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Hormonal Management, Non-Surgical & Pharmaceutical Approaches - Drorit Or, MD

Hormonal Management, Non-Surgical & Pharmaceutical Approaches - Drorit Or, MD

Endometriosis 2023:
Global Patient Symposium
Together for Tomorrow
March 18-19, 2023 - Einhorn Auditorium, Lenox Hill Hospital, NYC

Hi, I am jut Orr. I am a, uh, fellowship trained, minimally invasive surgeon. I am also, like you said, in NA's, uh, uh, physician, uh, which means I take care of, uh, women in menopause. And what I'm gonna do today is I'm gonna talk to you about the medical management, uh, of endometriosis. So when we talk about endometriosis, we know that about 10 to 15% of, uh, women in their, uh, um, fertil period, which is when you get your periods, have, uh, suffered from endometriosis. And, uh, it's very important to address this subject because a lot of times it's under talked, it's talked, uh, to as if, uh, oh, you have pain with your periods, you should have pain with your periods. That's how everyone is. And no, that's not the case. So I'm sure, as most of you know, endometriosis means that there are implants, um, outside of the uterus, um, that are endometrial, meaning tissue from the inside of the cavity of the uterus gets implanted elsewhere, be it in the pelvic wall, be it in the, in other organs like bowel, like bladder, or in further areas like diaphragm or even, uh, uh, the lung itself.

And the important thing to know is that the official recommendation for treatment with endometriosis would be first line medications in order to decrease the amounts of surgeries that patient have, has to decrease the, uh, uh, to increase, actually to increase the timeframe, uh, from the diagnosis to the first surgery, and try to prevent, uh, going through surgery every few years. So, uh, when we talk about, uh, medical treatment of endometriosis, uh, you know, I divided it into three parts. The first part is talking about medical treatment, uh, in women with suspected endometriosis, but they don't have history of surgery. So they were diagnosed either because of, uh, symptoms that are suspicious or symptoms and things like, uh, ultrasound or an MRI of the pelvis. And we treat them based just on these findings. Then comes the medical treatment of, uh, endometriosis patients after they had surgery, and they were diagnosed with endometriosis, uh, with tissue biopsies.

And then I wanna touch a little bit, uh, um, about the treatment, uh, for, uh, menopausal symptoms, uh, for patients who had surgery to remove their ovaries if, uh, medical management or other surgical ma surgical management failed, um, in the past. Um, this also qualifies, by the way, for women who are treated with specific medications that can cause menopausal symptoms. Uh, but it's mostly for women who really are menopausal because of removal of the ovaries. So why do we even start just with medical management and not go directly to surgery? Few reasons. First of all, of course, it's to avoid the risks of surgery. Any surgery that we do increases the risk for, uh, damage to any intraabdominal organ, be it bowel, bladder, and other organs that are there. Second, it's, uh, decreasing the risk, um, of tissue for scar tissue formation, uh, in the pelvis.

Now, endometriosis patients in general may have scar tissue because of the endometriosis lesions, uh, but the further away we can get from surgery, the less likely that our, uh, surgical intervention will cause even worse, uh, formation of scar tissue. And third, medical management treats the microscopic lesions, which, uh, a surgeon cannot see with their eyes. No matter how talented your surgeon is, and I know a lot of excellent endometriosis surgeons, they cannot see microscopic lesions. And so medical management can address these types of lesions. The downsides of medical management, which is also something that is, that is important to talk about, um, are that first of all, every medication has side effects. We can't ignore that, and we can't, uh, uh, treat it as if it's not true. Um, there can be returned of pain once the treatment is stopped. And for many patients, this is the case.

They will have, uh, pain again when the medication is stopped. Um, it does not affect scar tissue that may be caused by the endometriosis, uh, lesions. It doesn't treat blockage of organs such as, uh, bowel blockage or ure blockage, um, because it doesn't affect the implant size, uh, for the majority of the cases. And, uh, it doesn't improve, uh, lesions within the ovary. Uh, those are cysts that are endometriosis called endometriosis. It doesn't improve fertility. Um, and many medications will prevent pregnancy. And for women whose goal, um, is to, uh, get pregnant, it's important to understand that it will, uh, it, it will prevent pregnancy. Now, I just wanna a side note. I am using the word women. Um, I understand that not everyone with a uterus or, um, with endometriosis identifies as a woman just for the purpose of the flow of this presentation.

