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Podcast (MP4 40170 kb)

Transcript

Ayman Al-Hendy:

Advances in Therapy, Uterine Fibroids: A Podcast on Patient and Physician Perspectives on Medical Management and a New Medical Therapy (Relugolix Combination Therapy).

I'm Ayman Al-Hendy. I'm a gynecologist and minimally invasive surgeon here at the University of Chicago, and I am a physician scientist with NIH funded research on uterine fibroids for the last 23 years. And I'm just so excited to share this podcast with Sateria. Sateria: you want to introduce yourself, please.

Sateria Venable:

Hello, Sateria Venable here. I am patient turned founder of the Fibroid Foundation. We are based in the DC Metro area, and this year we celebrate our 10th year of advocacy.

Ayman Al-Hendy:

Fantastic. I'll get started. As we all know, fibroids are unfortunately very common, benign tumors of the uterine wall of the myometrium [1,2,3]. Some literature suggests that they can affect up to 70% of women by the age of 50 [4]. So, it's extremely common.

It's a benign disease. It's not cancer, has nothing to do with cancer, which is good news, which means the disease stays in the uterus, doesn't metastasize, doesn't go to any other organs [2, 5]. However, it is really a major driver of poor quality of life for patients who suffer from this disease [2].

They [fibroids] have a negative effect on patients’ quality of life because they can cause a lot of symptoms. The most common symptom is heavy menstrual bleeding [5, 6]. A patient [may] come and complain that “my periods are still regular, but they are extremely heavy,” and they describe this in many different ways, and I'm sure Sateria will comment on that. But also the fibroids can cause irregular bleeding. I have seen patients who no longer actually can recognize when is their period and when is the irregular bleeding, because the bleeding just keeps going on and off.

Fibroid also can cause pelvic discomfort, pelvic pain, congestion [3]; patient says, “I feel that pressure in my pelvis because of my fibroid disease.” Fibroids can make it also difficult for couples to get pregnant and they have been associated with infertility, and also they can cause some urinary symptoms and constipation and GI symptoms (gastrointestinal symptoms) [2, 5,6,7].

But we are talking about the patients–I would love now to get your perspective, Sateria, from the patient point of view about fibroids and how [they] might affect a patient's quality of life.

Sateria Venable:

Certainly, my pleasure. Fibroids can really overtake every aspect of a patient's life. It can touch your work life, your home life, your social life and well-being because you feel very exposed and you are defining all of your activities around whether or not you're on your period, whether or not you're feeling well, and whether or not you're experiencing heavy menstrual bleeding.

I started advocating in this space after my third of fourth fibroid surgeries. And, at that time there was still, and there is today, but there was even more of a stigma around menstruation and around discussing menstruation and menstrual-related topics. And this stigma has dissipated somewhat, thankfully, due to the rise in social media. But there's still a lot of suffering in silence. And in terms of the symptoms that I and other fibroids patients have experienced, they are severe. And I can't emphasize that enough. I've been on an airplane where I had a gush and couldn't get up to change my pad and gushed out all over my clothing. My hemoglobin was low. I was severely anemic for many, many years. And at one point when I was bleeding the heaviest, I could lose up to two points of my hemoglobin in a single day and go through an entire bag of sanitary napkins. And there's an uncertainty with not knowing how severe the symptoms will become. And it can affect a woman's emotional well-being. And it definitely has an impact on relationships.

Sateria Venable:

There's also dyspareunia, which is the actual medical term for pain during intercourse, which is very common. And oftentimes community members reach out to us and they do not realize that it's a frequently common symptom of uterine fibroids. And so, you know, women adjust to these symptoms in Herculean fashion. But, you know, it's my hope through our advocacy work that they won't have to adjust to the symptoms–that we can discover and utilize and communicate and educate on symptoms, on treatment options, rather, that can help them to have a better quality of life.

