices nowadays of having a urinary ostomy or colostomy, or having internal reconstruction of the neobladder, or reconnection with an internal pouch of the intestines. One problem you might think that it's always better not to have an ostomy, but with ostomy pouches it's easy to control odor and leakage. But with some of the reconstructive options, women have incontinence particularly at night and may have to wear a pad and this may be an issue for them in terms of concern during sexual activity as well.

5 Now, of course, breast cancer was the first type of cancer to get attention in terms of sexual side effects. But after all these years, one thing we've learned, is that we --- we hope that having, you know, lumpectomy and breast reconstruction would minimize the sexual problems that women experience after breast cancer. But what we found is with all these choices, the type of breast surgery really isn't a very good predictor of whether a woman stays sexually active or how many sexual problems she has. As long as the woman feels comfortable with the type of surgery or reconstruction that she has chosen, they seem to do pretty well. And although women who have conserved their breasts or have reconstruction will rate themselves as looking more attractive, especially in the nude, they don't have sex more often or enjoy it more. The main factor for sexual dysfunction after breast treatment --- as after breast cancer treatment, is chemotherapy. And the chemotherapy for women who are not menopausal puts them into a sudden menopause with all the vaginal dryness and loss of desire problems. And there's been a lot of, I think, misconceptions about some of the hormonal therapies. Tamoxifen actually acts like a weak estrogen in the vagina and genital tract. That's why it can cause uterine cancer actually. So women who take tamoxifen actually have less vaginal dryness than women who are not on any hormone therapy. Raloxifene also in studies doesn't seem to be associated with any problems with vaginal dryness particularly or loss of desire. But now that we're using the aromatase inhibitors, they, unfortunately, do worsen vaginal atrophy and dryness. And so women who are taking them tend to have more severe dryness and pain problems and we need to work out ways to treat those as conservatively as possible, since even giving women vaginal estrogen may sometimes get nothing to the circulation to counteract the positive effect of the aromatase inhibitor. Now what can we do for women who have dryness and pain? Well, for one thing, most women don't get advice on how to use non-hormonal lubricants and moisturizers optimally. Moisturizers are either sometimes polycarbophil gels or gels made of other kinds of materials. They are often put in a tampon type applicator and the women are supposed to use them 3 times a week before bedtime. They re not something that you use just when you're going to have sex. Some are suppositories also. And I think it may be less important exactly what the chemical formula is. What's more important is using some kind of a heavy duty moisturizer several times a week so that the vagina stays moist. Then, when women are going to have sex, they should use an extra lubricant, water-based or silicon-based, without any extra perfumes, and I usually advice against that ones that you blow on and they get warmer too. Now, the polycarbophil-based vaginal moisturizers in one study took up to two months to have their full effect; in another study, had their full effect after a week. Some women complain they get too much vaginal discharge, but we try to counsel them to wear a mini-pad and disregard that since it s going to probably drop off over time. For vaginal --- for women who use vaginal moisturizers and lubricants properly, and we tell the women don't go putting your lubricant on in the bathroom, keep it by your bed, incorporate it into your foreplay. Have your partner put the lubricant inside your vagina and vulva as part of caressing, and do the same for your partner's genital area so all surfaces are lubricated before any penetration. And keep it there in case you need more cause even the best lubricant just going to dry out. So, if women are doing all those things and they're still having pain and dryness, then it s time to consider low dose vaginal estrogen. And it seems like the most controllable ways to give it are in a vaginal ring or a tablet that have very low doses that are time released. And we need safety studies particularly in women with breast cancer, uterine, or ovarian cancer to see if we can give these without increasing the risk of recurrence. And gynecologists tend to think we can and oncologists tend to be leery of it, so women get conflicting advice. In addition, I often work with women with graduated vaginal dilators. Why? Because they are kind of a biofeedback device. It's not that I think we're always stretching out the vaginal tissue. In fact, there is very poor evidence for whether dilators actually do that. But I think that we help women feel that they can control the muscles at the vaginal entrance and also have something inside their vagina without pain starting with the small dilator and working upwards. So, if women just get a waxy white dilator and some KY jelly from the nurse and radiation therapy, 90 percent of those dilators go into a drawer and are never seen again. So we need to work on how to counsel women properly and use dilators that are more acceptable to women. And what we don't know, for example, is, if women got regularly sexually aroused through self- touch or partner stimulation, would the vaginal expansion and blood flow, work as well in keeping the vagina from atrophying as mechanical stretching would do? So there's a lot we need to learn about female anatomy. This slide shows you an example of some of the different dilators that women can buy on the internet or without any prescription. And I --- as I said, have them use the dilators often with a lot of lubrication, and just with awareness of tension and relaxation of the muscles around the vagina using the old Kegel exercises, and then learning that they can have something in the vagina without it hurting. And we also sometimes will counsel them on positions to use; positions for penetration that minimize the penis going in very deeply and give the women control over the angle and depth of penetration. Now loss of desire is the most complex and difficult sexual problem to treat in women and because look at all those factors that can contribute, the stress of having cancer, mild or moderate depression, chronic fatigue that's so common after chemotherapy or radiation therapy, sometimes for months or even a year afterwards. Relationship issues that might have been simmering along and when you get a severe trauma like cancer, may get worse so