That's the term that I'm using. Um, so medical management options include, uh, several families of medications starting with, uh, non-steroidal anti-inflammatory drugs, combination, hormonal contraception, sometimes progesterone, hormonal contraception and progesterone that is not used as contraception. Um, generate analogs, um, danazol, aromatase inhibitors and other things. I'll touch each and every one of these. So, you know, when you look at all these medications, you say, okay, so what should I do? What's the best thing for me? And there is no right answer because none of these medications have been shown to be better than the other medication that you may use. So at, you know, when we come to talk about medical management, the treatment decision really should be individualized. Uh, and it's a shared decision making between the patient and her physician. And should address, uh, factors like pain, fertility goals, uh, um, things like, uh, the severity of symptoms, if there are masses in the, uh, pelvis, if there are masses that call ob cause obstruction in this serv in the pelvis, uh, the extent the location of the disease, uh, the patient's age, um, and medication side effects.

Um, so I'm gonna start with NSAIDs. NSAIDs are nonsteroidal anti-inflammatory drugs. The most popular or well known one is ibuprofen. It's a lot of times over the counter, and it is very easy to use. The benefit of, uh, this group of medications is that it is inexpensive. It is very easy to dose and use, and it is, uh, readily available. Like I said, sometimes over the counter, the, uh, these medications, there's plenty of them. Um, and if one doesn't work, we can choose another. Not all of them work in exactly the same way. There are subfamilies in this group of medications. So if one thing doesn't work, we can try something else. And this would be the first line, our first choice of medications. And this is true, especially for, uh, teenage girls who start menstruating and start having severe pain with menstruation. Um, the recommendation is to start on the first day of the period, um, and do it for one to three days or for the full duration of the pain.

Uh, with the exception of if you have severe pain, you can, uh, start it one or two days before the anticipated menstrual, uh, time. And then you can use it again, either for one to three days into your period or for the full duration of the period. Depending on how much pain you have, they can be used alone, um, in women who want pregnancy. The only thing I will say about that is that there is a subgroup in this, uh, group of medications called, uh, selective COX inhibitors that can delay ovulation. So if you are looking to get pregnant, you may not want to use that specific subgroup of, uh, uh, pain, uh, relievers. Hormonal contraceptives are usually also a first line treatment to use, uh, with combina in combination with, uh, um, the NSAIDs. Uh, they can be combination hormonal contraception, which means they have estrogen and progesterone, or they can be progesterone only contraception.

And so combination hormonal contraception can come in the form of a pill, a vaginal ring, a patch. Um, it can be used long term. Um, it is relatively inexpensive. It's easy to use. Um, it, uh, it's, uh, it decreases the risk for uterine and ovarian cancer in the long term. Um, and it's, it's very popular as a first line medication because of all these benefits. Uh, there is no one contraceptive that is preferred over another. But we do want to start with doses of estrogen in the combination 20 micrograms of estrogen and not the higher doses of estrogen in the combination contraception. You can take them technically cyclically or continuously, but in case of endometriosis, the recommendation is to take them continuously in order to prevent menstruation. Because if you prevent menstruation, at least for some of our patients, it'll prevent the pain that comes with the menstruation.

We do have, uh, you know, patients who have also pain, uh, that is unrelated to menstruation because of endometriosis, so that's not gonna change that pain. Um, but it will decrease the pain if you don't get your period, you have less pain. Um, it also helps with pain that is caused by what we call rectal vaginal endometriosis, which is a, uh, implants that are between the rectum and the vagina and can cause significant pain and can cause significant symptoms in terms of painful bowel movements, et cetera. Um, the, it's really unclear if the combination contraception, uh, can cause regression of the implants, probably not. Um, and there are risks to these medications, just like any other medication, there's risk for clots because of the estrogen component of the medication, and there's risk of recurrent pain once we stop these medications. And the other considerations to take, um, are that these medications cannot be given to people who have high blood pressure.

Um, even if it's controlled, high blood pressure, they cannot be given to women with migraines, with aura. Um, and they really have to be used carefully in, uh, patients who have liver disease, for example. So the combination contraceptives are divided into oral con contraception, vaginal rink, and patch. The combination oral contraception is the most popular one to use because there are so many of them. Um, the vaginal rink is very, very effective for things like rectovaginal, pain for sex, uh, pain with sex, um, and for pelvic pain that is not necessarily re related to periods, and it can be used also in a continuous fashion. Um, in terms of follow up, once we start these medications, the initial follow up would be three months, four months after we start the treatment. You know, when I treat my patients with endometriosis, with, uh, um, medic medical management, the one thing I make sure that I tell them is that it's not a magic trick.

It's not like I'm gonna give you a medication the next day. You're gonna feel better. It takes time, it takes effort, it takes patience. And so it's really important to have this talk with your patients before you start, um, medical, uh, treatment, so that they'll understand that really takes up to three months to feel better with these medications, and they have to accept that and understand that. Otherwise, this is not a great option for them. Um, like I said, we continue the medication in a continuous fashion. We do it either until the patient desires a pregnancy or if they don't desire a pregnancy until the average age of menopause in the United States, which is 50. Um, they, um, if after three to four months the patients don't have enough improvement or they don't have improvement at all, then we would change either to a different type of contraception.

