Genital graft-versus-host disease (GVHD)

Presenter:  Pamela Stratton, MD, on sabbatical from the National Institutes of Health

Recorded October 12, 2019 at the National Graft-versus-Host Disease Patient Summit

Presentation:  30 minutes, followed by 30 minutes Q&A

Summary:  Genital graft-versus-host disease (GVHD) can affect both men and women after transplant, making sex painful. Topical steroids and, in some women, estrogen is the usual treatment.

Highlights of Presentation:

• In women, genital GVHD can affect both the vulva and vagina and can be mild, moderate or severe
• In men, genital GVHD can make it difficult to achieve an erection or urinate
• Women should be screened for human papilloma virus after transplant (HPV) to reduce the risk of developing cervical cancer.

Key Points:

13:42  Genital GVHD can cause labial fusion – external scarring that causes the lips of the vulva to narrow or close: 

16:41 In men, genital GVHD makes it hard for the foreskin to retract, causing inflammation between the foreskin and penis

19:16 Male genital GVHD is treated with topical immunosuppressants 

23:08 Giving women the HPV vaccine after transplant increases their immunity to the disease and may reduce the risk of developing cervical cancer

25:05 Genital GVHD predicts lower sexual function:

38:44 How to find a doctor familiar with genital GVHD

Transcript of Presentation:

00:00  Introduction of Dr. Stratton:  It's a pleasure to speak to you today. And if you have any questions, please make sure that you write them down. I also will be at the reception because some people feel uncomfortable asking these kinds of questions and I am fine with your coming up to me later if that would feel more appropriate.

So, this clinical trial has nothing to do with graft-versus-host disease but I've done a variety of different things. I'm doing a study of the use of botulinum toxin and women with endometriosis related pain. I'm hoping that I'll help you better understand graft-versus-host disease, both what I know in women and the minimum amount of stuff that's known in men, and have you understand how that may affect sexual health and intimacy and what treatment options there are.

I have spent about 15 years working on graft-versus-host disease issues at the National Institute of Health in a chronic graft-versus-host disease study group that really looked across many organ systems. And that experience helped me think more in an integrative way.

01:29  Genital GVHD affects 25-50% of women after an allogeneic transplant:  So let's begin with female graft-versus-host disease. We think that it occurs in about 25 to 50% of women and it affects the vulva, the external genital area and the vagina, the internal genital area, but the lower, not the uterus or the fallopian tubes or the ovaries.

 Vulva chronic graft-versus-host disease seems to occur about seven to 10 months or later after transplant and vaginal chronic graft-versus-host disease can develop even years later. Most of the time, it occurs when you have graft-versus-host disease in other organs, especially the skin and the oral mucosa.

Thinking of the superficial surfaces. It can occur independent of that. I have seen cases where there's only been genital graft-versus-host disease and not any other manifestations of graft-versus-host disease. Vulva appears to be more frequent than vaginal and treating the external vulva does not actually prevent vaginal chronic graft-versus-host disease. So, it's important to distinguish external from internal. And sometimes women end up being confused, especially in the context of sexual pain where, again, because you don't see that part of your anatomy where the problem is.

03:07  Human papillomavirus occurs in 40% of women after transplant and the risk is higher in women with genital GVHD:  I also want to mention human papillomavirus. We've found that the cumulative incidents of HPV infection in the lower genital tract, was about 40% across women post-transplant. And the rate of HPV disease requiring treatment ranged about 15%. Vulnerable subjects are people who have had HPV before transplant or extensive chronic graft-versus-host disease or genital chronic graft-versus-host disease.

So, you might ask me what is HPV or human papillomavirus. When it occurs in the genital tract, it's the virus that's associated with cervical cancer and it can be associated with vulva cancer. And that's why it's really important to screen and detect that. And treating graft-versus-host disease may cause sort of an eruption in this viral infection there. So it's important to think about the two together.

