Nurses Conference 2013 - Monique Regard
I am Dr. Monique Regard. I am a pediatric gynecologist and I work with two other pediatric gynecologists. We work out of Valhalla and we have several satellite offices in Westchester. I think it is sort of beginning with this talk to let you know that on Wednesday one of my partners was in the OR calling me that she had a 12 year old who she had gone in for with an ovarian cyst and it looked like she had scattered a few...endometriosis throughout her pelvis at age 12. So, it is a disease that can strike very early. We are waiting for the biopsies to come back but we are thinking that the way this looks surgically this is most likely going to be endometriosis.
I am going to talk a little bit about how we as practitioners, as pediatric gynecologists handle a patient who comes into the office with pain and how we work......A little bit for those of you who do not know what endometriosis is or are new to the topic, it is considered endometrial tissue in the wrong place. I now describe it to my teenage patients, because they often want to know why I cannot see it on ultrasound, as blisters or chicken pox...I will say to them, "You know it looks like you have a little chicken pox blisters around" because that is what it is going to look like generally in adolescents. endometriosis should be viewed as a chronic [3:17 BLANK 3:26] girls come in at 17...by the time they are 25. . I tell people you know...then try the other one. There are those specialty patients who either have gastritis or may have Von Willebrands disease. We have a lot of girls in our practice with Von Willebrands disease. They technically are told they cannot use a non-steroidal but they can use Celebrex. So for those girls it is good to remember who may have been told, "Oh, I can't use any Motrin because I have Von Willebrands disease" Celebrex is okay for them.
There was a very nice study done on omega-3 fish oils. There was somebody who had determined that because of the inflammation in prostaglandins, the way it comes down the arachidonic acid profile that maybe fish oils would block some of the prostaglandins produced with dysmenorrhea. They actually had a very large study of 750 girls with dysmenorrhea in high school and they gave them fish oils every day and found out that they reduced the amount of dysmenorrhea complaints. And as an aside, there is also a good study showing that it helps with ADD. There are always advantages to taking your fish oils every day.
I use a fair amount of Lidocaine patches in girls who we do not want to put on the pill just yet and who have some discomfort. I have had some reasonable success using Lidocaine patches in the early stages or I will use it post surgical stages just to complement. I always tell people I just want to layer everything on. It is a good thing to know about. It has not been proven.
There are some lifestyle suggestions; smoking has been associated with prolonged dysmenorrhea, so counsel them for all sorts of reasons to reduce their smoking. Obesity, we have had - I think it is a trend - that there is probably more inflammation in obese girls. I think there is some feeling that we are seeing more obesity - more endometriosis in obese patients. It has not been worked out that well but we do have some studies suggesting that being overweight, with all that inflammation, may increase, I think they get disease anyway, but it may be worse with obesity.
So you have started with NSAIDs and they are still complaining that they are having pain. They say, "Now I'm really, really ready. I need to go onto birth control pills. So, endometriosis and hormones; endometriosis is considered an estrogen dependent disease so medical therapies are targeted at lowering their estrogen. We usually start with cyclic therapy and non-steriodals in any female patient with pain. Progesterone is the workhorse of the birth control pill. What is very interesting about progesterone is that they produce an anti-estrogen effect. They inhibit endometriotic implants. What is fascinating to me is I attended a lecture on the use of progesterone for preterm labor and they have an incredible anti-inflammatory quality and that is why they are starting to use them in preterm labor.
I am starting to suspect there has not been a lot of cross pollination between OBGYNs doing research in preterm labor and people doing research in endometriosis. But it may be that there is an anti-inflammatory quality to progesterones that helps with the inflammation of endometriosis. I would love to see these two research groups cross pollinate to look at the anti-inflammatory qualities of progesterone therapy.
We usually use a traditional pill that has a combination of estrogen and progesterone because when a girl goes on pills her natural estrogen levels will suppress to very low levels and she will not have enough estrogen to bone build very well and she is in her peak bone building years. We have this dual problem of we want to lower your estrogen but we do not want you to have osteopenia by the time you finish treatment. You want to be in a double therapy. There is newer stuff coming out saying you need to be on a 30 to 35 microgram pill for good bone building. So that is a unique need of adolescent patients.
