September 28, 2022
Managing Vaginal GVHD
Presenter: Lenira Maria Queiroz Mauad MD, gynecologist and GVHD specialist at Amaral Carvalho Hospital in the state of São Paulo, Brazil.
Presentation is 25 minutes long.
Summary: Genital graft-versus-host-disease can be a lifelong risk for female stem cell or bone marrow transplant recipients. The presentation reviews the symptoms of vaginal and vulvar GVHD and discusses treatments that can restore women to full sexual health and functioning.
Many thanks to Kadmon, a Sanofi company, and Syndax Pharmaceuticals, whose support, in part, made this webinar possible.
- Genital GVHD is quite common in the transplant population, but it is often underreported and therefore remains untreated. To prevent more severe complications of vaginal GVHD, patients should report any symptoms promptly.
- Genital GVHD can appear or persist even when GVHD in other organs has been successfully treated. The cumulative incidence of genital GVHD can also increase over time so lifetime monitoring is recommended.
- Women undergoing a bone marrow or stem cell transplant should have a baseline gynecological review. This will be helpful in assessing any subsequent changes and accurately diagnosing genital GVHD versus other problems.
(06:43): The median time for genital GVHD to present is seven to ten months but it can appear much later as well.
(08:45): Genital GVHD has several symptoms including discharge, fissures, burning, and pain.
(10:01): External lesions are more readily identified, but gynecological exams are recommended to detect more serious problems like vaginal adhesions and deformities that can interfere with sexual activity and urination.
(12:21): Genital symptoms that need attention include fissures or small cuts, reddish patches, superficial vagina inflammation with burning, vaginal discharge, bleeding or pain during intercourse, changes in the appearance of the vulva, clitoral scarring, and vaginal narrowing or obstruction.
(13:00): Vaginal GVHD can be staged or classified as mild, medium, or severe to guide treatment.
(13:31): Non-prescription treatments can reduce irritation, itching, and pain.
(14:55): Topical estrogen can be an essential treatment to maintain vaginal health.
(15:52): Topical treatments should be combined with sexual intercourse or vaginal dilators once lesions and inflammation have resolved.
(16:52): Medical treatments include corticosteroids which must be used with hormones to prevent thinning of the vaginal walls. In the most serious cases, surgery may be required.
(21:48): Women can maintain intimacy and sexual function after transplant but they need time to recover at their own pace.
Transcript of Presentation:
(00:00): [Susan Stewart for Dr. Lenira Mauad] Introduction. Hello, welcome to the webinar, Managing Vaginal Graft-versus-Host Disease. My name is Sue Stewart, and I'm the founder and executive director of BMT InfoNet. I will be your host and moderator for this webinar.
I'd like to first thank Kadmon, a Sanofi company, and Syndax Pharmaceuticals, whose support, in part, made this webinar possible.
Please note that in order to clearly explain how graft-versus-host disease affects female genitals, the following presentation does include photos of the vagina and the vulva.
(00:36): It's now my pleasure to introduce to you Dr. Lenira Mauad, who has prepared this presentation for this evening. Dr. Mauad is a gynecologist and an expert on vaginal graft-versus-host disease. She's worked with stem cell transplant patients in the Amaral Carvalho Hospital in the state of São Paulo, Brazil, since 2008. As a leading expert on genital GVHD, she helped develop guidelines for the treatment of vaginal GVHD for the Brazilian Society of Cell Therapy and Bone Marrow Transplantation, and is known internationally for her work in this field. Dr. Mauad has prepared this presentation, but has asked me to present it since her primary language is Portuguese. Of course, we are presenting this in English. After I give you Dr. Mauad's presentation, she will join us for a question and answer period. So, let's begin.
(01:40): Stem cell transplants can bring hope but also obstacles for GVHD to patients. The story of each transplant patient begins with the act of a donor donating stem cells or bone marrow, which is an act of giving and an act of love. For this reason, it brings the hope of success. But over time, it also reveals a battle for life with many obstacles that need to be overcome. One of the obstacles is graft-versus-host disease or GVHD.