And different type of contraception means a different type of progesterone because almost all these medications have the same type of estrogen with one or two exceptions. Um, but most of them will have different progesterones in them. And so we would change to a different progesterone, uh, in the contraceptives, or we can change to a progesterone only medication, whether it's a, uh, contraceptive or a non contraceptive progesterone. So this is just a table that I put out there because I think it's important to understand this is only a partial list of all the things, all the combination hormonal contraceptives that are available. This is not the full list. It's like half of it. Um, so there are a lot of options out there for us to, to choose from. And, um, I think this kind of puts in perspective how much, how many options there are.

If we talk about progesterone, only progesterone, um, what it does is it stops the growth of endometrial uh, tissue. It causes atrophy or degeneration of the tissue, and that's the mechanism by which it works. Um, it also decreases the risk of formation of clots. So it's safer to use than combination contraception. Um, on that end, um, it's relatively inexpensive and we do see improvement in disease, uh, that is rectovaginal endometriosis, and it can be used in patients who cannot, uh, because of the reasons that I said before or will not use, um, estrogen containing contraceptive options. The problem with progesterone only is that it's had, it has quite a share of side effects. Um, it can have irregular bleeding, especially with the initiation of medication. It can take three to six months for the body to adjust to progesterone only. So you can see irregular bleeding and spotting.

You can see weight gain, headaches, nausea, mood changes, uh, breast tenderness, um, negative cholesterol effects. And in specific, um, um, medications that are given as an injection, it can also, uh, show bone loss. Um, the one thing I will say about weight gain is, and this is something that I tell my patients, um, the medications that we give have no calories, but they do make you hungrier sometimes. And if you keep that in mind and you remember that and you don't overeat, you may be able to not gain weight with them. Uh, because, you know, a lot of times we hear patients saying, oh, I took the pill and I gained a lot of weight. Yes, it can happen, but mostly because you become hungrier and you don't pay attention and you eat more, you increase your intake. At the end of the day, what we eat is what we weigh, uh, said to say for myself also. But, uh,

Um, so when we talk about the contraceptive options in progesterone, um, there is the North syndrome, uh, pill. It's a, uh, dose of 0.35 milligrams per day, and it's taken every day continuously without a stop. Then there are the injection, injection, um, medications, the hydroxy hydroxy progesterone acetate. It can be given as an injection into the muscle, or it can be given as an injection under the skin, and it's done every three months. This is the medication that we see most significantly associated with bone loss. So a lot of times you'll hear or read that they shouldn't be used more than two years. They can be used more than two years, but carefully. And you know, with monitoring, the non contraceptive medications are neuro acetate. The dosing ranges between two and a half milligrams and all the way to 15 milligrams. One, two and a half milligrams is considered low dose, but anything five milligrams and above is considered high dose.

Um, and then you can do the medroxyprogesterone acetate orally, uh, anywhere between 10 and a hundred milligrams. There is no real guideline to tell us what's the right dose. Um, in teenagers, usually the range 30 to 50 milligrams. I'll be honest with you, I hardly ever use these. Um, I think I have many, many other better options than this. Um, I am bringing ologist, um, up because I think it's important to know about this. So this is a medication that as a gist, progesterone only medication is not available in the United States. Unfortunately, it is part of a combination contraceptive that is here, but, um, it's not, uh, a, as a Dion J two milligram pill, you can't buy it here. The, this medication specifically has a lot of benefits. It, um, has, uh, significant, uh, pain improvement profile, um, significant rectal vaginal disease regression. And the main thing that is interesting about this medication is that it's the only one that has been shown to actually cause endometrial endometriosis to shrink.

After six months that you use them, it can shrink by 50%, and after one year that you use this medication, it can shrink by 75 by 75%. Um, unfortunately, FDA does not approve this medication at this point. The only way you can find it is in, um, a, uh, specific, uh, contraceptive called natas. And the problem with that contraceptive is that it's multiphasic, meaning you get different, um, amount of hormones in different times of the month. So it's not a steady state amount of hormones, which is what we would prefer for endometriosis patients. So, um, other options for progesterones are the implant. The implant goes under the skin in the arm, and it stays there for three years. Um, and then the i u d progesterone, um, and that's 52 milligrams of progesterone in an I U D over five years. Those IUDs are approved for eight years for prevention of pregnancy.

