373. Sexual Health: Cervix, Vulva, and Vulvodynia Research

Summary

Podcast Summary

You Are Not Broken – Episode 373: Sexual Health: Cervix, Vulva, and Vulvodynia Research

Host: Dr. Kelly Casperson, MD
Guest: Dr. Andrew Goldstein
Date: May 31, 2026

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Episode Overview

This forward-thinking episode dives deep into the often-overlooked topics of cervical and vulvar sexual function, the consequences of cervical procedures, the complexities of vulvodynia (chronic vulvar pain), and leading-edge research into treatments for vulvar pain and lichen sclerosus. Dr. Andrew Goldstein, a renowned gynecologic researcher, shares new scientific understandings, exciting clinical trials, practical pearls for patients and providers, and the importance of research participation in advancing women's sexual health.

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Key Discussion Points & Insights

1. The Cervix: Ignored but Important for Sexual Function

• Cervix's Role in Sexual Pleasure
  • The cervix is triply innervated, including by the vagus nerve. Even women with spinal cord injuries can experience cervical orgasm due to this unique innervation ([01:04]).
  • Dr. Goldstein stresses that interventions on the cervix, such as LEEP procedures for precancer, can cause nerve damage leading to sexual and urinary dysfunction—not common, but significant.
    • “If you just take off the very superficial top layer of the abnormal skin and you don’t go deep into the cervix, you don’t cause nerve injury. But a lot of people… go too deeply and… cause damage to the nerves.” – Dr. Goldstein ([02:32]).
• LEEP Procedures & Technique Matters
  • Goal: remove precancerous tissue without deep nerve damage.
  • Teaching around the world on proper LEEP method to minimize sexual dysfunction, infertility, and incontinence ([04:35]).
• Cervical Cancer Incidence
  • US: Rare due to screening and HPV vaccination; leading cause of death in resource-poor countries.
  • Vaccine's benefit extends to prevention of cervical, throat, anal, and rarely, penile cancers ([07:57]).

2. Vulva: Anatomy, Language, and Research Gaps

• Vulvar Anatomy & Terminology
  • The vulva comprises the labia majora and minora, clitoris, perineum, and more—distinct from the vagina.
  • Societal discomfort with the word "vulva" continues to hinder education and research ([09:00]).
    • “If you call everything the vagina, that’s like ignoring your face and calling everything your throat.” – (quoting Matthew Broussard) ([09:42]).
• Chronic Vulvar Pain (Vulvodynia)
  • Previously a ‘black box’; now known to have multiple causes, much like chest pain ([10:30]).
  • Dr. Goldstein initiated the first-ever Vulvodynia Therapeutics Research Summit (“shark tank but for the vulva”), leading to four high-priority research projects ([12:10]).

3. Breakthrough Research in Vulvodynia & Vulvar Disorders

a) Ketotifen Topical for Mast Cell-Mediated Vulvodynia

• Ketotifen: an antihistamine eyedrop being repurposed topically for vulvodynia ([13:26]).
• Mast cells implicated, especially in women with history of chronic infections or allergic reactions in the vulva ([15:02]).
• Not all vulvodynia—just mast cell-driven cases.
  • “Mast cells are really the OG bad boy of vulvodynia.” – Dr. Goldstein ([15:02])
• Condom test for semen allergy: “You can also take the semen and rub it on the arm, and if it turns red and gets itchy, that will also do it as well.” ([15:32])
• Study funded by National Vulvodynia Association & Gynecological Cancers Research Foundation ([16:23]).

b) Riciniferatoxin Injection (“Botanical Nerve Eraser”)

• Derived from Moroccan cactus; obliterates ONLY pain fibers in the vestibule.
• Potentially could replace surgical vestibulectomy; phase 1 trial soon ([20:06]).
  • “We believe that if you inject this chemical... those nerve endings are going to be completely obliterated. But all the rest...are left completely untouched.” ([19:00])
• Proof of concept from Morton's neuroma studies, showing long-lasting effects ([21:02]).