(02:15): I like this cartoon, it was posted by a girl whose name is Wendy. Wendy had leukemia and was transplanted with her sister's bone marrow. I'm not sure what happened to her. She posted this cartoon in 2014, and I haven't heard from her since. But Wendy did help a lot of people with graft-versus-host disease. Anyway, I think this simple cartoon nicely illustrates what happens when you have GVHD.
(02:43): The essence of GVHD involves donor cells attacking the transplant recipient’s body. At first, the cells in the patient's body welcome the donor cells, but the donor cells don't recognize the patient's cells as something that belong in the body, and thus they start to attack them. And as in this picture, for example, when a donor sees one of these skin cells, the donor cells think, "This is foreign, this is something I should attack. Stranger, I must destroy." That in essence is graft versus is host disease.
(03:16): Unless you are transplanted with cells from an identical twin, your cells and the donor cells will not be a perfect match. As a result, the donor's immune system will not recognize the cells in your body as something that belongs there. And it takes time for the donor's immune system to get used to you living with the cells in your body. Until then, there's a war between you and the donor's immune system. And this war is called graft-versus-host disease or GVHD. Fortunately, nowadays, we have learned a lot about this unpleasant consequence of transplant, why it happens and how to prevent it.
(03:59): Understanding female genitalia is important for understanding GVHD. Before we get started talking about vaginal GVHD, I think it's important that you understand and we review the various parts of the female genitalia. It's important that you know them so that you can examine yourself and stay in tune with your body. This is a picture of the outer region of the female genitals, which is called the vulva, and it includes the labia majora, the labia minora, which is here. Then the space between them is called the interlabial groove. The clitoris, which is the pleasure, sensitive part of the vulva is here. This area above it is called the clitoral hood. The vestibule is the entryway into the vagina and the urethra, which is here, which is where the urine comes out. Then the perineum is this area here between the anus and the vulva.
(05:17): This photo shows things in a little bit more detail, a little closer up. Again, this is the clitoris, this is the clitoral hood. This is the vestibule or the entryway to the vagina. This is the urethra, where the urine will come out. Then of course, the hymen and these other parts of the genitals.
(05:42): Again, this is a similar photo that shows it with the parts labeled. This middle picture shows you the vaginal canal. Here's the vagina, and it goes all the way up here to the cervix, which is about three inches or seven centimeters in length. Then the cervix looks like this, which is something that you'll see on a gynecological exam.
(06:09): Genital GVHD is common but underreported and often remains untreated. But why does genital GVHD deserve our attention? Because 24% to 69% of allogeneic stem cell transplant recipients can be affected by genital GVHD in varying degrees. The most important reason is that we have underestimated the number of those with vaginal GVHD, because many women don't report symptoms. After all, they don't even know them. Unfortunately, they get either not diagnosed, nor do they get treated.
(06:43): The median time for genital GVHD to present is seven to ten months but it can appear much later as well. So, when do we need to take care of it? When does it start? And when does it go away? We can see that the genital GVHD can begin earlier than 100 days post-transplant. But the median time to genital GVHD symptoms range from seven to 10 months. Sometimes they occur years after transplant. Late onset GVHD and late diagnosis are not uncommon, particularly in women who are not sexually active, and in those who don't have routine genital examinations or guidance about how to prevent genital GVHD.
(07:30): Genital GVHD is more likely when the donor’s peripheral blood stem cells are used for transplant rather than stem cell collected from the bone marrow donor, and can appear of persist long after GVHD in other parts of the body has resolved. So, who is at risk? Fortunately, we can identify some risk factors. The source of cells is one of them. The use of peripheral blood as a source of cells conveys a three times higher risk of genital GVHD than if we have cells from the bone marrow. GVHD in the oral mucosa and/or ocular conjunctiva, that is the mouth or the eyes, as well as extensive areas of skin GVHD also increase the risk of vaginal GVHD. These women should have a gynecological examination to detect genital GVHD, even if they don't have any symptoms in their genitals.