But in terms of, um, um, endometriosis pain control, uh, we would do them for five years. And not more than that because that's what is, has been studies. These are not f d a officially approved medications for endometriosis. So these are what we would call off-label, uh, medications. Um, the I U D actually does a great job at local control of the disease at, um, um, decreasing rectovaginal pain, decreasing pain with sex. Um, but again, it's, um, off-label. Next group is generate analogs. So generate analogs work on suppressing a gland that, uh, is in the brain. It's called the pituitary gland. And this gland, um, produces hormones that affect the ovaries that then produce estrogen. So when we stop the, uh, brain gland from manufacturing those hormones that affect the ovary, we essentially decrease the estrogen levels in the body to the menopausal level. Um, it takes anywhere between three to eight weeks to do that.

Um, but we do see with these medications, regression of endometriosis, uh, um, you know, symptoms, pain and lesions as well. Um, the problem with this medication group is that it has a lot of side effects, especially, uh, things like menopausal side effects, hot flashes, night sweats, sleep disturbances, vaginal dryness, pain with intercourse because of the vaginal dryness. Um, and it does entail decreased bone density, um, and increased cholesterol with it. Um, in terms of, um, other things that can happen, you know, they did studies on these medications because they're also used for prostate cancer in men. And they said, oh, it can increase heart attacks, diabetes, this and that, when we talk about prostate cancer. And we're talking about older men, um, who are treated for cancer. So it's completely different for younger women or females, um, in who are treated with these medications. These risk factors probably don't apply.

So that's just, um, if you read anything about that. Um, there are two types of medications or subgroups of medications. Um, one is the general H agonists. They are built, um, they're synthetic, but they're built the same way that the, um, inherent or what we produce in the body, uh, substance, um, is, uh, is they're built the same way. So what we see in these medications is with then we, when we just start doing them, um, you have an interval of up to 14 days where you'll have increased pain, um, increased symptoms with endometriosis, because what they do is they attach to the, the gland in the brain, and they cause excess estrogen initially because they make it work harder. But then because of the continuous attachment to the brain and the brain doesn't get a break from it, what it does is it stops working on it, kind of like a desensitization of the brain, and then the estrogen goes down.

So that's a consideration to have that you're probably not gonna be improved within the first 14 days, but it's gonna take longer than that. Um, 75% of women, um, will have menopausal levels of estrogen within three to four weeks, and 98% will have menopausal levels of estrogen within eight weeks. Once we stop these medications, it takes two to three months, uh, for, um, your periods to come back, but they do come back. Um, and the me these medications are limited for use between six months and one year officially, um, because of the bone, uh, side effects, especially, there are some leeways to talk about, but the official recommendation is up to one year with something called aback therapy, which I'll touch in a bit. So the types of medications that we have are Lupron, which is an injectable medication. It's used either once a month or once every three months, depending on the dose.

Um, there is a SY grail, which is a, uh, inhaled spray, um, that is used on a daily basis. And then there is the ZO Dex, which is, again, an injection, but that's an injection under the skin, and that's used every four weeks. And those are the three FDA approved medications for endometriosis. Aback therapy is hormonal therapy that we give for women, um, with these, uh, treatments in order to prevent bone loss. So the advac therapy is essentially what we would use for women who are menopausal. It's the same dosage, it's not the dosage of the combination contraception, usually it's given in lower dosages, which is what we would use in our menopausal population. Um, the current recommendation is to start add-back therapy with the initiation of these medications. Not to wait a week, not to wake a, not to wait a month to start them together.

It doesn't change the, um, quickness of how fast the medication will affect you, uh, but it will prevent you from having severe side effects, even things like hot flashes or vaginal dryness. So it's important to start them together, and it is protective for the bone, which is why we actually do it. Um, so edic medications, the one FDA approved medication is a neurotin acetate at a dose of five milligrams daily, and it's approved to use up to one year. However, not everyone can tolerate the side effects of neuro acetate, higher doses, which is bloating and abdominal discomfort and kind of weight gain and feeling unwell. And so sometimes we will choose either not to start it all with this or to, uh, change it to something different, um, if, uh, the patient cannot tolerate the side effects. So you see there is a, a, uh, bunch of options in terms of, uh, the, um, medications that we can use.

They're usually combination of low dose estrogen and, uh, some form of progesterone. I just wanna point out which one is it? One, two, the third one. The third one, the conjugated estrogen 0.625 with the North Endone is the only one that has the full effect, um, on the bone. That is beneficial. The other ones have some beneficial effect on the bone, but it's not as good as, uh, um, if you're not on these medications or if you're on the North Endone acetate. Um, and it can come in several forms in form of a pill, a patch, um, you know, it's, uh, it's variable depending on what's comfortable, uh, for the patient to use. The other consideration is that there are options for vaginal symptoms to use. Um, micro doses of estrogen in the vagina, those are completely safe. They don't increase the pain with endometriosis. The doses are so low that when you put them in the vagina, almost nothing gets absorbed into the system. Doesn't increase the levels of estrogen in the blood. And, uh, they are very helpful, uh, for vaginal symptoms.