We do have the NuvaRing and we have the skin patch each week. I do not typically pick those therapies for endometriosis in teenagers, but they are available. Monophasic is much better I think than triphasic. We want the therapy to be the same every week. You know, Ortho Tri Cyclen and Triphasil; I am not a big fan of triphasic pills in adolescents because I want it continuous. Later I want to do like six weeks in a row or nine weeks in a row for a lot of these patients and I cannot do it with a Triphasic pill.
Progestin dominant; these are some of the progesterones that are better and more progestin dominant that would be more efficacious in endometriosis. Dosages, again I hinted that we really want to avoid 20 microgram pills in adolescents. While it would be better for their endometriosis to probably be on a 20 microgram pill in those years unless we absolutely cannot manage and there are some conditions we have trouble managing on a 35 microgram pill, we want to try to stick to a 30 to 35 microgram pill. But you are going to have more side effects with that. Headaches can be one of the predominant reasons you cannot use a 30 to 35 microgram pill and there is more - migraines are more associated with patients with endometriosis so we get more kids with migraines who have endometriosis. We have to factor that in. Fluid retention, nausea, weight gain, some hypertension, emotional lability those are just the things you may get with a little more estrogen.
Now you will have the girl that cannot take estrogen so there has been several consults for like, you know, "I have terrible pain. I'm trying to take birth control pills but every time I do you know I have blindness in my eye with my migraines" something like that, "I don't know what to do". Well, those girls can take progestin-only therapy. If she has a risk for a clot, her mother had a blood clot, and she got tested and is known to be a carrier for Factor V Leiden for example. Complex migraines; that is anybody who has migraines with neurologic focal symptoms. If you have a migraine and during your migraine you cannot use your arm, or you cannot speak, or you cannot see out of your eye those are considered neurologic symptoms with your migraines. That puts you at increased risk for stroke with birth control pills. Those girls should not be on estrogen containing pills because of their increased risk of stroke. That certainly applies for adults as the risk goes up. They need to be on a progestin-only therapy. Then there are girls with persistent nausea, headaches, they just are not doing well and they would switch over to progestin therapy.
For progestin therapies we have the mini pill and the norgestrel which is Ovret. It is very hard to get on the market so typically Micronor, which is a breast feeding pill that was developed for breast feeding, and then you have the Depo-Provera, the IUD and the implant. My problem with Depo is after two years there is an osteoporosis warning so I do not really like to use it in adolescents because, again, they are bone building and that has got to be laid out against all the other things we are trying to do.
I love the IUD. I will talk about it quite a bit later. You should be aware there is a new three-year IUD that came out on the market, Skyla in addition to Mirena and it was so popular they ran out after four months. They are actually on back order and they are having to ramp up all their manufacturing because they just whipped through them much quicker than they expected. Then there is the implant which lasts for three years. I do not love it for endometriosis patients because there is unpredictable bleeding with the implant. Great contraceptive but if you are already bleeding and in pain every time you bleed unpredictable bleeding does not really help you.
Dysmenorrhea; we are going to kind of work through the different hormonal things. Then when should be consider laparoscopy? The American College of OBGYN recommends that if pain persists beyond three to six months you should consider doing a laparoscopy, if you are under 18 especially. If you are over 18 you have the option to give the patient Lupron for three to four months and see if the Lupron handles their symptoms appropriately and then they can go back on pills. I have had some issues with the Lupron in that my patients find that they really want to know a diagnosis so they do not love the idea of like "maybe I have it, maybe I don't" they just really want to get that settled. They have usually had pain for years and they kind of feel like they want to get to the bottom of it. Also anxiety is a major side effect of Lupron. I just had a girl, 20, this year we had the long talk and she said, "I'm going to do the Lupron" two shots of Lupron and her anxiety was just through the roof, she is switching over to surgery.
When to do it; we are more likely to be concerned if there is a family history of endometriosis. If you have gone to the ER multiple times and they keep telling you you had a ruptured ovarian cyst but you look at all the ultrasound reports and there is nothing except a little fluid in the pelvis. Fluid in the pelvis is normal and ERs discharge kids all the time saying, "She had a ruptured cyst" because it sort of answers their questions and nobody talks anymore. But a little fluid in the pelvis and you had a ruptured cyst and that is why you had pain and no evidence of a cyst on ultrasound is likely to be, if they have dysmenorrhea, you should be thinking about endometriosis.