(08:19): But what you need to know is that as GVHD diminishes in other parts of the body and medication is tapered, GVHD in the genital area remains or even newly develops. This means that we need to remain on alert looking for genital GVHD, even when we think that GVHD is gone in other parts of our body.
(08:45): Genital GVHD has several symptoms including discharge, fissures, burning, and pain. So, what are the early signs of GVHD in the genitals? How do we know when it's beginning to develop? Some of these include abnormal discharge, extreme superficial discomfort, painful intercourse, and vulvar lesions.
(09:08): We can find some lesions such as fissures, that are tears, usually between the labia majora and the labia minora. With these, there is usually a lot of pain.
(09:20): You can also feel burning and observe these reddish areas, with or without erosions, which are similar to red glass called vitreous erythema.
(09:31): Or some painful ulcers can present in the vestibular area, and this too can be very painful.
(09:40): Here are some more erosions. This patient has abnormal discharge. She too needs to have a gynecological exam. During the exam of the vagina and cervix, we can find, behind the discharge, erosions in the cervix and the vagina.
(10:01): External lesions are more readily identified, but gynecological exams are recommended to detect more serious problems like vaginal adhesions and deformities that can interfere with sexual activity and urination. External lesions will be symptomatic, and the patient will ask for help. But particularly in patients who have not had a gynecological exam and are not engaging in sexual activity, vaginal lesions, which would cause bleeding or pain, have a greater chance of developing into a more serious problem as the adhesions narrow the vagina.
(10:26): There are late aspects and deformities that we should be aware of. For example, there are severe vaginal adhesions that cause narrowing or complete vaginal obstruction, scarring of the clitoral hood, partial or complete disappearance or fusion of the labia, and vaginal adhesions that can narrow and completely close the vagina.
(10:54): Without diagnosis or treatment, over time, the adhesions become firmer and the deformities become more evident, and clitoris is totally supplanted. There's some disappearance of and fusion of the labia. In late stages, adhesion and scars can interfere not only with sexual activity, but they can also interfere with urination. You can see the area where you urinate is completely covered over there.
(11:33): Vaginal adhesions can cause narrowing or complete closing of the vagina, the cervix may disappear and the vagina may become shortened and narrower.
(11:47): To prevent more severe complications of vaginal GVHD, patients should report any symptoms promptly. But maybe the more important point to be considered is how to prevent and avoid the consequences of genital GVHD. Patients should be instructed to go to the clinic when any symptoms appear, or as soon as GVHD appears in other parts of their body or worsens, especially in the eyes and the mouth.
(12:10): If women and their doctors and caregivers are attentive, the appearance of these lesions should be a signal of a possible diagnosis of genital GVHD. [Important genital changes shown on the slide that should be addressed include wounds, fissures, reddish patches, superficial vaginal inflammation with burning, vaginal discharge, and bleeding or pain during intercourse.}
(12:21): Genital symptoms that need attention include fissures or small cuts, reddish patches, superficial vagina inflammation with burning, vaginal discharge, and bleeding or pain during intercourse.
(12:22) Other changes that are important and need to be addressed include changes in the appearance of the vulva, scarring or buried clitoris, cobweb-like soft adhesions, firm adhesions, side-to-side firm adhesions with vaginal narrowing or obstruction. This is important, patients should receive instruction about the initial symptoms of genital GVHD and need to feel confident that they can count on their doctors to treat and solve their problems before genital GVHD arrives.
(13:00): Vaginal GVHD can be staged or classified as mild, medium, or severe to guide treatment. Your doctor will determine the treatment based on the grade of GVHD at the moment of diagnosis. For example, reddish mucosa is considered mild. If you have fissures in the vulva folds, that's considered medium range. And if you have labial fusion and all the late signs of vaginal GVHD, that's considered severe vaginal GVHD.
(13:31): Non-prescription treatments can reduce irritation, itching, and pain. What are your treatment options? For treatment, it's important to reduce the irritation of the genital skin by only using warm water for hygiene. And you should avoid perfumed lotions and perfumed soaps as well as tight underwear and clothes.