What does add back?

Add back means that we're adding what's missing from the, uh, from the body, meaning if the estrogen goes very low, um, and the, what we do is we give back something in order to, um, assist the body to, uh, deal with the symptoms, whether it's vasomotor symptoms or the main goal is to do, um, protection of the bone with these medications, but it also helps with the symptoms of, of, um, menopause. Um, so alternatives to these medications are, uh, either to decrease, uh, the dose of daily medication with a spray or increase the interval between, uh, medication, uh, administration if we do the injectable medications. Um, and we can also treat symptoms with, uh, non-hormonal options if hormones are not an option. But in those, I'll talk about actually a little bit later when I talk about menopause. So they all are all valid for this as well.

Generation antagonists are the other subgroup in this, uh, big group of medications. The benefit of them is that they immediately, uh, block the function of the pituitary gland, and so they work immediately. You don't have those 14 days where you may have exacerbation of symptoms. Um, they're easier to use, they're in the form of a pill. Um, they're relatively new medications, so there's a little bit less research on them. Um, but the other benefit that they have is that for women who actually require, um, addictive medica pain medications, it decreases the use of these medications for this group. So the two, um, options for us are either, uh, or Alyssa, or my Fbri or Alyssa, is given at a, uh, lower dose once daily that can be used for two years for women with moderate endometriosis pain. Or it can be given as a high dose medication, 200 milligrams twice daily, that's limited for six months use.

Um, and that's used specifically for patients who also have severe pain with, um, um, sex. The, the, this medication does not come with an add back, but technically you can do an add back to this medication. Um, it's not contraindicated to do add back to this medication. And so if you do add back, you may even extend these medications, especially the six month, uh, um, option to a bit longer period of time. Um, my fbri is a relic that comes already with estradiol and no syndrome in the tablet. And so th those dosages that you see, there are dosages of what a menopausal woman would take to control her, um, hor her menopausal symptoms. Um, so we're not using high doses of estrogen, high doses of, uh, progesterone. It's the normal doses that we would use for any menopausal patient. Um, and that's approved for two years.

Next group is aromatase inhibitors. This is an interesting group. This is a group that we never, ever, ever start as a first line of treatment with because it has a very, very significant effect on the bone. Um, it is an off-label indication, and what it does is it decreases estrogen essentially everywhere. So most of the estrogen in, uh, a female will be produced in the ovary, but there is some production in the brain and there is some production in the fatty tissue. Um, this medication will stop the conversion in the fatty tissue. It will stop the manufacture in the brain. It essentially decreases estrogen to very, very low doses, but it has significant effect on the bone. It causes a significant, uh, uh, bone loss. So these medications are never chosen as a first line. Um, and they should always be given with a g nrh, um, analog or a combination contraception or a progesterone only, or Gen r H and, uh, one of the other two. And the reason it's given with these, uh, combinations is because if we don't give, um, theus inhibitors with something else, you can have formation of significant cys on the ovaries, which we're trying to avoid.

In terms of the medications, there's two types of medications, anastrozole and, uh, letrozole. They're both dosed once daily. Um, and then the next thing that I wanna talk about is danzo. Danzo is a standout medication. It's separate. Um, it's an androgenic medication, um, and, uh, it works really well on endometriosis, decreases pain. Decre, um, causes reg regression of lesions has a lot of benefits. The problem is, is that it has a lot of androgenic side effects. Your hair can grow, you get acne, you can gain weight, uh, you can get muscle cramps. Uh, your voice can be deepened, and that's the voice depending, is not reversible, by the way. So there's a lot of side effects that come with this medication. This is why it's not commonly used. I will say that for the transgender population, this is actually a great choice, uh, if they have endometriosis because it has the benefits of the androgenic properties and the decreased pain with endometriosis.

But that's the, uh, uh, subgroup that will benefit most of from these medications from the ole. Um, otherwise it wouldn't be my first, my first or second choice to use. Um, and the dosages are, um, anywhere for mild pain, anywhere between two to 400, um, milligrams per day. Um, and for severe pain, it's 800 milligrams per day. With the understanding that the, uh, side effects are dose-dependent, meaning the more you take, the higher the dose, the more symptoms you may encounter. There is an option to do vaginal danil at a lower dose. That's a compounded, uh, um, medication. It's not, you can't buy it as a prescribed medication, uh, when you go to the regular pharmacy. Um, and, and it seems like it really helps with, um, pain with, uh, um, sex and with some of the, um, menopausal, uh, symptoms in some of the, um, um, endometriosis symptoms.