Not going to school; we had a ten year old last year who had not been to school for six weeks and I scoped her because she had not gone to school for - I did not want to do birth control pills at age ten and she had a little spot of endometriosis. We took it out and she was back in school. Really early, early painful periods would be a concern for endometriosis, really focal tenderness like a very specific spot with painful periods. It is unclear to me because we do not scope those kids very often that if you have pain but no painful periods it is almost never endometriosis in at least teenagers. Dysmenorrhea, painful periods, really has to be part of the whole picture. Endometriosis is getting worse and worse and then pain when you are not having your periods plus painful periods - these are all things that make us more suspicious of endometriosis.
We think that the hereditary rate for endometriosis is considered about 35 percent. Should you take it out or should you buzz it? This is a big debate. The Endo Foundation has very strong feelings on this. There are other organizations that feel differently but this would be a typical that little blue kind of lesion that you see smack in the, sort of slightly to the right of center is an endometriosis lesion kind of typical of an early small lesion. I have adopted the excision technique when I can. There are some times when you just cannot quite excise and I will ablate. This is what it would look like. This is a different lesion and I did not have a post-op lesion. This is what it looks like after we excise. This is more down in the cul-de-sac. What you are looking at in terms - there is an arch here, you can kind of almost see the St. Louis Arch, those are her uterosacral ligaments and we are now down right on top of her vagina. That is kind of one of the typical lesion areas that you will see in adolescents.
So now if we have done our surgery and we have now diagnosed the disease I would like to get at least five years out before their next surgery if not longer. We want to consider the age of the patient, the severity of her symptoms, the side effects of medication we might be prescribing, how much disease we had. We are more likely to use Lupron if there was a lot of disease and we felt like we could not get it all. Sometimes it looks like what we call petechiae, it just looks like somebody put very tiny little dots everywhere across the pelvis. We are not necessarily going to be able to strip out every single little dot so we are more likely to use some follow up Lupron. We want to limit the progression of the disease. There is pretty good work suggesting that medical therapy limits the progression of the disease and we want to achieve pain control.
Medical therapy is after endometriosis has been confirmed. The FDA has approved Lupron. They have approved Norethindrone, which is Aygestin, you can use it anywhere. It comes in 5 mg tablets. You can use it from 5 to 15 mg daily. So, one to three tablets although we are careful the more - we get some metabolic issues, some insulin resistance I think as you move up that scale. And then Danazol is rarely used in teenagers but has been approved. Then we are going to talk about some non-FDA approved therapies.
The mechanism of action for Lupron is that it over stimulates the pituitary and then after about 21 days you have complete suppression. For any nurses that work with patients who might have other issues, like cancer, we work with bone marrow transplant patients in our hospital. We have to be very careful to have them suppressed and have their platelet counts and all that not going to zero right when they are having their flare and about to bleed. There are other situations where we are very aware of this 21 day suppression issue, especially in our pediatric oncology patients. Then usually this should be flat after that and have little in the way of bleeding. We do give add back therapy with Aygestin to protect their bones because the risk of low bone density with this. There are different formulations, the average one is just going to be shot every one to three months. I use the nasal spray in some patients with migraines where we want to go up a little bit slower.
Side effects; again, hot flashes, some complaints, headaches can be a lot if they have a pre-headache history especially, vaginal dryness has not been a big complaint from teenagers. Decreased libido not a very expressed complaint from teenagers. Anxiety - big complaint. Big, big complaint with it and I always warn them this is something they have to think through carefully. If we have a lot of endo we just have to chug through it and they know they have endo and they just chug through it. They do not have the diagnosis yet and they are 18 and they are choosing it instead of surgery, it a part of the counselling. And then we need to think about bones.
Add back therapy is very important it will stabilize the bone density. It helps them with a lot of their symptoms. Sometimes they will stay on add back therapy even after the Lupron is gone because Aygestin alone can be a good treatment. Vitamin D; there is a lot of focus on making sure everybody's vitamin D level is good during treatment. These are just some slides to remind you that if it is low you can treat with 50,000 IU once per week, sometimes easier for compliance but keep their D levels up good while you are working on these therapies.