(13:53): What about non-prescription drug managements? Good skincare can be achieved with emollients like petrolatum, glycerin, and coconut oil that may be applied to the external genitalia to provide relief from itching or irritation [they should not be applied inside the vagina]. Lidocaine, a potent pain medication, when applied before hygiene or before sexual intercourse can relieve pain or discomfort.
(14:24): Premature menopause and hormone deficiency should also be considered in diagnosing genital GVHD. I'd like to draw your attention to the need to treat the changes caused mainly in the vulva and vagina by ovarian failure and premature menopause after transplant. Treatment is important not only to make the patient more comfortable, but also because the symptoms caused by lack of hormones can be similar to the symptoms of genital GVHD. And without proper diagnosis, [failure to treat the loss of hormones] may postpone proper diagnosis of genital GVHD.
(14:55): Topical estrogen can be an essential treatment to maintain vaginal health. Now, there are a lot of things you can do, a lot of topical estrogen forms available to use. They can be applied as a cream, taken as pills or applied with an estrogen ring that unfortunately they don't have in Brazil, but we do have here in the United States.
(15:16): Why do we need topical estrogen? Topical estrogen is essential not only because it increases the thickness of the vaginal mucosa, but it makes it more resilient and it also helps the recovery of the vaginal flora that facilitates sexual intercourse.
(15:36): Other treatment options that you have here in the United States includes Intrarosa, which is similar to hormone therapy. And also lubricants like a water-based K-Y Jelly, which is commonly obtained over the counter at drug stores.
(15:52): Topical treatments should be combined with sexual intercourse or vaginal dilators once lesions and inflammation have resolved. In order to prevent vaginal changes., these topical treatments should be combined with either sexual intercourse or the use of vaginal dilators, in order to be most effective. It's best to avoid intercourse, dilation, or medical action when inflammation is present in the vagina. It's better to wait for the lesions to respond to the drug treatment and improve before resuming intercourse or vaginal dilation. Failure to do so could make the vaginal inflammation even worse.
(16:30): Preventing vaginal scarring is important for sexual activity and cancer screening. Preventing scarring in the vagina is obviously important for your future sex life. But it can also be important, because scarring can make the cervix inaccessible and make a Pap smear or cervical cancer screening nearly impossible. As everyone knows, these screenings are essential for all women.
(16:52): Medical treatments include corticosteroids which must be used with hormones to prevent thinning of the vaginal walls. In the most serious cases, surgery may be required. The medical treatments used for vaginal and vulva GVHD are based on corticosteroids such as clobetasol, for vulvar lesions, and hydrocortisone in vaginal suppositories for vaginal lesions. Corticosteroids are effective in inhibiting the local GVHD process, but they can also cause more thinning of the mucosa, the lining of the vaginal walls. They must always be used with hormones. Tacrolimus, which also can be used in the vulva and vagina, doesn't have the same negative action in the mucosa, and it can be used if erosions or ulcers are present. When topical therapies fail to resolve the problem, surgery may be required.
(17:37): Women undergoing a bone marrow or stem cell transplant should have a baseline gynecological review. So, it's important to remember that knowledge is power and it's an important tool to prevent vaginal GVHD. Women who are about to have a bone marrow or stem cell transplant need to have a baseline gynecological review and should be educated about the possibility of GVHD in the genitals and their early symptoms.
(18:03): Genital GVHD can appear or persist even when GVHD in other organs has been successfully treated. Women should seek help as soon as they experience any symptoms of vaginal GVHD or when GVHD in other organs appears or worsens. More than that, both doctors and patients need to remember the risk factors for GVHD. They need to remember that even when GVHD in other organs is under control and systemic therapy is tapered, it's still time to pay attention and watch for GVHD in the genitals, because it often occurs in the absence of GVHD in other organs.
(18:44): So, what should we do? Asymptomatic women, women who are not experiencing any symptoms should get a gynecological routine evaluation, and doctors seeing these patients should include gynecological complaints in the routine evaluation of any transplant recipient.
(19:06): The prevalence of GVHD in the genital is unclear, which may reflect both the patients' reluctance to discuss genital symptoms and the practitioners' failure to require, both are important.