It's more local and it has less side effects in terms of what the doole, uh, if you take it to stem acute will have. In terms of non-hormonal medications, there are medications that we, uh, use for neuropathic pain, uh, in patients who had surgery or who had not had surgery, but have pain that is not relieved by the medications. There is a, uh, a cannabis option that I'll talk in a second. And ulu ulu is actually interesting. It's a new, um, compound that is studied. It's not a new compound, it's a new thing that we're studying. It's actually a, uh, a, um, olive leaf extract, like from the, from an olive tree, and it's sold over the counter as an antioxidant, anti-cancer, anti-everything. Um, there's one study that looks at this, uh, um, compound. What they did was they caused endometriosis in mice, and then they treated them with this extract.

And what it shows is regression in endometriosis, regression in symptoms of endometriosis. That was very, very significant, um, without affecting fertility. So you can take it and still preserve your fertility. So I don't know where this is going to lead us more to come, but this is, this may be the new thing, uh, for endometriosis. Um, and then cannabis is, uh, something that I have studied. Um, the research goes both ways. Some, some say that it's great, some say it's horrible. The problem with cannabis is that it is, um, um, something that will decrease fertility for women who desire fertility. It decreases the egg quality and it has the potential for, um, um, addictive, uh, um, use. And so at, uh, at the, at the time being, it's not recommended to use for, uh, control of pain with endometriosis, I will say that in 2020, they started this study that is supposed to be finished around the end of 2024 that looks at use of cannabis with endometriosis.

So I don't know what that's gonna bring, but, uh, we'll wait and see, um, if they, um, if they find that it, it may be helpful for at least subgroups of, uh, endometriosis patients. Neuro neuropathic pain medications, uh, can be anti-seizure medications, tri cyclic antidepressants, Tramadol, which is a, uh, weak, um, opioid or strong opioids. The last two we try not to use with endometriosis patients if only possible. So the anti-seizure medications can be either gabapentin given, uh, uh, one to three times a day, um, or, uh, pregabalin. Those are started in a lower dose and gradually increased up to the point where they will prevent, uh, the neuropathic pain. Um, and the other options are tricyclic antidepressants. The problem with this group of medications is that it causes, uh, um, people to be very sedated, and so it should be used at bedtime, and a lot of women don't wanna use it because of their sedative effect that they have.

And then, like I said, um, any type of opioid we try to avoid unless we really have to use it, um, because of the, um, uh, potential addiction to it. And if we do have to use it, we should use it as at the lowest dose possible, uh, to control the pain. Um, in terms of contra complimentary therapies, acupuncture, diet, herbal, uh, uh, medications, pelvic floor, uh, physical therapy, acupuncture, I did, uh, see one article that talked about the fact that, um, acupuncture around the ear, uh, can actually help with pain with endometriosis, and that was compared to other placebo and other, uh, um, options. Uh, but there is no diet goes through the previous lecture that shows that if you adhere by it, your endometriosis will get better or worse. Um, herbal medications don't really, um, have any effect, uh, that we can establish in terms of research on endometriosis.

Um, pelvic floor, physical, physical therapy, however, is, um, something that we do use a lot, because a lot of times what happens is with endometriosis comes high flo, high pelvic floor, uh, tous because of the pain. So it's kind of like a vicious circle. You have pain, you try to have sex, it makes the pain worse. You contract your muscles, you try to have sex again, it's worse. You, you contract your muscles even more. And so it's kind of like a vicious circle that you can't get rid of. And pelvic floor physical therapy can really help with that, uh, and can really improve, uh, pain, um, with sex in, uh, in endometriosis patients. So in terms of medical treatment after surgery, so why do we even treat? We treat because if we don't give medical management after surgery, a lot of times we'll see recurrence.

We see recurrence up to 21.5% after two years, and almost up to 50% after five years. So we do wanna give medications, hormonal medications, at least six to 24 months after the surgery. Um, the treatment options are essentially everything that I said until now. Everything can be used. Um, and the decision really is based on your conversation with your physician and your surgeon. Um, and then comes the other part of the talk about menopausal symptoms. So, um, the recommendation, uh, for women with menopausal symptoms, um, and because of, um, removal of the ovaries is to be treated, the treatment goals is one, to control the symptoms, and two, to help with bone health, cardiac health, brain health, it helps with everything. Um, you know, the measurement can be non-hormonal, um, and hormonal with younger women. I personally prefer hormonal medications because of the benefits of the really heart disease, uh, decrease, uh, bone health, uh, increase, et cetera.