Norethindrone alone is an anti-estrogen effect and I think again we may find out later it is an anti-inflammatory. That work is all in preterm labor. This is how you can use the tablets. These are the side effects but I think - we did have one girl we were using it for in a different indication. She needed three a day, a Jehovah's Witness who was bleeding and she became diabetic under our watch at the hospital. So you do have to be careful about how you are using it.
Danazol, I am not even going to into this slide but it is there if anybody wants to look at the talk later on. Mechanism of action, side effects, we just do not use it that much in teenagers but it can be very, very effective.
Non-FDA therapies; we have Depo-Provera certainly works but again I have the bone issue concern. Aromatase inhibitors, you do not see it used much in teenagers but does work. And the IUD is really, I think, the new player on the block. Depo-Provera is going to decrease your brain hormones of LHFSH, which is going to prevent your follicle maturation which is going to lower your estrogen levels. It can be given as 150 or 105. They were really hoping the lower dose would help the bones and it does not. That was really sad when they finished the research. It is not any better for the bones and it is more expensive. It is hard to get insurance to pay for the lower dose. The patient might like the idea of having less hormones in her but we cannot statistically say it is going to improve bone density.
Aromatase inhibitors basically help with the expression with the rise in local biosynthesis of estrogen, help inhibit that. We use it in other indications where their ovaries might be independently producing estrogen and their brain is not involved and it blocks the compounding result to estrogen locally in the ovary. It can improve pain scores. You would add it. It needs to have contraception with it because it can cause spontaneous ovulation and bone loss is a risk.
The IUD - the primary mechanism is thinning of the lining and stabilizing the endometrium. It is FDA approved as a contraceptive and it is FDA approved for heavy periods. I should tell you the Mirena is FDA approved for heavy periods, the Skyla is only approved as a contraceptive. It is off label, however, for pain, endometriosis we use it in developmentally delayed adolescents who need help with menstrual hygiene, that might have seizure disorders and we want to use less hormones in them. It is used in utero hyperplasia and they have reversed some uterine cancers in young women who, let's say, have polycystic ovarian disease or overweight and at 19 show up with uterine cancer. They have put an IUD in and have been able to reverse their cancer and keep them from having a hysterectomy.
Pilot studies began in 1999 with endometriosis and the first 20 patients looked good. So they went on and compared them to "let's do your surgery" or "let's do your surgery and put an IUD in". They found they had 75 percent of women who were satisfied compared to 50 percent who had only surgery.
We know that women who have surgery for pain at one year 50 percent will report their pain as back. We know that surgery alone is not going to hold their pain. Levonogesterol compared with the Lupron showed to be equally effective in terms of pain scores and less side effects. The IUD bleeders do have more bleeding. I tell them it is six months, it is a little bit rocky, a little bleeding every day; however, in the end you have four and a half years of not taking a pill every day. Usually they were not doing well on pills when they came to me because we have already tried pills and things should be good and we are really happy - we have got about probably ten girls now out in the community with their IUD post- endometriosis surgery and we are really, really happy with what we are seeing.
The biochemistry of it is just how it compares to Lupron. And again, it has, which is very interesting, we see the red dots, it really has, seems like some anti-inflammatory qualities that the Lupron does not have. I think that is where the IUD advantage is going to be.
So, using it in adolescents - everybody - it is getting more popular but everybody has still be really nervous about using IUDs in adolescents. But the advantages are you do not have to take a pill every day, there is no effect on bone density, which is a huge, huge help. There is no significant effect on your lipids. The disadvantages, the first four months - you have got to really warn them - it is going to be rough, it is going to be bleeding, but they are going to be okay. Pain of insertion; it is always an issue especially with these girls who are already hyped up about pain. They already have a lot of pain issues to begin with and I find that sometimes it kind of triggers that cascade of pain for them. We try to insert them at the time of surgery.
If we go in and say look, "You're not doing well on pills, we think you have endometriosis, when we're there if we see any endometriosis you should have an IUD. If we don't see any endometriosis you should have an IUD because you are not doing well on pills. You should at least switch therapies". So we try to do our surgery for the endometriosis and then put in the IUD at the time of surgery. Paige Hurtwig did a study looking at IUD at the time of surgery or IUD three months later. It takes a little bit longer for the bleeding to resolve if you do the IUD later, excuse me, if you do the IUD at the time of surgery compared to later. But I think the girls would tell you that it is well worth the trade off just to not have the IUD put in in the office, not that they cannot do it. It is a little more painful for them given their history of pain.
