Alan Wein: Hello again. I'm Alan Wein from UroToday, and it's my great pleasure to have the opportunity to interview Melissa Kaufman, who chaired the AUA Guideline Committee on genitourinary syndrome of menopause. I think something that, it's a phrase that a lot of us repeat perhaps when we see patients, but I'm not sure that anyone has a clear understanding of what it means until after Melissa gives a talk about it.

Melissa Kaufman: Now, what about other urologic conditions? I mentioned this upfront, this is the genitourinary syndrome of menopause, right? Well, we want it to be very clear that patients with GSM and recurrent urinary tract infections, you should recommend low dose vaginal estrogen because it is extraordinarily effective. There is very high level evidence in reducing the risk of future urinary tract infections. This one statement is one of the most important statements of this entire guideline, and it's actually reflected in our recurrent urinary tract infection guidelines as well. It will save agony for these patients. It will save hundreds of thousands of clinic visits.

It will save billions of dollars, and it's highly likely to save tens of thousands of lives to prevent urinary tract infections, which are one of the most prevalent conditions that drive women to seek care in their primary care office, in the urology office, and in the walk-in clinics. This one intervention could literally change the way that we practice medicine in this country and generally improve health in perimenopausal and postmenopausal women.

But it's not just urinary tract infections, it's also things like overactive bladder. We know the urethra, we know the bladder is highly, highly sensitized to all types of estrogens. And so repleting those estrogens with low dose vaginal estrogen can really substantially improve overactive bladder symptoms, urgency, frequency, even urgency incontinence. And so it is recommended not just in the GSM guidelines, but also reflected in our overactive bladder guidelines.

But there's always something new on the block, right? What about the lasers? Here's my patient. She comes in, she has vaginal burning, chronic dysuria. She had a hysterectomy, she's had breast cancer. She finished taking a selective estrogen receptor modulator treatment. She didn't want to use vaginal estrogen, so we gave her trial of moisturizer. She came back with modest improvement, but then she comes back because she saw an advertisement on social media and she wants her vagina rejuvenated. Right? So we had to find the data to answer this question. It is so prevalent, and there are many, many, many options that are available.

And unfortunately, the data doesn't support the use of any type of laser radio frequency specifically for the treatment of GSM-related dryness, discomfort, irritation, dysuria, quality of life, satisfaction, dyspareunia. It just didn't support the data, but there are a number of patients that still request treatment that don't want to utilize hormonal therapies, that may have failed non-hormonal interventions. So we specifically placed a statement that said although you should counsel patients that the evidence doesn't support the use, you may certainly employ lasers in your practice if you have undergone shared decision-making with the patient regarding these limitations in the data.

Now, the data is very mixed. There are not large randomized trials that utilize proper controls or some other placebo that may be mimicking some of the effects. So we wanted to make sure that we gave liberal counsel to patients so they could make their own decisions, and you will also be able to reflect the things that you've seen in your own practice. So it doesn't mean that you can't offer this to patients, you just need to counsel them, that the evidence that we've gained in our guidelines doesn't support the use.

Now, I get this question four times a day, "Doctor, you want to put me on this estrogen? I'm already on estrogen. I'm taking systemic estrogen." So we specifically address this question, and it turns out, we should offer local low-dose vaginal estrogen or vaginal dehydroepiandrosterone, or DHEA, to patients who are on systemic therapy. The systemic therapy does not seem to complement the same way at a topical level that low-dose vaginal estrogen does. So I have many patients who are on both therapies. Again, that local low-dose vaginal estrogen takes a minuscule spike in any systemic levels, and that only lasts less than eight hours.

So, it is a very, very brief spike in systemic estrogen that is well below the levels that you see for systemic estrogens. And what about follow up? So we've diagnosed the patient, we've given her appropriate treatment. What do we need to do to follow this patient? Well, that's going to be a real individualized clinical scenario about how you want to manage those follow-ups, but you should counsel them because I often see this. Patients will begin a therapy, they get incredibly better, and so they think they're cured and they stop and they regress, their symptoms progress.

So they need to be counseled that long-term treatment and follow-up may be required to manage the signs and symptoms. Now, telehealth is very popular. Is it reasonable after a period of time for these patients to be monitored by telehealth? Absolutely. You don't need to necessarily do follow-up exams if the patient has had a great response and is asymptomatic at that point. But long-term treatments are often required.

So just in conclusion, this is a prevalent condition. You're going to diagnose it with the symptoms that the patient tells you about, like dryness and irritation, pain, urgency, recurrent urinary tract infections, plus the signs that you see on a GU physical exam is really comorbid with other conditions like OAB and recurrent urinary tract infections in our mainstay of treatments, low-dose vaginal estrogen. You can offer it to those on systemic estrogen. There's a great safety profile established for breast cancer, and just let patients know this is not, we're going to do this for three months and then you're going to be better and you can titrate off. Ongoing treatment is really often required.

So again, only those who seek shall find, and I'm very appreciative to everyone who's engaged with this. Thank you for seeking. This again is the QR code for the guidelines. And I am delighted to take questions and thank you so much to UroToday for allowing us to give you this information that I do believe is going to transform the way that we treat some of our female patients.

Alan Wein: Terrific summary, that was great. So in order to achieve improvement in most patients, you should advise the patient that the therapy has to go on for at least how long?

Melissa Kaufman: So, I generally tell patients to expect to utilize the therapy for any of the symptoms that they have for three to six months before they see manifest benefit. So in my practice, that's the follow-up interval when I start some of these therapies, is that I'll have them back at about a three-month time mark where they should start seeing some benefit. In general, it does take a period of time.

There's always a bit of a delay from, you give them this great plan, they leave the office. Sometimes it takes a while to get the prescription, then it may not be utilized right away. Then there could be other questions regarding some of the safety profile that they don't recall that you spoke about or that someone else in their family has brought up to them. And so there's oftentimes a period of delay. I really do believe they start seeing symptomatic improvements sooner, but I like to see them back about a three-month mark, because that gives a little bit of latitude for all those other dynamics to manifest.

Alan Wein: What should you be looking for if, let's say four months of therapy, along with vaginal estrogen applied properly, plus moisturizers, if that doesn't work? I mean, what should you be looking for or what should you do, what should you do then?

Melissa Kaufman: Yeah, I get much more concerned that some of those topical symptoms are secondary to other conditions like lichen sclerosis. And so, I will engage sometimes because I'm comfortable treating some of these conditions, I might pivot to use things like a steroid cream for a period of time to see if I can get some resolution. But for those who are not, I'm very liberal as well to send to my gynecology colleagues to ensure that there's nothing else, because the vaginal lasers actually are FDA approved for that indication, right?

So that's what they're actually approved to be utilized for. And we have a great camaraderie and collaborative effort, and I think that that's important for this patient population because again, if they're not getting the appropriate response, just like if they don't get an appropriate response for overactive bladder treatments, then I'm going to pivot to something else and something potentially more interventional.

Alan Wein: As far as the vaginal laser therapy is concerned, there's been a lot of reports about whether it's useful, non-useful, etc, also in stress urinary incontinence.

Melissa Kaufman: True.

Alan Wein: That's not really the topic of this, but what do you think about that, as somebody who has such a large clinical practice? I mean, you must see a lot of these women who have SUI plus GSM. I mean, do you think vaginal laser at all improves the stress urinary incontinence portion of their symptoms?

Melissa Kaufman: So off-label, certainly. I also think that low-dose vaginal estrogen improves their stress incontinence symptoms. So there was a Cochrane Review a number of years ago that indicated that systemic estrogen therapies did not improve and may even worsen some of the stress incontinence symptoms, but the topical estrogens were beneficial. And I've seen that also in my practice.

And I can't not believe that remodeling of tissues that is accomplished with vaginal laser in certain situations where there's not a substantial degree of hyper mobility may actually improve because you're improving the tissues in the urethra, you're improving the pelvic floor muscles, you're improving the coaptation of the channel, and just in general vaginal health. And I think those things absolutely will potentiate and improve to some degree the stress incontinence.

The other thing that lasers do that kind of harkens back to when you talked about some of the clinical trials that I'm involved in with stem cell therapies, is that it's a potential that another mechanism is not just the collagen remodeling, but actually invoking some type of injury to the tissue that will then provoke stem cells and paracrine effects and bring in other growth factors, and allow a real tissue remodeling and remodeling of that muscular tissue surrounding the external sphincter as well.

So yes, I think that there's potential, the way that we're utilizing them now in the way that we have the therapy focused now is not optimized for that. But I do believe that there's a great deal of potential for using those types of technologies for primary treatment of stress incontinence in the future.

Alan Wein: What's your favorite laser, if you're going to use one?

Melissa Kaufman: Well, I can't give you the brand name, but.

Alan Wein: No, no, no, I mean just the type. Carbon dioxide, Erbium? What type do you use when you're sort of either by choice or by patient pushed because they don't want anything else, when if you're pushed into that type of therapy?

Melissa Kaufman: Yeah. The most popular are the CO₂ lasers, and that's the one we have in our clinic.

Alan Wein: Gotcha. And when you follow these up, it's okay to follow them up just symptom-wise, as long as you tell them they need to continue the therapy? It's not necessary to do a vaginal exam to see whether you think the tissue is improved at all?

Melissa Kaufman: That's a great point. Just like it's not necessarily necessary to do a follow-up urine culture for a patient with a recurrent UTI that has symptomatic improvement with your treatments. We had no indication that it was important to do follow-up exams for a patient that has resolution of their symptoms with your treatments.

And I think although we've asked on the initial parts of the guideline, the initial statements, that we do need to do a genitourinary exam, the same holds true for overactive bladder. You should do a genitourinary exam for overactive bladder, but in every situation, is it critical to do that if it's not convenient for the patient, if you're providing trauma-informed care? If you're doing a telehealth visit to start with, do you want to withhold treatment that in general is not going to cause any significant risk to the patient?

I think that it's reasonable if you're going to do a telehealth first, you do need to do an exam at some point, but that you can go ahead and counsel and initiate therapies upfront, because this is such a prevalent condition and we have an absolute enormous number of patients that I think need to be reached. And so, make it as easy as possible on you and the patient to begin to get them treatments.

Alan Wein: Well, that was a great summary. I think that you've answered all the questions that I think most people who see patients like this would have. Is there anything else that we've left out that you want to bring up?

Melissa Kaufman: Just again, that this is so prevalent and I just have such a deep appreciation to everybody who is engaged. That this treatment, if given effectively and efficiently to the millions of women that are going to benefit from it, it will save lives. It will save enormous amounts of suffering in the population. And I believe in the end, it's really big enough to transform the way that we see women's health and will be the cornerstone, the absolute cornerstone of all the next series of innovations, just as we've already discussed, that are focused on women's conditions.

Alan Wein: Well, congratulations to you and your committee for doing this. I think the urologic public and also the gynecologic public are going to benefit from this. And I suspect that everybody will be snapping a picture of that QR code to go back and read the entire guideline. So, thank you so much, really appreciate it.

Melissa Kaufman: Thank you.