In the study we looked at in the long-term survivors at NIH, we didn't find any HPV related cancer when standard guidelines for screening were followed. So that's part of the reason why I'm mentioning that. And this long latency of HPV reactivation, it may be several years and that means that there's a window of opportunity for augmenting immunity through HPV vaccination. Some of you may be aware that since 2006, it's been recommended that young women get HPV vaccination, and then a few years later it was recommended that young men get HPV vaccination. But like other vaccines, it's important to request that as part of your vaccination series after transplant. So I realize this is not what you naturally think about for graft-versus-host disease but it's another genital problem that ends up being important to think about.

05:41 Signs of genital GVHD during a gynecological exam:  So, what do I do when I look for graft-versus-host disease in a female? And on the right side of the screen, you will see sort of the external anatomy. What I do is I look for signs, that's what a clinician looks for. You come to me with symptoms and I look for clinical signs, which might be a rash or it might be fissures in the folds between the tissue. And I often gently use a cotton-tipped applicator to touch different areas to see if there's sensitivity there. And I use, in the vagina, one single finger to assess for scarring and then there's the speculum exam. Women understand what that means, where they put in the metal or the plastic contraption into the vagina in order to be able to see the cervix, and that enables us to look at the vaginal surface and to obtain both cytology, which is the Pap smear, and HPV testing, or cultures, if we're trying to distinguish graft-versus-host disease from infections.

So, we developed a classification system to help us better communicate as physicians, one to another, about what happens for graft-versus-host disease. And we classified it as mild, moderate or severe, where mild is a redness just on the surfaces that might appear like a lace-like red rash. Moderate may include breaks in the skin folds or open sores, and severe involves any form of genital scarring, either external where the surfaces stick together, or internal where the front and the back of the vagina stick together. Or there are bands, ridges, all of which can cause pain with intercourse.

To illustrate this, I have ... So, let me see. So this is the red area. As you can see, there is a fissure here. This is absorbed and you don't see the lips like you would here. And this is someone where everything was sort of scarred together externally, which is really uncommon but I want you to have a idea that it might happen. And this external scarring is really when the lips of the vulva scar together. And as you can see on the left side here, this is where it's all scarred together. And on the right side here, it's scarred right here so it narrows the opening and may make it painful during intercourse.

Internally, there can be vaginal scarring and there can be fine scars that when I've seen someone very early with vaginal graft-versus-host disease, it's like cobwebs. Or there can be ridges along the walls in the vagina or scarring of one wall to another, or I've seen sort of a curtain in front of the cervix. All of these things can make the vagina narrower or shorter than it usually should be.

It's hard because you as a patient might have a symptom but since you can't really sit to examine the area, you have to go to someone to look at this. And what we're doing is distinguishing menopause from graft-versus-host disease, to things that might happen with other biologics that are being used in your treatment.

10:27 How to distinguish genital GVHD from menopause:  For example, with menopause, the skin can be pale, it can be dry but it's not usually tender or painful to touch. There aren't any sores or open areas and there isn't any internal scarring but it can be narrowed because that kind of atrophy can happen with the lack of hormones.

With graft-versus-host disease, there may be redness. It's tender to touch. There may be open sores that look like herpes but when they're cultured, they're negative, so the herpes infection isn't seen there. There can be cracks in the skin folds and internal scarring.

11:13 How to distinguish genital GVHD from genital problems caused by drugs such as ibrutinib:  And with things like ibrutinib, there could be a rash just like herpes but is also culture negative. It's not usually tender to touch, there can be cracking. So I don't know. I'm mentioning this because as we continue to develop new treatments, there may be other biologics that have local skin reactions that we'll learn more about.

11:40   Genital GVHD is usually treated with topical immunosuppressants:  So, I'm going to divide treatment for female genital graft-versus-host disease into vulva, which will be both the surface things as well as whether or not areas stick together, or vaginal, the internal. And from my perspective, the important thing that should happen in the context of treating vulva disease is to recognize it early before scarring and things happen. And we usually use topical therapy of immunosuppressants, and we use really super potent ones like clobetasol. And we use that daily until it heals and then it's tapered off.