(19:24): The cumulative incidence of genital GVHD increases over time so lifetime monitoring for genital GVHD is recommended. It's important to know that the cumulative incidence of genital or vaginal GVHD can increase over time, which means that lifelong care and the search for early signs of genital GVHD must continue for the rest of the woman's life.
(19:42): Vaginal dryness due to lack of hormones should be treated to enable a proper diagnosis of vaginal GVHD. Even without symptoms, gynecological evaluation is crucial every six months. But if GVHD was not identified during the first three years after transplant, follow up needs to be done yearly. So, for all women undergoing transplantation, attention should be given to the need for vaginal hormonal therapy, because, as we've commented before, vaginal dryness due to the lack of hormones gives GVHD-like symptoms and makes diagnosis of genital GVHD much more difficult
(20:23): Self-examinations, dilators, and estrogen releasing rings can all help maintain vaginal health. Now that you know what genital GVHD looks like, it's time to examine yourself. You need to get to know yourself like no one else. Do a digital self-examination several times a week looking for pain, burning, bruising, deformities, and vaginal narrowing. You may notice small changes, and it's especially important to do this if you're not actively having sex, because otherwise you might not notice changes that are occurring.
(20:57): Dilators are important [tools to help] preserve vaginal functioning. You can order dilators or estrogen releasing rings on the internet and receive them in the privacy of your home. And they can help prevent the recurrence of vaginal GVHD. Before you use them, however, please consult your gynecologist or a physical therapist for instructions on their proper use.
(21:25): Many women are not in the habit of touching themselves. You need to know that it is very important to do so after transplant. Remind yourself that you have a new lease on life and you need to get to know your body better. Self-exams are an important way to keep yourself safe and to improve your health.
(21:48): Women can maintain intimacy and sexual function after transplant but they need time to recover at their own pace. There's no reason not to come back to life, back to intimacy and back to sexual experiences after transplant. Maintaining the intimacy and sexual function can help you detect early signs of vaginal GVHD and prevent vaginal adhesions. Stay alert, and in case of painful intercourse, bleeding, narrowing, penetration difficulty, and dryness, seek help.
(22:19): Sexual intercourse is an important part of life, but not everyone resumes sexual activity after transplant at the same pace. Sexuality and sensuality are affected by factors such as self-image and a decrease in libido due to a lack of hormones. Going through a bone marrow or stem cell transplant is hard, and all patients will need time to recover energy at their own pace. So, take your time. Don't compare yourself to how well others are doing or how your sexual life was before the transplant. Give yourself time to heal.
(22:58): You may find that changes from the transplant process can affect your self-image. You may no longer recognize your own body. There are changes like corticosteroid side-effects that can make you appear different and make you feel different about yourself.
(23:18): Sexual dysfunctions are common in the general population as well as with transplant recipients but often resolve over time. But don't worry, it's not just you. Sexual function is one of most prevalent and persistent long-term concerns after transplant. As you can see, the desire and many other aspects of sexuality are clearly affected by transplant. There are relationship problems, body image, changes in self-esteem, fatigue, low sexual desire, hormonal changes, infertility, and so on. These are all common and with help can resolve over time.
(23:57): Remember that transplant-related genital problems can be fleeting and corrected. So, what can you do to improve your sexual relationships? First, believe that this situation is fleeting. It can be corrected. Ask your gynecologist for hormone therapy, at least in the vulva and vagina. It will improve lubrication and make your intercourse less painful. Discuss your difficulties with your partner. Use lubricants or extra-lubricated condoms. Keep the intimacy and affection and contact normally associated with sexual intercourse, but not necessarily penetrative sex.
(24:39): This is Dr. Mauad's care line for patients. As you can see, it begins with a fight for the preservation of quality of life before transplant, during transplant and afterwards. This is a long-term process. Become friends with your gynecologist and make sure you get examined frequently by someone who understands both gynecology and graft-versus-host disease.
(25:09): Managing genital GVHD depends on early recognition and specialist treatment. In summary, the management of genital GVHD needs to be focused on early recognition and specialist treatment with at least annual gynecological examinations.