c) Botulinum Toxin (Botox and Xeomin) Injections for Pelvic Floor Muscle Vulvodynia

• Many women with vulvodynia have chronic pelvic floor muscle spasm ([22:36]).
• Standard PT sometimes inadequate; Botox and relatives can help muscles relearn to relax.
• New study uses 300 units (a high, appropriate dose) in repeated injections, gold standard, placebo-controlled ([27:00]).
  • “Physical therapy by itself is like trying to stretch a rubber band... muscles have been so tight for so long.” ([25:32])
• Aims for eventual FDA approval for insurance reimbursement ([29:03]).

d) Lichen Sclerosus: New Treatments in the Pipeline

• Risks and Realities
  • Chronic inflammatory skin disease; increases risk of vulvar cancer (~3-5%, most risk in untreated or severe cases) ([31:00]).
    • “The relative risk of developing vulvar cancer if you have lichen sclerosis...is double the relative risk of developing cancer than living down the street from Chernobyl.” – Dr. Goldstein ([33:23])
  • Topical steroids work, but side effects/thinning possible with overuse ([35:17]).
• JAK Inhibitor Topical Treatment
  • Dr. Goldstein’s research pinpointed the JAK-STAT pathway as a therapeutic target.
  • New phase 2 and phase 3 trials of topical JAK inhibitors (Opzelura, Delgocitinib) may provide alternatives to steroids ([36:12]).
• Silicone Barrier (Strata) for Resistant Symptoms
  • For the 25% still symptomatic despite steroids: new topical silicone-based product creates a protective film ([41:00]).
    • “It actually feels like silk. It goes on and it feels so nice. It actually helps the skin.” ([41:00])
  • Multi-center trial in NY, DC, Tampa, Salt Lake City.

4. How to Access/Participate in Research

• Centralized info: vulvodynia.com/research and clinicaltrials.gov ([42:39]).

5. Future Treatments: Topical Sildenafil for Arousal

• Topical sildenafil (Viagra cream) in development for female arousal disorder by DARE Bioscience, with a proprietary cream enabling actual absorption.
  • “If you go to your regular compounding pharmacy and they try to make a cream of that...it's all placebo because that medicine is not getting into the tissue. Darre Sildenafil cream does.” ([47:09])
• Available soon through a licensed compounding pharmacy ([43:34]).

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Notable Quotes & Memorable Moments

• On Cervical Nerve Damage:
  “This thermal damage may even be worse type of damage than a hysterectomy because the nerves die back all the way to the autonomic plexus.” – Dr. Goldstein ([06:01])
• On Societal Discomfort:
  “We can’t even say these words. And nobody knows what it means anyways. So podcasts are our last bastion of education.” – Dr. Casperson ([08:34])
• On Research Advocacy:
  “We’ve sort of brought the horse to the water, and women aren’t horses, but women need to drink. They have to participate.” – Dr. Goldstein ([48:58])
• On Accurate Vulvar Terminology:
  “If you call everything the vagina, that’s like ignoring your face and calling everything your throat.” ([09:42])
• On Innovation:
  “The plan is going to be [injecting riciniferatoxin]… knock on wood, they’re going to wake up, other pain nerve fibers are going to be gone, and their pain is going to be cured.” ([20:19])
• On Cancer Risk:
  “The relative risk...is double the relative risk of developing cancer than living down the street from Chernobyl.” ([33:23])
• On Placebo vs. Real Medication:
  “If that [sildenafil] works for you, it’s all placebo because that medicine is not getting into the tissue. Darre Sildenafil cream does.” ([47:09])
• Call to Action:
  “It’s also really important that when you do a study that these studies enroll quickly. If a study enrolls very slowly, pharmaceutical companies… will say women’s health issues are not important.” ([48:58])

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Timestamps for Important Segments