It's really important that that is tapered because if you continue to use it over the long-term, for fear of it coming back, it'll make the skin thinner and more fragile to damage with intercourse. And so there can be sort of a rebound of symptoms. So that's why you use it daily and then you taper so that you're not using it except later when you have symptoms.

It usually heals within six to eight weeks. And once it's healed, sometimes it can have caused thinning of the skin thickness. So using a topical estrogen may improve that thickness. However, if you've had a problem with blood clotting because of topical estrogen or have a hormone sensitive tumor, breast cancer in the past or something, it's important not to use estrogen. So that is a decision that ends up being made with your doctor.

13:42  Genital GVHD can cause labial fusion – external scarring that causes the lips of the vulva to narrow or close:  So, labial fusion, the scarring that can occur of things sort of healing together externally, can be complete, like I showed you that extreme example, or partial ,where I showed you that the opening was narrowed. And the complete scarring is best treated in the operating room where we gently make the parts be apart. But it's because it's a painful sensitive area, that it's much better to be asleep for that.

But I have also treated the partial labial fusion in the office by using a topical anesthetic and being able to simply peel it apart. It may sound gruesome but it's not. And for either, it's okay to have sex once it's healed. And sex helps the area stay open. And if you're not in an intimate relationship, using dilators may help. But if the pain persists or return or you recognize that the scarring return, reexamination is important to occur.

15:07 Vaginal GVHD is usually treated by topical therapies, rather than systemic immunosuppressive drugs:  So, for vaginal treatment, the fine cobweb scars are easily found and treated during an exam. We have found that topical therapy works best for the vaginal symptoms, just like it works best for the vulva symptoms. The systemic immunosuppression doesn't seem to effectively treat it.

So for the ridges, you can see on the upper right here, there is a ring. I have found that when I've inserted the ring in the vagina with someone who has sort of ridging down the vaginal wall, they come back in a week or two, and it's completely better. And it lasts for three months and it mechanically opens the vagina.

For scarring or narrowing or shortening, I have tended to use the dilators and have patients put both the topical immunosuppressant drug on the tip and estrogen, and then insert it in order to help to mechanically open it, and then later use the estrogen vaginal ring. It ends up being a bit of back and forth with visits to sort of check and make sure that things are moving properly, but it's tended to be very successful, even in challenging complicated cases.

16:41 Genital GVHD in males makes it hard for the foreskin to retract, causing inflammation between the foreskin and penis and making it hard to have an erection or urinate:  So what do we know about male graft-versus-host disease? There is very limited data. There have been maybe two studies done. But the major published study that I've seen is about 150 men who were alive for more than a year, where a dermatologist examined them, all of the men. 20% had genital skin changes. And of those, 13% had what we'd call the inflammatory skin changes like you see with graft-versus-host disease on the skin or in the vulva. 8% had an inflammation around the foreskin or glands. And part of what happens with that, from my understanding since I'm a gynecologist, I don't treat men, but I can tell you what I understand in talking to my urology colleagues. It makes it hard for the foreskin to retract and so there's like an inflammation between the foreskin and the tip of the penis that needs to be treated with a topical agent.

And why does that end up being a problem? Because the foreskin can become like a band around the glands and that can make it difficult when you try to have an erection or try to move it back in order to void. There can also be narrowing in the urethra, so that here can be scarring internally. And there's a higher incidence of it when, like with women, if you have oral, ocular or cutaneous graft-versus-host disease.

So, we worked to develop a similar scoring system, so we can talk among each other, for men and classify the lace-like rash as mild or the lace-like rash or the inflammation around the foreskin and the head of the penis as moderate. And any narrowing of the urethral opening or inability to retract the foreskin covering the glands as severe. Sort of thinking about the scarring piece as well.