So, you know, menopausal concerns can be anything from hot flashes to vaginal dryness, to decreased libido, um, all the way to mood changes and, and et cetera. You see, and the treatment after surgical menopause can be divided into hormonal treatment, non-hormonal treatment, treatment of decreased, uh, uh, um, desire to have sex, a decreased libido, um, and vaginal treatment for, uh, vaginal symptoms. So this is kind of like a chart, a flow chart of what the options are, be it, um, um, you know, behavioral changes, non-hormonal medications and hormonal medications. And this is a ti table that NAMS actually published that shows what is recommended based on their research. Um, and what is may be recommended, what is not recommended. So you see that there are medications that are not hormonal that can be, uh, effective with, um, with, um, hormonal, um, like with menopause. And there are some things that are not clear yet.

Uh, for example, weight loss is unclear, um, acupuncture is unclear, et cetera. So for non-hormonal medications, the only FDA-approved medication is peroxetine. Um, the other SSRIs there are, um, off-label, but they do help with menopausal symptoms should we choose to use them. Um, you know, other options for off-label medications are gabapentin and clonidine. Gabapentin, um, has the benefit that it helps also, the neuropathic pain, clonidine I never use. Um, it has a lot of side effects. Um, it's not as effective as other non-hormonal medications that we, uh, use. And so I, I never use it. Um, in terms of hormonal therapy that we can use, we talk about estrogen therapy, about combination, estrogen, progesterone, and progesterone only therapy. The point I want to make in this slide is estrogen therapy technically can be used alone for women with menopausal symptoms without a uterus, and it should be technically used alone for women without a uterus.

But with endometriosis patients, because of the lesions, it may be microscopic and still in the pelvis changes the picture a little bit. And so we may decide even though you don't have a uterus, that the good option for you is to still be on combination, estrogen and progesterone. Because if we only use estrogen, it can exacerbate the pain of the endometriosis lesions. So the preparation types can be transdermal oral or vaginal ring. And there's a bunch of types of, um, estrogens that are used. Some of them are natural occurring, like the first one, and some of them are synthetic. Um, the estrogen administration can be either in oral tablet, daily, a patch twice weekly, a gel or spray on a daily application, and a vaginal ring that is placed, uh, once every three months. Vaginal rink is very hard to get approved by, uh, insurance.

So that's a lot of times not really an option. Um, in terms of progesterone, progesterone, um, and synthetic progesterones can be used for menopause and can be treatment option for hot flashes. Um, the thing that is FDA approved is something called protium, and that's a, uh, bioidentical hormone. It's used as a micronized progesterone at bedtime. It has a sedative effect. So this is why the recommendation is to do it at bedtime and not, um, first thing in the morning. For example. The significant recommendation with combination hormonal therapy is to do either continuous cyclic or extended cyclic, kind of like what we do with combination con uh, contraception. But again, in the case of women with endometriosis, um, I would do continuous because I don't wanna have those cycles of, uh, time when you would bleed and then you may get pain. Um, the contraindications for hormone therapy are many if you have the uterus but not the ovaries.

You have abnormal bleeding, um, if you have cancer that is sensitive to estrogen, um, et cetera. Um, in terms of bioidentical compounded hormones, the recommendation and I adhere by that recommendation is that if you have a, a prescription option, use the prescription option. These are medications that have minimal regulation over them. They're not accurate in terms of the dosing. Um, and they can sometimes be overdosed significantly or underdosed significantly. And that's something that has to be, uh, considered, um, when we are trying to treat, uh, hormones. Um, and there are many, many compounds there that work well that are government regulated. The only exceptions I will say is if you have, uh, an allergy to the comp components of those, uh, medications that are government regulated, or if you don't, you can't find a dosage that you want, uh, to use. Um, in terms of vaginal symptoms that can occur in menopause, uh, they can occur both because of menopause and because of treatment with medications.

Uh, they induce medical menopause. The main symptoms are vaginal dryness, burning irritation, um, and pain with intercourse because of the dryness. So there are behavioral treatment options, non-hormonal treatment options and hormonal treatment options. Um, you know, the behavioral and non-hormonal are divided into a pelvic pelvic floor pt, which is helps greatly with this, uh, um, type of problem. Um, vaginal dilation with dilators, you can buy them on Amazon event today. Um, and regular sexual activity. And then over the counter we have to consider vaginal moisturizers and as well as lubricants. When moisturizers are a maintenance type of, uh, treatment, meaning you do it three times a week every week, not stopping. Um, and lubricants are used for intercourse. Uh, you have water based, you have, uh, silicone based. I prefer the silicone based. They have a nicer pH profile on the vagina. They feel nice.

And today you can use them even with condoms, um, which in the past you couldn't. So, um, unproven or ineffective therapies, according to studies have been hyaluronic acid and herbal products. Uh, there is no study that shows that, uh, there is an improvement in symptoms in menopause with these types of, uh, medications. Um, in terms of prescription medications for the vagina, you can do vaginal estrogen cream, um, insert, uh, or D H E A insert, um, vaginal estrogen, low ring, a low dose ring, or an oral tablet called Thea. Um, the vaginal estrogens are used, uh, for pain with intercourse for vaginal dryness. Um, and they, like I said before, almost don't get absorbed into the system. And so they are a very, very safe option for, um, any patient who chooses to use it. Even patients with history of, uh, um, hormone responsive cancer, um, they are used.

Uh, so intrarosa is the D HHA insert. It is an insert, uh, that is, uh, made out of a precursor to testosterone, and it's, uh, it gets, uh, disintegrated and becomes testosterone and estrogen in the vagina in the vaginal cells. And it helps both with vaginal dryness, with pain with sex. And according to some studies, increases libido increases, uh, arousal increases enjoyment with sex. So it has some benefits to it. Um, it improves the vaginal pH also of the vagina. The main, uh, side effect that it has is discharge. And then OIN is a once a daily tablet. Um, it's, it's 60 milligrams per day. It helps with vaginal dryness and with pain with sex, and it improves the vaginal pH. Um, but, um, one of the side effects is that it does have some menopausal, uh, symptoms along with it, like hot flashes and night sweats that can be exacerbated for decreased libido.

We're almost at the end, uh, for decreased libido. Uh, the two options are testosterone and the vaginal D H E A, which I just mentioned. Testosterone is not an on-label medication, you know, um, we do know that it improves, uh, um, desire. It improves, uh, arousal improves enjoyment with sex. It improves a lot of things, but because there's no approved, um, medications in the United States for females in female dosages, it's a little bit of a problem as to how to treat. So some providers will, would choose to use, uh, compounded, but there are options that are not compounded. So essentially what we can do is we can take a male, uh, dose and cut it into 10th. Um, if we use, let's say the gel, uh, 1%, um, they take five ccs that has, uh, 50 milligrams. So a female, what she will do is she will take half a cc, which is five milligrams, and then it doesn't have the side effects of testosterone, but it has the benefits of testosterone for women.

So the way that we decide whether we do, um, testosterone treatment is first of all, we have to do, uh, um, blood tests, uh, prior to administration. It won't determine whether we should do testosterone, but it will give us a baseline as to where we're starting and what our goal is. Our goal is for testosterone to be in the premenopausal range, but not higher than that, because higher than that is super physiologic. It's not something that we will benefit from, and we will have side effects from the first blood test that we do once we start testosterone treatment is anywhere between three and six weeks after we start it. And if we need to increase the dose, we can, if the dose is appropriate, we'll do another test in about eight weeks. And after that, if the dose is fine in terms of, uh, the blood level of testosterone, we can do, uh, um, every six months blood test to make sure that we continue, uh, with the, with the dose that is appropriate.

If we don't have improvement within six months of the libido and the symptoms that testosterone is supposed to alleviate, then we should stop it because if there's no improvement, um, with physiological levels, then it's, it's not doing what it's supposed to do and there's no point in, in using it. Um, it's supposed to be used, um, as a, uh, gel and you can apply it to the skin. You can do it in areas that don't come in contact with other people so that you reduce the skin to skin transference. So you can do it in the back of the thigh, the back of the calf, or the side of the thigh, um, or even the va. Um, and you should see improvement anywhere between four and 12 weeks. Um, other testosterone formulations are the palate and the IM injections. Those are not recommended actually to use because you have less control of the dosages that you get from it, and you may have more significant side effects in terms of testosterone.

So those are, uh, um, not really recommended for use. And then, like I said before, vaginal, uh, D H E A is, uh, something that can be used also. Um, when you have decreased sleep below, it increases the satisfaction with sex. And, and non-hormonal medication is bupropion. It's used in an antidepressant, but it also is used to, uh, um, for patients who try to stop smoking, it has a lot of functions and it's used, um, at a dose of 300 milligrams per day, divided into two doses. There are other medications that I'm sure you guys heard of, um, like medications for premenopausal women. The problem with those medications is one that they're approved only for premenopausal women. And two is that the definition of why you should use them is if you don't have a medical issue or you're not taking a medication that is causing your problem. And that's kind of like what we're doing. We're taking a medication or we have a medical problem because of an issue that is causing this. So they're not really a good option, uh, for our population. And that's it.