Question 1: How long does it take for the libido to return after transplant?
Dr. Mauad: It depends on if you are on hormonal therapy and your overall health – whether you have recovered from your illness and from the transplant. Sometimes you will need help from a psychologist, friends and/or your partner. The most important thing is you need to take care of yourself. ‘Make up’ with yourself, feel good with you in your new condition and the person that sometimes is different from the person before transplant. If you are sure of yourself, with your self-image and self-esteem, it will be easier. Sometimes patients push their partner away out of insecurity. He or she he can help you more than you imagine. Give your partner the opportunity
Question 2: When should pelvic physical therapy be added to the treatment regimen?
Dr. Mauad: Whenever possible. Physical therapy can help with pain, narrowing and shortening of the vagina and can help you understand how to use dilators.
Question 3: Do you have a protocol on how to follow women after BMT for early diagnosis of GVHD And treatment guidelines after diagnosis?
Dr. Mauad: Yes, I do. I can share with you papers and my own follow-up and therapy protocol. More than that, if you are a health professional, we can exchange experiences. Please email firstname.lastname@example.org and request it and I will send it to you.
Question 4: Do you have a recommendation for women who cannot use estrogen-based products because of a history of ER+ breast cancer? I am not having dryness, just soreness.
Dr. Mauad: If you don't have vaginal dryness, you may have vaginal shortening or narrowing. You may not need hormone therapy but physical therapy and dilators.
Question 5: Can you distinguish between lichen sclerosus, lichen planus and GVHD of the vulva?
Dr. Mauad: Good question. After BMT you can see both, lichen sclerosus and lichen planus – that is like GVHD – in fact GVHD is lichen planus-like. So, the treatment is the same.
Question 6: How can you live well with vaginal GVHD?
Dr. Mauad: It depends on the symptoms. Some late symptoms are difficult, but not impossible, to treat. Sometimes surgical release of scars, use of dilators, hormones and topical corticosteroids are necessary to restore sexual function
Question 7: Is there any medical procedures that can be done for extreme tightness of the vagina other than dilators, hormone inserts and extra lubrication? They didn’t work.
Dr. Mauad: There is still no scientific evidence for the use of laser therapy, but it may be an alternative. If there are vaginal adhesions they can be surgically removed.
Questions 8: Does vaginal GVHD ever go away permanently?
Dr. Mauad: Yes, it is possible. Most women who develop GVHD and are diagnosed and treated early do not develop permanent consequences and may have no further symptoms. However, they still need at least an annual follow-up. There are reports, and I myself have patients who developed vaginal GVHD up to 7 years after BMT.
Question 9: What can be done if my vaginal canal is closing? My husband is patient but he wants sex and he is driving me nuts. I am not interested in sex but I love him to death….
Dr. Mauad: You need to see your gynecologist and he/she will be able to say what is happening. You being wanted by your husband and loving him is a good reason to ask for help. Maybe the solution is simpler than you think – physical therapy, sometimes surgery.
Question 10: What can be done to correct vaginal atrophy?
Dr. Mauad: You need to see your gynecologist. If it is indicated in your case, the use of hormone applied to the vulva and vagina helps a lot.
Question 11: I was not examined or educated about this at all. I told my transplant doctor and I think he documented it and that was that. Years have passed and I’m probably in the “severe” category. I’m not sexually active and have zero libido. Is there any hope for me? Is it possible to be “too far gone” as they say?
Dr. Mauad: Unfortunately, little is known about the long-term complications of bone marrow transplantation. Few transplant centers in the world have specialized gynecological assistance and the doctors themselves are still poorly prepared to face this problem. Many women are still diagnosed at the stage of complications. It then becomes necessary to evaluate and decide what to do. Hormone replacement and surgical reconstruction are often necessary, but of course, it depends on the situation of each patient. Don't give up, seek expert help, is never too late. Some patients that you have seen in my presentations are very well nowadays. You can ask for information from BMT infoNet.
Question 12: Can I use tacrolimus ointment with estrogen topical or inserted estrogen? Was using tacrolimus ointment and it burned when applied.