19:16  Male genital GVHD is treated with topical immunosuppressants:  So, how do we treat this? Topical immunosuppressants, like we would do in females because the systemic doesn't seem to work. And if there's narrowing of the urethra or its opening or you can't retract the foreskin off the glands, it would be a surgical treatment. The narrowing of the urethra would be treated with something where you look inside the bladder and can cut the scarring as you go in. And the problem with retracting the foreskin would be to have an adult circumcision, which you would usually do under some sort of anesthesia.

We don't know how common these symptoms are for men after transplant. I think of this as a "don't ask, don't tell" situation where men don't come and say, "I have a problem there," and doctors don't look there. So we really don't know. Obviously, if there are these more severe problems with voiding, that would be ... You'd have to confess up about that, actually. So I think that genital chronic graft-versus-host disease likely contributes to sexual dysfunction in men and women.

20:42  A study found 2/3 of males have some sort of erectile dysfunction after transplant:  So, let's move on to talking about intimacy. In one survey of males after transplant, two-thirds of them had some sort of erectile dysfunction. And it was more frequent in men who had genital graft-versus-host disease for the reasons I've already explained. And only 40% reported sexual contentment. So it occurs ,and is under-reported. It currently should be considered in men who have difficulty voiding, blood in their urine or problems with sex.

21:33  80% of women have some sort of sexual problem after transplant:  For female sexual function, we know that it's impaired after transplant in 80% of survivors in the published information from almost a decade ago, they showed no significant improvement five years after transplant. So it continues to affect us after the physical and emotional well-being have returned to normal.

22:08  GVHD contributes to sexual problems after transplant:  And there are a lot of reasons for this. Systemic graft-versus-host disease causes fatigue, changes in appearance, which alter our body image and may contribute to some element of perceived unattractiveness. Genital graft-versus-host disease can affect sexual function as I've described. When the ovaries fail because of undergoing total body radiation or having primary ovarian failure after all of the treatments you've had in the context of transplant, that can make you menopausal and that also has an effect on sexual function. And there are other psychosocial factors like depression or self-consciousness. And some medications that you might be prescribed can alter both your desire and your ability to have an orgasm.

23:08  Giving women the HPV vaccine after transplant increases their immunity to the disease and may reduce the risk of developing cervical cancer:  So, we looked at a group of women after transplant and gave them HPV vaccine, because I wanted to see whether or not it would mount an immune response. And we compared clinically stable women after transplant, who are not on any systemic immunosuppression, to clinically stable women post-transplant who required systemic immunosuppression, to healthy volunteers And gave them all three doses of vaccine and then followed up at seven months and at 12 months.

And along with this, we looked at sexual function. And I'm happy to say that the majority of clinically stable reproductive-aged women after transplant, including those on immunosuppression, developed robust antibody responses that are similar to those that are seen in healthy women. And the full vaccine series can safely be administered to reproductive-aged women and I also venture to say men. And the current use of immunosuppression or the prior use of rituximab after transplant does not preclude vaccination.

So, in this, as I mentioned, we looked at sexual function and we used, I'm getting a little bit down in the details, we used a sexual function questionnaire that had a lot of different categories: interest, desire, arousal, all the things that you might think would be important, and looked at baseline sexual function. The sexual function questionnaire had been used previously in transplant populations and found to be reflective of what went on.

25:05  Genital GVHD predicts lower sexual function:  So we found that the baseline sexual function was lower for transplant survivors than healthy women. And it was similar for survivors regardless of whether or not they were taking systemic immunosuppression. And those that had been sexually active before transplant had higher sexual function.

However, with the sort of intensive sort of gynecologic and reproductive healthcare that comes when you enter into a study like this where you have someone who is looking to make sure that you're in optimized health, it actually helped improve sexual function. So orgasm was higher at 12 months for all subjects. Current genital graft-versus-host disease predicted lower sexual function for any woman post-transplant. And that meant that genital graft-versus-host disease, at any time point, was associated with lower sexual function. And higher sexual function occurred in survivors who were sexually active before transplant. And sexual function was improved in the one year period for all post-transplant females regardless of their prior sexual activity.