6 there's more anger and tension, body image changes and feeling unattractive, pain that we've been talking about with the ovarian failure. And also women are often given multiple medications that they stay on after their cancer treatment, antidepressants, and the anti-anxiety drugs that we know, decrease sexual desire as side effects, pain medications that if their opiates can also contribute and even some of the anti-nausea medications. So we need to identify those risk factors and think, you know, what can we do to counteract the ones that are present? We also can enhance desire by helping women think, what usually got me in the mood for sex before my cancer? For someone women it's physical sports or dance, or having an intimate talk or cuddling, or romantic interlude with the partner, or women who are comfortable with reading erotic stories or seeing at least an R-rated movie with the good love scene, or having sexual fantasies can use that to stimulate their own internal desire. We have to make sure that a couple has good skills to communicate with each other about what the women likes in sex, and that the partner knows how to touch her in ways that are stimulating. We need to treat relationship conflict in depression. We need to very aware of changing medications or eliminating them if there no longer really needed that could be interfering with sex, and treating the sexual pain in vaginal dryness. Now, there have a number of studies published about replacing androgen in women and there is a drug available in Europe that wasn't approved by the FDA that is an androgen patch. But it only works better than a placebo at doses that are higher than a woman's natural testosterone levels. And there are some problems with this whole idea. For one thing, a number of large community studies of naturally menopausal women, and a couple of studies of breast cancer survivors, show that a women's own natural testosterone levels or other androgen levels, are not correlated at all with whether she reports sexual desire or sexual problems. We also see that in the randomized trials of testosterone patches, there was a very large placebo effect, and they never asked the women if they could tell whether they were on the drug or the placebo. And chances are they could since the drug has side effects. Well, if a woman thinks she s on the real drug, she is going to have much more of high expectation that it's going to work. And if she thinks she's on the placebo, then, you know, she s going to be disappointed. So, if that actually is occurring, that could explain why only a high dose of testosterone works 'cause you're going to have more side effects and it could account for all the differences between the placebo and the drug. And most assays to measure testosterone levels in women are not reliable because the levels are so low and the assays are meant to measure men's levels which are much higher. Now, the other problem is that androgens increase breast cancer risk. We know that women both before and after menopause who have higher natural androgen levels, have higher risk of breast cancer. And that's been shown in a number of studies. There have also been studies of women who were diagnosed with localized breast cancer and they looked at those who had the highest natural testosterone levels. And they had a significant higher risk of recurrence as they were followed for five years. We also see in studies in Europe of different hormone replacement regimens that the more androgenic they are and the greater the exposure, the higher the risk of breast cancer. And we also know that when we give women androgens a lot of them are metabolized to estrogen. And we know that estrogen in --- increases women's risk of breast cancer. So for all those reasons, I think that androgen should not be prescribed to women who've had breast cancer, or those who are in high risk groups like women with BRCA1 or 2 mutations, or women who have had Hodgkin s Disease, or osteosarcoma, who've had chest radiation as a children or teens and have a very high risk of breast cancer later on as a second malignancy. Now, what do we do? We have some interventions that work. But they don't get out to the patients that need it. So I think that it's very important to have multidisciplinary clinics that treat these kinds of problems for cancer patients. And you know, just doing a medical treatment or just doing counseling doesn't work nearly as well as cooperating together because they're both medical and psychosocial factors in these problems. We need to decrease the stigma of counseling, in general, for cancer survivors. And we need a trained cadre of professionals or oncology nurses and social workers who deal with lots of areas of quality of life can certainly do a lot of the basic sexual counseling. And we need to find a way to make these interventions cost effective and disseminate --- disseminate them out into the community, particularly our underserved patients. So who should identify these needs and problems? Well, I sympathized with oncologists who just don't have time in a busy clinic to do sex counseling. But, what they can do that's very important is bring up the issue because the physician's endorsement of a problem as being important is very powerful and allied health professionals then can provide the counseling and referral. So it could be a social worker, a psychologist if you're lucky, an advanced practice nurse or physician's assistant. But someone on the team should learn about the typical sexual problems for the cancer site you treat. Have a kind of a library of books, websites, videos, special handouts, and get comfortable asking patients about these problems and figuring out what's going on.

7 Then, that person should have a net --- referral network. Know the mental health professionals around who can help with the complex cases, maybe 10 or 20 percent of people who have more chaotic lives, less good copping skills, relationship conflict. Know who are --- who are the urologists around who treat erectile dysfunction and other male sexual problems, and who are the gynecologists in the community or the institution who are --- have the patience to deal with pain problems and menopause symptoms 'cause a lot of gynecologists are not happy getting these referrals. Barriers are: the lack cross- trained professionals who understand both cancer and sexuality in the mental health arena, the need to have interdisciplinary collaboration which is expensive, poor insurance coverage for the mental health services, and the ongoing stigma of psychotherapy or counseling. So many of our cancer patients have never seen a psychologist or other mental health professional and think it something shameful and bad. In the best of all worlds, in the major cancer center, we would have an in-house clinic they can assess and treat sexual dysfunctions with the multidisciplinary team as well as providing the infrastructure for research and training so that we can disseminate our knowledge out into the community where most people are treated. So in conclusion, sexual health issues aren't frivolous. Sexual dysfunction can have a really negative impact on quality of life and relationships. And oncologists need to help patients make informed choices about their cancer treatment and about the symptoms they have afterwards. We need better training of healthcare professionals and better research on intervention strategies. So thank you very much for listening to this today and I hope that what we've talked about can help you help your patients.