Expulsion is there, slightly higher for adolescents and everybody worries about perforation. I am going to show you we have three studies of girls 21 and under, 200 in each study. There were studies across many age groups but they isolated out the 20 and under, there were no perforations. So really, that is a big fear of the mums and it is not really worse. Obviously STDs, there is a risk but just because you are a teenager. I am not saying it is higher because you are wearing an IUD.
This was one study looking at menarche to 21 receiving IUDs. These were some of the complaints; 21 percent wanted it removed. Those were usually girls under 18. We have been a lot more - our endometriosis patients have been a lot more motivated to keep it in because they already were...before they had it in so they are more likely to hang in there. Expulsion is a risk, difficulty with insertion and unable to insert, then we will take them to the OR. Infection, these were, again, I think some of these were STD - yes - about two thirds of these were in a family planning clinic. No perforations.
These are some investigational drugs that going on for endometriosis and Botox they are looking at as well. We are looking at, because you get a lot of muscle spasm when you have endometriosis so we sent our girls onto physical therapy afterwards. And Botox is in a clinical trial at the FDA for some of that muscle spasm.
Hormonal therapy is really I think a very important component. I do not want to operate on a girl and say, "let's see what happens next". I really want to operate on her, get the endometriosis out and get her on something. I really try to encourage families that I think the IUD is their best option given that they almost always have been on pills prior to us going in for surgery. You want to weigh out their age. My ten year old, I did not want to put her on hormones, I put her on Lupron instead and then she had a horrible migraine. We just said we will just see how it goes. You have got to factor in age, especially with the adolescents and the impact on bone density.
The Cochrane Review has demonstrated that women are five times more likely to benefit from surgical management. I think we all agree that surgery is a really, really important component of therapy. The risk of recurrent lifelong disease is high, especially in the adolescent group. We know now that combined surgery and medicine in this German study that came up this past summer, which I do not have on a slide, a 150 in each arm. We could never do this study in the United States. They actually re-laparascoped like 400 women a second time and compared them to medical therapy, surgery therapy or a combination. The least amount of lesions were in the combination therapy group. We really want to put in that.
Each young woman has her own unique history, her own unique findings. We have one girl who is 300 pounds, we could not even take it out because the weight was so intense that we could not move our instruments and she is now been on Lupron continuously for a year and is now having bariatric surgery. I re-biopsied her with the bariatric surgeon when he went in to do her stomach sleeve and her lesions were down by about 75 percent with just the Lupron. I took out more lesions and I told her when she loses 100 pounds I will go back in and take out more lesions. She was a really unique case, kind of doing it in steps off kilter and she was 18 when we made her first diagnosis. It was everywhere. It was like sludge on her colon. Now it down to like little pinpoint areas and we did not even touch the colon. Everybody is unique and concerns need to be considered to optimize medical therapy for that girl.
I can take a few questions if anybody has them. Yes?
Audience Member: I am curious about the Von Willebrands that you said...[unclear]
Dr. Regard: Well we just have patients with it. We have a hematology clinic so it is not that it is necessarily, but it is tricky. We had a couple with Von Willebrands and endometriosis and sometimes they had like irregular bleeding, so that was - and then they would have pain. It took us a while - we have one girl who had seen her adult gynecologist who was like, "Oh, you have breakthrough bleeding on pills, you know, menstrual pain, you have menstrual pain". Finally she switched into my practice at about 15 after a year of being told by the adult gynecologist that is just what happens on pills. It took me a while to put it together but she had Von Willebrands disease so that is why her pills were not really working that well for her. And she had endometriosis. It took us a while to finally get to a scope but she had endometriosis. She had seen GI doctors and adult gynecologists and there was a lot of - but it just kind of took us sort of pulling it all apart. But mostly because we have a hematology clinic that we see more girls with Von Willebrands, it is one percent of the population. So it is there much more than people realize. Yes?
Audience Member: [unclear]
Dr. Regard: I have it with me. I am thinking, I have got it with me and thinking they used excision but you I have got to look. I can look in the method section if they tell you, probably combination. But it is the first study. We will never it done in the United States where they had three 150 in each arm and they relaparascoped like 80 percent of these women at six months, which is quite extraordinary.
Other questions? Okay.