Clinically stable women after transplant, regardless of whether or not they're on or off immunosuppression, experience similar levels of sexual dysfunction and the largest affect on sexual dysfunction occurs in women with no prior sexual activity or who have current genital graft-versus-host disease.

27:01  Vulva GVHD causes sex to be painful:  So, putting sex and intimacy in the context of vulva graft-versus-host disease, vulva chronic graft-versus-host disease causes sex to be painful. You need to talk to your doctor if you have pain, bleeding or difficulty having sex. Early treatment can help the symptoms resolve quickly. It's okay to have sex once vulva graft-versus-host disease is treated and pain resolves. But if pain persists, reexamination is warranted.

27:32  Vaginal GVHD makes penetration impossible or painful:  For vaginal graft-versus-host disease, vaginal scarring makes penetration impossible or painful. So if you have pain, bleeding or difficulty having sex, an examination is needed. You cannot diagnose yourself. If you're treated early at the cobweb stage, sex can resume soon. With dilator use, once the dilator size of your partner is tolerated, sex can resume. It's okay to have sex once the area is healed. Sex can occur with the vaginal estrogen ring in place. If the pain persists or returns, reexamination is warranted.

28:17  Screening recommendations for female genital GVHD:  So, how do I put this together to think about what screening and care recommendations I would give you after transplant?

If you have any other graft-versus-host disease, mention any genital symptoms you have as possible graft-versus-host disease. For women, ask for referral for gynecology evaluation if you have any genital symptoms like bleeding, pain at rest, pain with sex or when you pass urine, if it's painful externally or if you have open ulcers. Males should ask for referral for a urology evaluation if you have any genital symptoms, like spraying of the urinary stream, difficulty retracting the foreskin, pain with intercourse.

Females, at an annual exam, you should be examined for genital graft-versus-host disease. And females, if you have extensive graft-versus-host disease or known genital graft-versus-host disease, it might be wise to do a gynecology exam every three months by a clinician with expertise in gynecology and post-transplant care. So for men, I have no idea on which to base the recommendations because this hasn't been studied very well in men.

29:58  Treatment for genital GVHD is generally topical immunosuppression and estrogen:  So, in terms of the treatment, generally, both the immunosuppression and the estrogen have to be prescribed by a doctor who is knowledgeable in genital graft-versus-host disease and can monitor treatment. And from my perspective, that's usually a gynecologist. Males, similar treatment is prescribed by a urologist who has knowledge of post-transplant issues. Any genital graft-versus-host disease for men or women is probably best treated with topical immunosuppression.

Females may use dilators, and if no contraindication, topical estrogen. Females with labial fusion or complete vaginal stenosis, that's treated with surgery followed by dilators, topical immunosuppression and topical estrogens. Males, scarring of the foreskin or within the urethra is treated with surgery. And for both men and women, the area should be inspected for evidence of HPV disease. The little cauliflower lesions that are wart-like.

31:17  When checking for genital GVHD, it is important to check for human papilloma (HPV) disease as well: So for HPV assessment, when a woman is looked at for genital graft-versus-host disease, it's important to inspect the whole genital area for HPV disease. Men can also be inspected in that way. Also, in addition to the inspection, Pap smear testing annually, especially if they had pre-transplant HPV or extensive chronic graft-versus-host disease or genital graft-versus-host disease. The HPV testing is performed for high risk types, those are the ones that are cancer-prone. And you're referred for assessment if there is abnormalities for colposcopy with biopsy of the area. I recommend everyone consider a HPV vaccination. And in terms of screening for other sexually transmitted infections, that's usually done based on risk factors.