Dr. Mauad: Yes, you can use them together. Tacrolimus is a great option but if your mucous membranes hurts, it can really burn. You can use tacrolimus in smaller concentrations. That can help. Estrogen applied locally, helps in the recovery of both vaginal and vulvar mucosa
Question 13: Why not start vaginal estrogen right after BMT for all women with high risk for genital GVHD? Chances are they will be amenorrheic after chemo.
Dr. Mauad: Yes, it is important. I usually prescribe Estriol (proper hormone for the mucosa) before and throughout the transplant, until they can start hormone replacement in more adequate doses. It keeps the mucous membranes of the vagina and vulva in good condition all the time. There is no evidence that this action decreases the occurrence of genital GVHD, but as I showed in the presentation, it doesn’t confuse the diagnosis, as the symptoms of lack of hormone in the genitals can mimic or delay the diagnosis of GVHD.
Question 14: What about the procedure called The MonaLisa Touch®? It is a minimally invasive laser treatment that rejuvenates vaginal tissue to improve vaginal dryness. Its purpose is to improve the health of your vagina. I was told this could help my clitoris. Mine is sealed or skin has covered it. I have mild GVHD.
Dr. Mauad: Yes, it can improve. There are not much data in the literature on its use in transplanted patients with GVHD, so I cannot say that it works, as I have no experience with this laser, but it is a promising possibility. Sometimes minor surgery may be needed to correct it. All my more serious cases, I treated initially with surgery and then with steroids and hormones. It works!
Question 15: What are your recommendations of use of long-term steroids vs topics vs topical tacrolimus? What are your recommendations for vulvar moisturizer?
Dr. Mauad: always start with clobetasol (0.05mg/g) or mometasone, associated with estriol, to compensate for the thinning of the mucosa caused by the corticosteroid. We don't have tacrolimus easily [in Brazil] so we reserve it for cases where the corticosteroid doesn't work and where we can't control the thinning of the mucosa. In addition, tacrolimus can be used at a lower dose of 0.01. Many patients complain of burning after application. As a vulvar moisturizer, Vaseline or coconut oil are good options – but only on vulva – not in vagina.
Question 16: Is complete loss of libido a side-effect of the chemotherapy and radiation treatments involved with BMT?
Dr. Mauad: Yes, mainly because these treatments lead to failure of the ovaries. No hormone production.
Question 17: My transplant was 18 years ago. I received no pre-transplant information about the possibility of vaginal GVH and was not advised to have a baseline pelvic exam. After transplant, I was specifically told to wait a full year before having an exam. I ended up with vaginal stenosis that required surgical intervention to correct and that caused extreme psychological trauma because the post-surgery therapy (use of dilators) was so painful. The effect of all this on my sex life has been devastating. What general advice to you have for longer-term transplant survivors like me who did not have access to all the preventative treatments that are available today?
Dr. Mauad: I'm very sorry!!! We've learned a lot about the complications. Many of the protocols that have been developed today are to avoid these consequences that we didn't know about before. We've only been studying genital GVHD for about 20 years. Treatments have changed, allowing more survival and consequently bringing complications that were previously unknown. Now we are more concerned with the quality of life. We not only want women to live longer as they are living, but to feel alive.
Question 18: Do you have recommendations on when to start monitoring pediatric and adolescent patients and how often?
Dr. Mauad: At the beginning of the treatment. I always talk with them, their families and caregivers. I teach self-examination and daily examination by caregivers. I ask them to use a daily moisturizer on the vulva, so they can examine themselves. But there is no way to do an internal, vaginal exam. So, I keep a close eye on them, every 3 to 6 months, and when they start menstruating spontaneously or with hormone replacement, I follow the beginning of sexual life to detect problems. And there are a lot of problems….
Question 19: Is there a need for vaginal hormone replacement therapy if you are in menopause and no longer on hormones?
Dr. Mauad: It is essential.
Question 20: Does GVHD of the vagina ever clear up or is it an indefinite problem?