• Cervix, innervation, LEEP, and sexual function: [00:36] – [07:15]
• HPV vaccination & cancer prevention: [07:15] – [08:34]
• Vulvar anatomy, language, and societal issues: [08:34] – [10:21]
• Vulvodynia: causes, advocacy, and research summit: [10:30] – [13:26]
• 1st breakthrough: Ketotifen/mast cell therapy: [13:26] – [17:41]
• 2nd breakthrough: Riciniferatoxin injection: [18:03] – [22:31]
• 3rd breakthrough: Botox/Xeomin in muscle spasm: [22:36] – [30:26]
• Lichen sclerosus: steroids, JAK inhibitors, cancer risk: [30:29] – [41:09]
• Silicone barrier for lichen sclerosus: [41:09] – [42:28]
• Research study participation info: [42:28] – [43:20]
• Topical sildenafil for arousal, absorption details: [43:20] – [47:57]
• Research participation urgency and hope: [48:58] – [51:30]

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Resources & How To Get Involved

• Vulvodynia research: vulvodynia.com/research
• Clinical trial info: clinicaltrials.gov
• To support research/foundation: gyncancer.org
• Patient advocacy: National Vulvodynia Association, Tight Lipped

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Tone Notes

• Candid, evidence-driven, laced with humor and practical advice
• Both speakers are passionate about ensuring women's sexual pain is taken seriously and that hope is on the horizon

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For Listeners

This episode is essential listening for patients, providers, and anyone invested in women’s sexual health. It delivers not only up-to-the-minute clinical research, but also optimism and practical avenues for involvement in a new era of discovery around vulvar and cervical health.

Transcript

[A]

Welcome to youo Are Not Broken, the podcast that challenges everything we've been taught about midlife hormones and sexuality. I'm Dr. Kelly Casperson, board certified urologist, author and a leading voice in women's sexual and hormone health. Enjoy the show. Hey everybody. Welcome back to the youe Are Not Broken podcast. I'm here with my friend Dr. Andrew Goldstein, who is a time traveler and a world traveler and it's hard to nail him down. So thank you for finding the time to come back on the podcast.

[B]

I'm so excited being here.

[A]

We often talk about the vulva when you are on the show and today will be no different.

[B]

We like the vulva. We like the cervix too though, by the way.

[A]

Oh man, we never talk about the cervix. Let's start with the fact that another Goldstein, Dr. Erwin Goldstein, published some data on cervical innervation with sexual pleasure. This is years ago. And then like I posted that in a physician Facebook group and a lot of OB GYNs were like, that's not true. They're small studies. Like people are dismissing sexual functions when it comes to the cervix. Where do you want to start with that?

[B]