32:19  Vaccinating women up to age 50 for human papilloma virus (HPV) may reduce the incidence of cervical cancer in women after transplant:  Given the high incidence of HPV and generally later occurrence, our results suggest that vaccinating women up to age 50, combined with periodic cytology and HPV screening, would be a practical approach to reducing HPV-associated squamous intraepithelial lesions and cancer in this population.

For sexual function, report pain with sex, dyspareunia, low sexual desire, any problems with arousal or orgasm. Treat any underlying hormone, meaning endocrine conditions or medical conditions. For females, consider vaginal estrogen or lubricants for pain with sex from menopausal changes. Treat genital chronic graft-versus-host disease and refer to a psychologist for individual or couples therapy.

33:16  Summary:  In summary, intimacy and sexuality can decrease the emotional distress and improve our psychological response to life-threatening disease and complications after treatment. This sexual response can be altered by chronic graft-versus-host disease, medications, psychosocial factors such as anxiety or depression, or body image changes, other life stresses, decreased self-confidence, fear of disease recurrence and concerns related to infertility. The impact of a serious illness on our sexuality and reproductive health is often not a concern expressed by patients undergoing treatment for a major medical problem. But I urge you all to consider this as part of your health. Thank you.

34:11 [moderator[]: Thank you so much Dr. Stratton. Really appreciate all that excellent information that you provided. We are now going to have a Q&A. So Dr. Zhou, I'd like to invite you up so that you can be a part of the panel. And just a reminder, if you do have questions, raise your hand and I'll bring you the mic. We need to have all of use the mic when we're speaking because we are recording the presentation. So we'll get going with our Q&A.

34:47 [audience] Should women over age 50 get the HPV vaccine?  I'm over the age of 50 but I did have HPV prior, like when I was 50. I'm 63 now. So should I still get that shot?

34:59 (Stratton] I don't see any reason why you can't. We don't have any information about your immune response because I didn't study people over age 50. But if you're getting the other vaccinations, they won't hurt you. The FDA recently approved giving HPV vaccination to women up to age 45. And that's the reason why I arbitrarily cut it off at 50 because I have data on the immune response up to age 50.

35:43  [audience] Blood clots and estrogen ring (E-ring): Okay. My other question is I ended up having, after my transplant, I had a blood clot three months later and then nine months later and I had gone to a doctor and I told them I had a history of blood clots and he gave me the e-ring and I ended up with a blood clot three months later. So, what is there for it? Because I had a hysterectomy. I don't have any fallopian tubes, any of that.

36:10 [Stratton] Well, so the estrogen ring, there are three different levels for the estrogen vaginal ring, a really ultra-low dose and two higher doses, and I don't know which dose you got.

36:25 [audience] Yeah, I'm not sure.

36:25  [Stratton] Using lubricants instead of E-ring:  So it's important to know what was prescribed because if it was a higher dose, then that could be a problem. There are ... If you had the lower dosing and still had a clot, you probably shouldn't take estrogen.

And there are other things that can be used for lubrication. There are water soluble lubricants, oil soluble lubricants and silicon-related lubricants. And in people who have studied this, in the context of breast cancer, which is a common time when you wouldn't be able to use estrogen, using the silicon lubricants appears to last longer during sex. And so, it's one of those things where you probably should ask the pharmacist because the names and the brands are always changing and when you go to ... I know that there's something called Liquid Gold or something like that or Liquid Platinum, that is one of the silicon-based things. But you can read the package but you can also talk to the pharmacist and use that, and that should make sex more comfortable.

So now if you've had a hysterectomy, you're not at risk of cervical cancer. In what I've looked at, in terms of long-term follow-up, it's really vulva cancer that also is increased in HPV-related post-transplant. And so that area should be looked at. It probably in addition to asking for HPV vaccine, you should make sure that you're still looked at and tested for ... a lot of times gynecologists now are saying you don't need to have a Pap smear if you've had a hysterectomy and you're over 60 or 65, but it probably would make sense for you to be looked at, assuming that everything else in your health is good.