Dr. Mauad:There may be phases of improvement and worsening. The most important is to maintain a functional vagina that allows for an adequate sex life
Question 21: I find that the vaginal treatment burns so badly. Is that normal?
Dr. Mauad:: Both corticosteroids and tacrolimus can cause burning, especially with a lack of hormones. Are you using hormones too?
Question 22: I have some patients that have acquired other primary cancers as a result of treatment. What are the risk factors for being diagnosed with breast cancer when using the estrogen creams?
Dr. Mauad:They are more likely to develop cancer - second tumor - because of chemotherapy and prolonged immunosuppression. In very young women, there is no way not to use systemic hormone therapy, always with great care and follow-up. For women over 40 years, the application can be topical with less systemic action without increasing risk. The changes induced by HPV in the cervix and vulva can be manifested by the use of local immunosuppressants and therefore the importance of prescribing the HPV vaccine. In Brazil, they are free by the public health system until the age of 45 for all transplant recipients.
Question 23: Through ISSVD (International Society for the Vulvovaginal Disease) you can find GYNs with experience with GVHD?
Dr. Mauad: don’t know. Dr. Pamela Straton who works at Bethesda, leads a study group on gynecological complications post BMT. I follow her publications and learn a lot from them.
Question 24: Are there specialists for vaginal GVHD?
Dr. Mauad: In Brazil we are three. In the USA, I know only Dr. Pamela Stratton and her study group.
Question 25: I take Osphena and stopped the topical hormone because the topical hormone causes my skin to become very sore. Is there another option beyond estradiol ?
Dr. Mauad: You can use Prasterone (INTRAROSA) once a day for 6 months taking a 2 month break
Question 26: What are side effects of topical estrogen?
Dr. Mauad: It can itch or cause an allergy
Question 27: Is there a time period that is too long to use topical steroids? How long should you give clobetasol to work before you stop?
Dr. Mauad:: Sometimes we need to use tacrolimus. Increase and decrease doses and formulations associated with topical hormone and always progressively reducing the doses.
Question 28: What is vaginal physical therapy? I don’t think many of us new transplant recipients have heard of it.
Dr. Mauad:Basically, it is exercise
Question 29: Is there a database or website where the GYN is able to access information when they are not familiar with vaginal GVHD? I’ve been to a couple of gynecologists who have no idea about or how to treat the symptoms of GVHD.
Dr. Mauad: See: Frey Tirri, B., Häusermann, P., Bertz, H. et al. Clinical guidelines for gynecologic care after hematopoietic SCT. Report from the international consensus project on clinical practice in chronic GVHD. Bone Marrow Transplant 50, 3–9 (2015). https://doi.org/10.1038/bmt.2014.242
Klasa, Ł., Sadowska-Klasa, A., Piekarska, A. et al. The management of gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation—a single-center real-life experience. Ann Hematol 99, 1361–1368 (2020).
Murphy, Jeanne et al. A Practical Guide to Gynecologic and Reproductive Health in Women Undergoing Hematopoietic Stem Cell Transplant. Biology of Blood and Marrow Transplantation, Volume 25, Issue 11, e331 - e343. https://doi.org/10.1016/j.bbmt.2019.07.038 1083-8791
Question 30: What is the treatment recommendations for lichen planus-like GvHD? Just use of steroid cream vs tacrolimus?
Dr. Mauad:Basically steroid creams and vaginal hormone replacement therapy
Question 31: Any advice for increasing libido?
Dr. Mauad: At first you can't feel pain during sexual intercourse. Ask your gynecologist if you need and if you can use hormone therapy and finally, be well with yourself and with your partner
Question 32: I’m on Jakafi can I use topical/or internal estrogen?
Dr. Mauad: You can use topical one.
Question 33: How doa I find a doctor who understands both GVHD and women's sexual issues?
Dr. Mauad: BMT InfoNet has a GVHD directory that lists GVHD clinics and sub-specialists in the U.S., including gynecologists who familiar with both GVHD and can treat patients regardless of where they were transplanted. You can view the directory online at https://www.bmtinfonet.org/gvhd-directory.This article is in these categories: