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, Dr. Wein had asked as well, what are the other things that you may be looking for? Well, anything that's outside the expectations of what you may see with loss of estrogen and androgens in these tissues. If you see something, that it's very pale, looks like lichen sclerosis, if you see masses, anything that's bleeding, anything worrisome, if you're not comfortable continuing to manage that, then please absolutely send to an expert, one of your gynecology colleagues who can then take over and potentially perform biopsies as needed or other treatments that may be indicated.

So you see this, the patient comes in, she's got all these symptoms. What is our best management option for the vast majority of patients? Well, it is fundamental to supplement estrogen into this tissue. So clinicians should offer the option of low dose vaginal estrogen in patients with GSM, in order to improve a lot of these symptoms, the vulva vaginal discomfort, the irritation, the dryness, the dyspareunia.

And we have lots and lots of different treatment options for vaginal estrogen. And we have Premarin and Estrace, all these things that have been around for literally decades. There are newer ones that are actually systemic estrogen receptor modulators. Depending on the patient's preference, they may choose to not have an actual cream that they find messy or inconvenient to insert, and they may choose to use a vaginal insert of a tablet for patients who are more compromised, who may not be sexually active, who need some help with these types of supplementations, utilizing an estradiol ring that only has to be replaced every three months may be indicated. And then we have new types of vaginal inserts that have DHEA, which actually metabolizes and gives both androgens and estrogens to the tissues. So, lots of different treatment options we have in the guidelines. A table with all the dosages and different types of options that are available for you to prescribe.

Alan Wein: Very good. Melissa, for the creams, do these or should these be applied to the entire vagina, or just-

Melissa Kaufman: That is an excellent question. So the way that I think the best practice is to have the patient, if they're comfortable using the applicator, that's fine. I find that most patients are more comfortable putting some on, a drop on top of their finger, one gram. They'll measure out one gram one time to know how much, put it on the finger. And then Dr. Wein, if I put face cream on and just dabbed it on my face in the morning, I don't think it would work very well. Right? You've got to actually rub this in to the vaginal tissue and you can use it, I want them to put it up in the vault as far as they can get. I want them to put it on the external tissues that are uncomfortable, everywhere that they can get it. And it will leach out so I ask them to do it at nighttime so it doesn't cause as much of a problem on their underwear. They may even need to use a small panty liner after they've inserted it, but it is remarkably, remarkably effective.

And another thing that comes up is that not only how to apply it, but the length of time to apply it. So for most of these creams, they are two to three times a week I'll ask them to do it, and it may take several months, three to six months to manifest full benefit. But you know, it's estrogen, and it's estrogen, we've all heard all about estrogen for a long time now. When that patient comes back to your clinic and they say, "Dr. Kaufman, I opened up that box and there's a big black box warning on it and my daughter doesn't want me to use it. Why are you trying to give me endometrial cancer, cardiovascular disease, breast cancer, and dementia?" Well, where did this actually come from? So, this black box warning emanated from the Women's Health Initiative, so way back in 2002, and it linked systemic estrogen, progesterone treatments to some of these conditions. So they put the black box warning in there in 2003, and by 2004, they backtracked and said, "Well, maybe estrogen only, there's no breast cancer risk." And then there've been numerous petitions to have this removed. And as a matter of fact, there was an FDA meeting last week to have this removed for low dose vaginal estrogen. So this was never intended for the type of topical estrogen treatments that have very, very little and only transient systemic absorption.

So, there is truly an absence of evidence that links low dose vaginal estrogens, the way that we have promoted prescribing them in this guideline, to the development of breast cancer. And patients should be informed of this. Because it is a major barrier to many women undergoing treatment.

So for cardiovascular disease, the same holds true. In these postmenopausal women, we can reassure regarding the safety of treatment. The risk of cardiovascular disease were not elevated.

Again, for breast cancer, the use of vaginal estrogen tablets was not elevated, even if you increase the duration and intensity. Not associated. So you can reassure your patients about the safety of treatment. And even women who have had breast cancer, reassurance. There was an even decrease in mortality, a decrease in mortality in patients on vaginal estrogen who had had breast cancer. Again, these are also shared decision making, not just with the patient, but certainly for a cancer patient with their medical oncologist. That being said, many will go ahead and already have prescribed some of these interventions knowing what the patients may be going through with regards to GSM.

And what about endometrial cancers? This seems like a very, very important subject. And indeed, when we looked at the literature, patients with GSM with low dose vaginal estrogen, it did not increase the risk for endometrial hyperplasia or endometrial cancers. So this is very important. So there is really no reason that a woman who is on low dose vaginal estrogen with an intact uterus should need surveillance biopsies or anything. Now, of course, any patient, any postmenopausal woman who has abnormal bleeding needs to undergo evaluation. But in general, for this patient population, so an intact uterus on low dose vaginal estrogen, you do not need to do any type of prior biopsy or endometrial surveillance.

But there are a lot of women who want some other type of non-hormonal intervention. So, what kind of data did we uncover and find about non-hormonal interventions in the guidelines? Well, we found that you should recommend use of vaginal moisturizers and lubricants, either alone or in combination with other therapies, generally to improve vaginal dryness and certainly the use of lubricants for dyspareunia. Now, I just want to take a moment to kind of differentiate these two. Moisturizers are really intended to mimic the natural secretions of an estrogenized vagina. And so they can be used every day, they can be used multiple times per day. Lubricants are designed to alleviate discomfort during sexual activity, so they're only used for cause. And in general, they can have water-based, silicone based, oil-based, and they will both be important for your patients with GSM. So you should recommend their use, but oftentimes, this is in combination with something like a low dose vaginal estrogen.

Alan Wein: So the moisturizers you use in conjunction with the estrogen therapy?

Melissa Kaufman: Absolutely, absolutely. So, I will have women who are using vaginal moisturizers, use them daily or use them on the days that they're not using estrogen, just to keep a moisture content within the vagina, so there's not any time where they might have some symptoms in between estrogen use.