38:44 [audience] How do you find a doctor who understand genital GVHD? So how do I find a doctor that understands that, and not just a regular?

38:49 [Stratton] Oh, that's a challenge. I just think you have to stick up for yourself and say, "I know that this is a risk and I want you to do this."

39:02 [audience] I mean, would they know what to look for if they don't understand?

39:05 [Stratton] Well, so there are a group of gynecologists who are really interested in what you call vulva diseases. And so it may be that going to a vulva disease clinic may be more helpful for you than going to a routine gynecologist and they would be more able to provide you with the help you need.

39:43 [audience] Is pelvic floor physical therapy helpful for pain with sex?: Have you seen success with people that have gone to, or women that have gone to physical therapy?

40:01  [Stratton] So, assuming that all of the genital graft-versus-host disease is diagnosed and treated, and that the area is not too narrowed or short, yes.

It's interesting, the thing that I gave you the disclosure for, I've just finished a study using Botox in the pelvic floor of women who have endometriosis-related pelvic pain and found that pelvic floor spasm is a very common finding in those women, and that some of them don't really tolerate the pelvic floor physical therapy because they have so much pain that they go through a physical therapy session and then they end up suffering in pain for a couple of days. And using the Botox actually breaks that cycle actually allows them to do that kind of physical therapy.

41:25 [audience] Treatment for fine cobweb scars in the vagina:  How do you treat the fine cobweb scars?

41:30 [Stratton] So, in the two or three times that I've seen them, I just have found them and wiped them away and then what I have done is put in a vaginal estrogen ring and have the patient come back a couple of weeks later. And in both circumstances, everything is fine then.

42:11 [audience] Success rate for surgery for cervix that is scarred over where they found cancer:  Hi. I just wanted to know if you have any history or records on people that have lost, or their whole cervix has been scarred over, and what the success rate is on surgery for that. Like my cervix is gone, it's scarred over. Like they can't even do a Pap smear anymore. And I finally had to go to a actual oncologist gynecologist now. In order to try to see if they could do it. And they want to do surgery but I don't know how the success rate is with that.

 [Stratton] It's not going to be very successful.

[audience] Only because they also found cancer, that's why I'm-

[Stratton] You mean cancer of the uterus, cancer of the cervix, cancer of the vulva, cancer of the vagina?

[audience] The vagina.

[Stratton]  I have seen this one other time and the appropriate treatment then was to actually remove the area that has cancer. And in this other case, the uterus was also removed because of the concern about whether or not there would be something hidden. Because when ... So the cervical opening and canal is smaller than a straw and so trying to open it and have it stay open, what we would do is find where the canal is, cut externally to be able to open it and then we kind of stitch back the area. But because it's only the diameter smaller than this cord, it's really easy for it to heal closed again. And if you have cancer there, what they want to do is get rid of it because-

[audience] And I have chronic graft-versus-host of the skin, so I have two things are against me right now.

[Stratton] Right. So, the reason why cancer of the cervix ends up being potentially a problem is that as it spreads locally, it can close off the uterus, which are the connection between the kidneys and the bladder. So if you have the area that's a problem removed, including taking the uterus wherever is affected in the vagina, then they can just do Pap smears of the vagina and see if there's any abnormal areas.

45:57  [audience] How do I resume sex after a bone marrow transplant and graft-versus-host disease when my partner is my caregiver?  Hi everyone. Thank you for all the comments and the information. I'm almost 60, I had a bone marrow transplant last year and I have some graft-versus-host disease going on. But it's been a long time since my husband and I had sex and I want to do it and I'm wondering like how ideally, are you guys doing it, what did it take to get it done? I really miss that part of our relationship. And so, all this medical stuff is good for me to know but I want to know the real deal. What's going on behind closed doors?

[Stratton] So from my perspective, if the area is okay, you should try it out. Take it for a test run. Not have high expectations at first. I don't know whether or not you [Dr. Zhou] have any other input in that regard.

47:06 [Zhou] The only comment I would say is you're definitely not the first person to ask that question, I assume others here would nod as well. And it is to say that as Dr. Stratton separated, sex and intimacy are not necessarily the same thing. And from what I've heard, a part of what you're missing is the intimacy in not, just say, penetrative sex.

[audience] Yeah. Well, he's my caregiver so the intimacy is hard.

[Zhou] Absolutely.

[audience] He sees everything from the medical side and then now we want to go be smooching under the blankets and I just want to get there.

 [Stratton] So it might be that you go to someone like Dr. Zhou because having a space to talk about that since it's really important to acknowledge the fact that he's your caregiver and your partner. And how do you go about that? And you have fears, and he likely has fears. I remember one patient I saw who had horrible skin graft-versus-host disease that sort of made her skin like leather, and made it so that she couldn't pull her knees apart so that it made it really hard for her, and her husband was afraid he was going to break her. He's a much bigger person and she had genital graft-versus-host disease at the same time.

So it was how do you manage all of those things? And they were really committed to working that out and they were able to successfully work it out. We were able to treat her genital graft-versus-host disease, get her skin disease better, end up having her hip mobility improve. And it worked and they were able to have sex. She is one of the patients in my CADASIL study.

49:34  [audience] Should you use clobetasol for genital GVHD and taper off it? I went to the skin graft-versus-host disease session and you talked about clobetasol, and he's like, "Well, you wouldn't want to use that in your vaginal region," and I went, "Ooh, I'm using that." And you said it was okay to use. But I'm wondering maybe it's the percent …

[Stratton] No.

[Stratton] It is the clobetasol that he uses and I respectfully disagree.

I don't think she's here in the room but there's a patient who came up to me who had reached out to me 15 years ago and she was having problems with her caregiver, her physicians thought that she had a chronic urinary tract infection. And she talked to me on the phone and she told me that today, that I listen to what was going on with her on the phone and told her to use clobetasol. And she had been suffering for six to nine months. She used clobetasol for one day and was better.

[audience] Okay. Okay. And you just ... And I've never tapered before so you recommend the tapering of clobetasol.

[audience] Yeah. So I do because it really makes the skin thin and that's probably what the dermatologist was really concerned about. And it's one of the things where I recommend that you sort of get familiar with your anatomy where propping a mirror up and looking, and putting it with a Q-tip where there's a problem. Sometimes it's sort of hard for some women to have that close relationship with their anatomy. But if the lips cover the area that is bothering you and you only put the clobetasol on the lips, it's not going to get better. So it has to be directly applied to the areas that really are painful and reddened and irritated.

52:00 [audience] How to overcome lack of desire for sex after transplant:  Hi. I'm eight years post stem cell transplant. So I took mine for a test drive like you said and it works. The problem is wanting to take it for a test drive is a huge issue with me and I'm wondering is there anything that will help that? I mean, my husband, poor man, feels like it's him and it's so not him. It's just me. Is there anything ...

[Stratton] So from a gynecology perspective, there's a question about whether or not if you had something like testosterone, which affects arousal.

That might help. And whether or not any of the medications you are on, might be altering your arousal and interest. But I also think that turning to Dr. Zhou might be a good plan because there might be other things.

[Dr. Zhou] There is one drug that is designed for increased woman's arousal or woman's desire and if you look at clinical trials data, it increased the number of days of desire I think by point five out of 30. So it was essentially useless.

For this situation, we often think about the idea of using it or losing it and you didn't use it for a very long time. And that desire, it's a habit. It's a habit that you can reform and it begins with starting to create time for the event. And it will feel uncomfortable, awkward, even silly at first, and that's okay because you were there before, and you can get there again. Having somebody who routinely meets with you, keeps you accountable and helps you and your husband have a dialogue and a conversation about what your fears are, what you are desiring, what he is desiring, can often be helpful.