There are patient advocacy groups, such as the Fibroid Foundation, that provide support systems, and we really try to have a sisterhood of support mechanisms and surgery buddies to walk through this experience together because a patient perspective is a perspective that is unique, it's comprehensive. I believe that every woman is an expert in her own body and that there's tremendous knowledge that can be gleaned from really understanding the patient journey.

So, with that, I'll turn it back over to you, Dr. Al-Hendy, and ask you if you would share the provider perspective on fibroid diagnosis and management.

Ayman Al-Hendy:

Thanks Sateria. I mean, I really love listening to you and thank you for all the work you and Fibroid Foundation are doing on behalf of patients to increase awareness of this. I couldn't agree more about what you said about the normalization and the stigma, which you right away will recognize when we talk about the diagnosis.

So, it's really not difficult to diagnose if a patient has fibroids or not. A simple exam, which is part of any office visit for gynecological assessment. There's something called a bimanual exam where the doctor or the health care provider will assess the size of the uterus. In, you know, in a regular average size patient, it's easy to feel the uterus, and fibroids make the uterus larger and make the contour or the outline of the uterus irregular. So, right away, the health care provider can at least suspect or even diagnose fibroids in the office. But also very easily, very routinely, we use a simple imaging modality. It's called ultrasound, transvaginal ultrasound, which can diagnose fibroids easily. And I tell my patients it's a great tool because it not only tells me if the patient has fibroids or not, it tells me a lot more, tells me how many fibroids, because unfortunately, there is a variation. Some patients will have a single fibroid, others can have many, many fibroids in the same uterus. So, I would say ultrasound is a very good tool. Occasionally we do MRI, which is a more advanced form of imaging, mainly if the patient is going through a surgery (e.g., myomectomy).

So yeah, so that's the diagnosis. Of course, also part of the workup for a patient who is having heavy menstrual bleeding and fibroids, we like to know the general condition of the patient. We like to know her hemoglobin level and also hormonal levels, etc. So, there's usually some blood work that is done. And many times also we like to know the condition of the lining of the uterus, the endometrium, so, we do also endometrial biopsy.

Of course, once you have the diagnosis, then the next question or discussion is the treatment options. And I'm just so excited. Now, in the last couple of years, we have [many] less invasive treatment options. So, we'll have a chance to talk more about that very soon. But generally, the landscape for treatment of fibroids until recently, unfortunately, was mostly tilted towards surgery. And the reason for that is, until recently, we really didn't have high-quality FDA-approved treatment, medical treatment option or nonsurgical treatment option for fibroid. We as gynecologists, of course, improvised and used other treatment options to try to help our patients. But really these medical treatment options were not based on, you know, high-quality, well-designed clinical studies. And they were not FDA approved specifically for fibroids. That's why many of the patients with fibroids ended up usually with surgery. Either in the form of myomectomy, which as we all know, is going in, removing the fibroid and then suturing the wall of the uterus back together [2, 8]. But usually surgery for fibroid, unfortunately, is in the form of hysterectomy [2, 8, 9], which of course, as we know, is going in and removing the whole uterus with the fibroids in it. We are the number one country in the developed world in the number of hysterectomies that we do every year. So, we do a lot of hysterectomies. It's too many, in my opinion. And the reason I'm saying these comments is [because in] any disease in medicine, the way we teach our students and residents and fellows is “let's try simple medical therapy first and only if that fails or there is some restriction (e.g., the patient is not a good candidate for medical therapy), then we go to surgery or more invasive procedures.”

In fibroids, unfortunately, this whole paradigm has been ignored. And I understand because a few years ago we really didn't have good durable medical treatment options based on high-quality research and FDA approval. But that has changed in the last 2 or 3 years. I think this paradigm needs to be revisited and now fibroids should be like any other disease: medical treatment options should be entertained and evaluated and explored and offered first and then only surgery would be the last resort. The other reason I am sharing these comments about hysterectomy is it's not without possible problems. There is high-quality research suggesting that hysterectomy is associated with short-, intermediate-, and long-term complications for the patient [9]. Short, of course, like any surgery, when I talk to my patients, like any surgery there is a chance of something going wrong in the operating room (OR) on the operating table. Things like injury to a blood vessel, infection, injury to other organs like bowel or kidney or ureters and so on. But then intermediate, hysterectomy has been associated with complications such as urinary incontinence.

But really the most important literature that came in the last few years from our team and other groups is the long-term complications of hysterectomy. We looked at the health status of women who had hysterectomy in their 30s and 40s without removing the ovaries. So, they still have ovaries. They didn't go through premature menopause. Then, we looked at their health 20 and 30 years later, and there was increased risk of heart disease, dementia, diabetes and some other serious health complications in women who had the hysterectomy early in life versus those who did not.

So that's why the American College of Obstetricians and Gynecologists, in their most recent guidelines on fibroids in June 2021 [10], said that all of these issues, immediate-, intermediate- and long-term complications of hysterectomy, should be part of the discussion with the patient that's considering hysterectomy. So, however, the good news is there are now medical treatment options for fibroids. I'm so excited about this new family of compounds called oral gonadotropin-releasing hormone (GnRH) antagonist, and we'll have a chance to talk about this in a minute or two.

But before that, I want to go back to you, Sateria. Tell me about the treatment discussion that the patient usually has in the doctor's office from the patient’s side.

Sateria Venable:

Absolutely. So, we really try to frame the discussion based on how the patient’s feeling when they enter the examination room. And oftentimes, they've gotten to a point where the fibroids just have exhausted them, and they've looked at all other options that they could potentially manage on their own. And they've decided to come in for a consultation. And if they've been experiencing heavy menstrual bleeding, they're often sleep deprived from being up (probably hourly or more than that), changing a pad and they're fatigued. And those dynamics put an urgency on finding a solution, which can be a negative thing. It's good that they're there for treatment, but if they're quickly trying to understand what fibroids are, because sometimes, like me, you're hearing the word fibroid for the first time when you're diagnosed and you're not feeling well. And as a very dear physician friend told me: try not to make any decisions, like a surgery, when you're not feeling well.

So, it's important that the patient develops some shared decision-making practices to be able to coordinate care with their provider based on their treatment needs. And that includes utilizing medical therapies to help stabilize the patient prior to considering any procedure that would require surgery. And I think that that really can't be over emphasized: the importance of utilizing shared decision-making and the importance of leveraging the nonsurgical tools that we now have available to us, and I’ve experienced another dynamic which is, I’ve frequently been told, despite the fact that I tell my providers that I'm a patient advocate, that “you're of a certain age, why don't you just have a hysterectomy?” And that's a discussion that I would like us to quickly move away from having and really focus on the patient's goals for treatment, because whether or not the patient has completed their childbearing or doesn't have a goal of childbearing does not mean that they want to lose a body part, that they would like to lose their uterus.

So, walking through those treatment options is very critical, and developing a really customized treatment plan where the provider is really listening to the patient really creates the best outcomes possible.

Ayman Al-Hendy:

Excellent. Excellent. And again, I always find myself 100% agreeing with you, Sateria. But specifically, about that discussion you said the patient would have with the doctor. I am a big fan and a big believer of patient-centered care.

But I would say if the patient has, you know, significant disease, moderate to severe, I think some of this newer FDA-approved medication would be very helpful in those scenarios. I'm just so excited that now we have in the US at least two FDA-approved oral treatment options against fibroids [11, 12]. Today, I want to talk probably more about the relugolix combination therapy. So, relugolix is an oral nonpeptide GnRH antagonist [12]. So, the two unique things about this compound, relugolix, is first it's an oral, because it's a nonpeptide we can take it by mouth or the patient can take it by mouth and it's not going to be destroyed or digested in the GI tract, unlike some of the previous injectable GnRH analogs and so on. Second, they are pure antagonist, so they are GnRH antagonist, not agonist, not analog. What that means is relugolix will go and bind to the GnRH receptor in the anterior pituitary right away and inhibit it right away [12, 13]. And then with that the serum level of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) will go down and the ovary will stop producing estrogen and progesterone [12].

And of course, estrogen and progesterone are the lifeline of fibroids. So, when you deprive the fibroid from those two hormones, they start to shrink and the symptoms related to fibroids start to get better. So, unlike the GnRH analog or agonist we had earlier, there is no flaring effect or no things will get worse before they get better and so on. So that's one of the two very favorable features about this new family of compounds (oral GnRH antagonists). So specifically, about relugolix combination therapy for treatment of heavy menstrual bleeding associated with fibroids. So, we had that now for almost 2 years. And I think it presents a great treatment option for patients with uterine fibroids.

Personally, I think for me, honestly, it's the first line of treatment for uterine fibroid patients because it emerged from a highly rigorous, highly meritorious, long clinical research program [13,14,15]. So, it's based on solid data. It's one tablet, once a day.

So, what's in that tablet of relugolix combination therapy? There are 40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate all together in one tablet the patient should use once a day. So, the research has shown, and also in my real-life experience with relugolix combination therapy, the patient should start using this once they start their period. If you use it later it’s still going to work, if you start in the middle of the cycle, and so on, it will work, but it might take longer to show the beneficial effect. So, the way it works, as I said, is by decreasing serum levels of estrogen and progesterone. So, you're depriving the fibroids from their lifeline. However, because the tablets also contain 1 mg of estrogen, you actually keep the serum estrogen level in the appropriate kind of midfollicular phase range, roughly around 30–60 pg/ml. So, the patient will get the benefit of the fibroids starting to die off and get improvement in heavy menstrual bleeding, but they will avoid the side effects from low estrogen, such as hot flashes [12, 16]. So, it keeps the estrogen in that nice therapeutic window in the middle.

The process to use relugolix combination therapy in your patient with heavy menstrual bleeding is very simple. Typically, I give my patient a prescription for 1 month with 11 refills and ask them to follow up with me after a year. I tell them, if you start using it the first day of your period like we did in the study, then you should expect around 50% decrease in your menstrual bleeding already within the next cycle [13, 14]. And if you stay on it, then you should expect 90% decrease. So, significant, dramatic decrease in menstrual blood loss. And many patients actually stop having periods altogether. They have amenorrhea. About 70% of patients on relugolix combination therapy had amenorrhea after a year of using it. So, altogether I think this is a great option. I use it in my patients who are perimenopausal to bridge them into menopause when they don't need any treatment anymore for fibroid because of our discussion earlier (i.e., lack of estrogen and progesterone). I also use it in my younger patients with fibroids who want to preserve their future fertility because the other option is myomectomy. And we talked about the risks of surgery in general. But specifically for myomectomy, fibroids, unfortunately, tend to come back [17]. So instead of having multiple surgeries and so on, I think younger patients with fibroids are excellent candidates for relugolix combination therapy.

And even in the middle age group, I think medical treatment options are an excellent alternative to surgery also for that group. So, all in all, I am very excited that now in the fibroid field we have these nonsurgical FDA-approved oral treatment options.

And I agree with you, Sateria, that hopefully the patients will also know about these options so they can have an effective discussion and conversation with their health care providers.

Sateria Venable:

I couldn’t agree more, and the only thing that I would like to add is that medical therapies can be a phenomenal bridge from perimenopause into menopause. So, that's another great application.

Ayman Al-Hendy:

Sateria, this has been a pleasure to share this podcast with you and thanks for all the important information you shared and congratulations on all the amazing work you and the Fibroid Foundation are doing to support patients with uterine fibroids.

Sateria Venable:

Thank you, Dr. Al-Hendy. It's been such a pleasure to speak with you today. And we in the patient community appreciate all that you do to try to make our patient journeys better as well.