That's very important actually. And one of the main reasons why it's so important is because we do interventions to the cervix that can cause disruption of the nerves to the cervix and therefore cause significant sexual dysfunction. Not in the majority of people, but it can happen. And so the cervix is really interesting because it has triply innervated. So that means there are three different nerves that go to the cerv. A nerve that most people have no idea called the vagus nerve. The vagus nerve doesn't even go down through the spine. It goes down through the abdominal cavity and it goes all the way down to the cervix. And that's why interestingly, people who have spinal cord transection, so you know, they cut spinal cords, they can even still have orgasm through the vagus innervation of the spinal of the cervix. But the reason we talk about that is, as you know, I spend a lot of my free time doing cervical cancer work in resource poor countries. One of the main interventions when people have advanced cervical pre cancer is we do a procedure called a leep, which is called a loop excision procedure. And basically what happens is that their skin or the epithelium of the cervix has precancerous changes. And you take this wire that has electricity and you cut out the bad stuff, you cut out the precancerous cells and you prevent women from developing cancer and dying of cervical cancer. Now, in the United States, not that many people die of cervical cancer. About 5,000 women a year die of cervical cancer. It's quite rare to die of cervical cancer in the United States because there's lots of screening for precancerous changes, Pap smears, and now HPV testing. But in resource poor countries, it's the leading cause of death or second leading cause of death in cancer causes death in women because they don't have the access to screening. And so especially also women living with hiv. It's a very, very common cause of death because women with HIV now are getting actually pretty good antiretroviral care, but they still are at great risk at cervical cancer. So one of the things I do, I have a foundation called the Gynecologic Cancers Research foundation. And we go to resource poor countries to do cervical cancer. And we go this year, we're going, this summer, we're going to Rwanda and we're gonna go to India, and we're gonna go to Uganda to do this. But one of the things we do is we do these leaps. Now it's incredibly important how to do the leaps, because the electricity that you use to remove the abnormal tissue causes thermal damage to, which means damage to the nerves. And so if you just take off the very superficial top layer of the abnormal skin and you don't go deep into the cervix, you don't cause nerve injury. But a lot of people do when they do these leaps, they actually unfortunately do go too deeply and they cause damage to the nerves that go to the cervix. And that causes sexual dysfunction. It also can cause dysfunction, urinary dysfunction, because these same autonomic nerves that go to the cervix also go to the urinary bladder. They also cause arousal problems because these are the nerves that are increased with blood flow. So I actually do a lot of time when I do go to these countries, I do a lot of LEEP workshops. In fact, I was just in India two weeks ago doing a leap workshop and I was teaching the physicians how to just go just right across the top of the cervix instead of taking a big cone down the cervix, because that cone is what causes the problem. I like talking about the cervix because I think it's very important to prevent cervical cancer death in resource poor countries. But how you do this, you don't Want to cause other problems. Now, if you take a big old scoop out as well, you can increase the risk of cervical incompetence or preterm labor. So it's not just what procedure you do, it's really how you do it. And so we do a lot of teaching how to treat the pre cancer, but also not cause sexual dysfunction and preterm delivery.

[A]

And I think for the people listening, whether they're on the provider side of things or dear the patient of, like, if your sexual function is derived at least in part from deep penetration, cervical arousal, it's valid, it's real. If you're headed into a hysterectomy, it's a conversation to have with people of, is this cervical sparing, is it not cervical sparing, like the cervix is part of sexual function? Not for everybody, but for many people.

[B]

Right. And I think this, the problem is this, this thermal damage may even be worse type of damage than a hysterectomy because the nerves die back all the way to the autonomic plexus. So it actually may be worse for sexual function than even if you left the cervix to remove the cervix and hysterectomy. So, so it's just important, and I know this is sort of esoteric and maybe a little esoteric for, but important thing is that if someone's doing a leap, there are lots of different shapes of these loops that you can use. And I will tell you, 90% of them are too big. You really only want the ones that are broad and shallow. And if there's precancerous changes that are going down the canal of the cervix, what you want to do is still take a broad, shallow scoop of the tissue right across just the superficial surface, and then do something called a top hat, where you just go right down the cervical canal, but you don't really go into the stroma or the muscle part, part of the, of the, of the cervix and thereby not causing this thermal damage to the nerves. So it is important. Obviously, we're saving these women's lives, but at the same time, we don't want to save their lives and cause other problems.

[A]

Yeah, absolutely. Can you confirm that? To my knowledge, Ireland and Australia have eliminated cervical cancer now because of their vaccine programs.

[B]

They're certainly on that way greatly reduced. Even in the US we're seeing a reduction because even though only about 40% of we are making a. Even though 40% of people are getting full vaccines, were Some herd immunity in that. Now, the difference in the US Is the majority of people who get cervical cancer in the US Are immigrants. And so we're not gonna see the same decreases you would in countries that have less immigration.

[A]

You can get the vaccine up to age 45, now 46, I think so.

[B]

I think that's what it's approved for. Again, we are also lucky in that our vaccines here cover more strains than most of the vaccines around the world. So we're lucky, but we need both young girls and young boys, 9 to 12, to get the vaccine, because, of course, it's not the HPV virus that causes cervical cancer. So it doesn't just cause cervical cancer. It causes throat and mouth cancers as well, and anal cancer. It's really important. And penile cancer? Rarely, but rarely. But it does cause penile cancer.

[A]

Right, Fascinating. Okay, let's move on to the vulva. What's the vulva? It's a word we can't say on the Internet, I will have you know. So we really need to keep talking about it. A massive account of, like, 700 or 800,000 just got kicked off of Instagram for educating about the clitoris. So everybody's very, very much like, oh, my Lord, we can't even say these words. And nobody knows what it means anyways. So podcasts are our last bastion of education. Dr. Goldstein.

[B]

Okay, so let's talk. So the vulva, the external genitalia, and that includes the labia majora, the. The large labia, the area between the large and small labia. So that's called the intralabial sulcus. Then the small labia, which are the labia minora. And the size of the labia minor are greatly variable. Some people have large labia minor, some have very diminutive ones, but it doesn't matter for sexual function. And then the clitoris, the hood of the clitoris, and the perineum, that's the whole vulva. One of my favorite chameleons said, if you call everything the vagina, that's like ignoring your face and calling everything your throat. So it's.

[A]

Who said that? That's really good.

[B]

I know it's good. I can't. I think Matthew Broussard, I think, is his name. He's a really. He's a really. He's a really funny guy. His mother taught him to use anatomic terms. And he says when he was fooling around with his girlfriend and he started using the term vulva, his girlfriend said, stop saying that. And he would go, vulva. Vulva. Vulva. So I don't mean to be stealing his bit, but he's very funny regardless. The vulva, the external genitalia, they're very important, but they get very little attention paid to them in the medical literature compared to the uterus, the ovaries, the

[A]

vagina, or the male external genitalia. Men have external genitalia and internal genitalia, too. I mean, prostate.

[B]

That's true, that's true. So it is unfortunate that it doesn't get as much information, but I think one of the great things, the reason I'm asked to come back on really was because one of the problems with the vulva is a pain condition called vulvodynia. The definition just means three months of chronic vulvar pain of an unknown cause. Now, when I started practicing medicine, as you can tell from all this gray hair, that was a while back. And vulvodynia was this black box where we don't know what's going on, we don't know what causes it, we don't know how to treat it, and women never get better. But that was about 25 years ago. But in the last 20, even 15 years, we've really been able to crack open that black box and figure out the causes of vulvan. And we realized that just like if someone has chest pain, there are many causes of chest pain, whether that's a heart attack or a panic attack or a broken rib. There are multiple causes of vulvar pain. And we've really done some amazing research in the last, again, 15 plus years to figure out the causes of vulvodynia. But unfortunately, the treatments have really not. We didn't make as much progress. But I'm on here, this podcast, this great podcast to tell you that we really are trying to make progress now. Two years ago, I was very frustrated. I said, we've been doing this for 25 years now, and again, we've learned a lot, but we haven't moved the needle very much in treatment.

[A]

Thank you for having your existential crisis about vulvodynia. What am I even here for if we haven't done anything?

[B]

So what I did was, and really sort of was I went to several societies. One was the International Soc for the Study of Women's Sexual Health, and two really amazing patient advocacy groups. One is called the National Vulvodynia association, the NVA National Vulvodynia association, and one called Tight Lipped. And we're great patient advocacy groups. And I went to them. I said, what we really need is a vulvodynia therapeutics research summit. I envisioned this sort of like shark tank, but for the vulva, which was a panel of really 15 of the world's best vulvodynia experts. And the plan was everyone had to come with an idea, a new idea, a new treatment, not that everyone was trying. And we had to pitch it. It was like an elevator pitch, except it was longer because we all had about a half an hour and we got to bring slides, and everyone came with their new idea. And then at the end, we would debate them and we would throw critical acid on these ideas. And then we all voted on. It was really great. It was really great. But because there was such passion, I'm

[A]

glad you voted anonymously. So just the loudest person didn't win.

[B]

Yeah, so we all voted anonymously afterwards. And then we took, you know, and then we actually published the results of this. Of this survey. So it's very clear as to how we did this because we did this with scientific rigor. And I'm here to tell you, really, the top several of these choices now are being studied. And that's really what I wanted to get on to say. So the first, the thing that was voted number one, and it was not my idea, by the way, mine was number five, and I'm really so mad about it. But okay, the one that was ranked number one was something called ketotifen. Now, ketotifen is a chemical that is actually approved as eye drops for inflammation of eye drops with severe allergic blepharitis and severe allergies of the eye. But. But one of the causes of vulvodynia that we've learned is that a specific type of white blood cell called mast cells are very instrumental in vulvodynia. Mast cells secrete lots of inflammatory chemicals. Histamine is one that you may all be familiar with because it's the same thing that mosquitoes inject in you, and it causes that swelling, redness, and itching. But mast cells secrete something called nerve growth factor, which causes too many nerves to grow, so that's of vulvodynia. And mast cells can overreact to yeast infections and they can overreact to allergic reactions. And so mast cells are really the. The OG bad boy of vulvodynia.

[A]

I want to go way off on a tangent so I don't lose it when women say, I feel like I'm allergic to sperm or semen, meaning when we have sex with a condom it's not a problem. When we have sex without a condom, I get this horrible reaction afterwards. You think that's mast cell?

[B]

Of course it's mast cell. But I mean, it's an allergic. It's an allergic reaction. It's an allergic reaction. Now, it's very uncommon. It's very uncommon. But it does. But it's rare.

[A]

But the condom test is, like, a pretty brilliant way to figure that out, right? Because it's not pelvic floor pain because it's just sex. Or X, Y, and Z. It's like, no.

[B]

You can also take the semen and rub it in the arm, and if it turns red and gets itchy, that will also do it as well. Because you can't have just an allergic reaction in the vagina. If you have an allergy, you have an allergy throughout your whole body because it's an immune response.

[A]

Can you have an allergy to some person's semen but not another person's seme?

[B]

It is theoretically possible, although it seems like that when you've been sensitized, you typically are reactive to semen.

[A]

Okay, thank you.

[B]

But again, that's the way I was saying. That's pretty uncommon. I was actually, before there were podcasts, there were television shows, and there was a television show on the Discovery Channel called Strange Sex. And actually, I think about 15, 18 years ago, I was on Strange Sex about semen allergy. So I hadn't thought about it for about 10 or 15 years, but again, great. Okay. So the first study. That's ketotifen.

[A]

Ketotifen.

[B]

Ketotifen, yep. And it's a topical. And the study is being sponsored by the National Vulvodynia association and my private foundation, which is called the Gynecologic Cancers Research Foundation. We do other things. Again, I do a lot of cervical cancer stuff, but we also fund other gynecologic problems. So if you care about even funding vulvodynia research, you can go to gyncancer.org gyncancer.org and if you want to contribute to vulvodynia research as well. So the first study is topical ketotifen for vulvodynia. So a very specific type of vulvodynia called an inflammatory vestibulodynia, that means pain at the entrance, just at the entrance of the vagina, called the vestibule, due to inflammation and too many nerve endings called neuroproliferation. So we're very excited because that was ranked number one, a choice of all the experts. And by the way, it wasn't just experts. We also had patient advocacy members there. So there were members from the National Vulvillini association and Tightlep, and they got to vote as well. So it wasn't just scientists. Patients and patient advocacy groups had an important say in the voting process as well.

[A]

And I think thank you for saying what it's specifically for, because I think vulvodynia is a grab bag. Vulvodynia literally means. Means pain in the vulva. Right. And it doesn't mean why. And the last thing I want is somebody with like, GSM or lichen sclerosis thinking like, hey, I heard about ketofen on this podcast of like, it's a specific type of vulvodynia that, that treatment's for any.

[B]

The type of vulvodynia that's, that's mediated by mast cells and people who develop it because of chronic infection, chronic yeast infections, allergic reactions, often to topical yeast medications, because they think they're. They think they have a yeast infection when they don't, or they're just using so much of it that they just get severe allergic reactions to it, or they get allergic reactions to the propylene glycol, which is the preservative in the yeast creams. So that's number one. The second study that has come out of this conference is a study that is not yet started, but is going to be sponsored by the National Institutes of Health. And that is a medicine called riciniferatoxin. The riciniferatoxin is actually from a cactus that's found in Morocco. And this is a very, very potent chemical that binds to nerve endings, and it binds to the nerve endings that are very specific that are causing pain and vulvodynia. So it only binds to nerve endings that cause pain. Cferent nociceptors, specifically type of nerve ending that only has the sensations of burning, rawness, and cutting. And so this chemical is so strong that it completely, if you put it. The plan is, if you. And we don't know because it's a phase one clinical trial, but we believe that if you inject this chemical into the vestibule, just the skin of the entrance, where women have too many nerve endings, that those nerve endings are going to be completely obliterated. But all the rest of the tissue, all the other nerve endings that are responsible for pleasure and pressure and arousal, and all of those other nerve endings are left completely untouched. The rest of the skin is left completely untouched, but only These pain nerve endings are completely destroyed. And this medicine is so strong that we expect it to happen in 15 minutes.

[A]

So we're not just numbing her pain, we're specifically knocking up the pain fibers but keeping all the other sensations. Is this going to replace surgical vestibulectomy? Yes.

[B]

That's cool. Which, as you know, that I've done like the most vestibulectomies of anyone in the country, the second most in the world. And I've always tried to make myself obsolete. And the goal is that I never have to do another one of these surgeries again. And so the plan is going to be that we're going to study this in 20 women. They'll go to sleep and we will inject this medicine into the. Just very superficially into the tissue, and we're going to wake them up 30 minutes later and knock on wood, they're going to wake up. Other pain nerve fibers are going to be gone and their pain is going to be cured.

[A]

Amazing. Is this long acting and permanent or do you think or do the pain nerve receptors grow back?

[B]

So it's a great question. So what we know is this is for this one condition has never been studied in human beings, but the same chemical is being studied by NIH and another condition called Morton's neuroma. Now, Morton's neuroma is when a person gets a ball of nerve endings in the foot and it's incredibly painful because it's the same type of nerve endings. And so it's almost like stepping on a nail every single time you step with these. Morton's neuroma. And they've done it on patients with Morton's neuroma. All the patients they've done have been 100% successful and were, I think, 8, 10, 12 months later, and none of them have grown back.

[A]

You've got proof of concept.

[B]

Proof of concept. We're very excited about this. I've been talking to the NIH about this study. Possible doing the study for 10 years, fits and starts and everything, but still has still more. More bureaucracy has to go through the NIH panels and the investigational review boards and things like that. But we're hoping that by the end of this year that we're going to start doing this in up to 20 women. And again, the goal would be to make myself obsolete to no more vestibulectomies and completely get rid of.

[A]

That's such a good way to end a career.

[B]

It would be. I would sleep well, I would sleep. It would be very great.

[A]

And be like, and we don't need this anymore. Good night, good night, and goodbye.

[B]

Exactly. So that's number two. We've got even more, which is, I mean, it's crazy how many good studies are going on. So now, one of the most common causes of vulvodynia are tight pelvic floor muscles. Now, tight pelvic floor muscles can be caused by many reasons, sometimes behaviorally. So people holding urine for a long period of time, those muscles can go into spasm. Sometimes women, because of anxiety or stress, sort of hold their stress into their. In their, in their pelvic floor muscles. You can have. Have low back pain, and that can cause you to have tight pelvic floor muscles, or you can have hip problems that can cause you to have tight pelvic floor muscles. You can be hypermobile, and that often causes you to tight pelvic floor muscles. Regardless, about 60% of women with vulvodynia, the main cause of their vulvodynia are tight pelvic floor muscles. For years, we've known that pelvic floor physical therapy can help women with this. But the problem with pelvic floor physical therapy is when women have been tight for a long period of time, the muscles are both tight and short. And the reason this causes pain is because this causes a constriction of the arterioles, or the small blood vessels. And that cuts down oxygen going to the muscles as well as the skin on top of the muscles. And when there's not enough oxygen going to both the muscles and the skin, the tissue has to live anaerobically, that means without oxygen. And the byproduct of anaerobic respiration is lactic acid. So lactic acid builds up in the muscle and in the skin. Now, lactic acid in the muscles causes the sensations of throbbing, aching, and soreness. But lactic acid in the skin causes burning and rawness. And so you get superficial skin tenderness right at the entrance, the back part of the entrance, and then you get deeper pain in the vagina from the tight muscles. And so this is a very, very, very common cause of vulvodynia. Now, physical therapy, what they're trying to do is sort of to stretch out the muscles to their normal length. But the problem with physical therapy by itself is it's like trying to stretch a rubber band because the muscles have been so tight for so long that they get stretched. But by the time the person's back in pt, next week, they're back again. So it's like two steps forward, one and three quarter steps back. So for many years, we've been using muscle relaxants to help physical therapists. One of the common muscle relaxants we've used are Valium suppositories. Valium is a very good muscle relaxant and that helps about 50% of the women, but not all the women. So a muscle relaxant that works much stronger is botulinum toxin. So the brand name of botulinum toxin, there's several. The one that most most commonly people know as Botox. But that's just one brand. There are other brands. There's Xeomin, there's Dysport, there's Jeuveau. And these are all different types of botulinum toxin. But what they do is they paralyze the muscle in a relaxed state so that the physical therapist can then stretch out the muscles to their normal length. Now, even though we've known this for a long time, and I've been treating women with botulinum toxin injections for probably 22, 23 years, since 20, since actually 2004. So 22 years, we've never had a really good study that used an adequate amount of botulinum toxin. And so the third study that I'm excited to tell you about is that finally we got one of These manufacturers called MERs, who makes the brand name Zeomin botulinum toxin. And we are doing a study of an adequate amount of this toxin. Because before people have done studies, but it's been. And just a little whiff, not enough or sort of like they would use the amount that you would use for if you inject the forehead. But these muscles are much too much thinner than the muscles of the pelvic floor. So they would use 20 units or 30 units.

[A]

Yeah. And I would think that the pelvic floor, that's a chronically contracted muscle, which might require more than say just a face, which isn't like pathologically chronically contracted.

[B]

Yep. So what's, what's exciting is that the study is going to be a total of 300 units of botulinum toxin, 2 times 150 injected twice, separated by six weeks.

[A]

Is Xeomin units equivalent to Botox units?

[B]

That is correct. But essentially. So 100 Botox units for Xeomin units or Duveau units or all their equivalent. And so we have. And the other really great thing about it is that it is a well designed study and that is placebo controlled. So it's gonna match, you know, everyone. So it's gonna do the gold Standard study study. But everybody who got placebo initially will get the xeomin in an open label phase. So Basically people for 14 weeks they get their injections. If at the end of 14 weeks they were in the placebo, they will get the xeomin and they'll still get supervision and care by the investigating physician. So 100% of people who participate are going to get the medicine and it's about $5,000 worth of medicine for. So that study is only going to be done in my centers in New York city and Washington D.C. so if a woman unfortunately that's going to not be nationwide. But again, another really good study to get to new effective treatments for vulvodynia because as I said earlier, we've learned a lot about it, but we haven't moved the needle as much as necessary on treatments. So these are three very novel treatments getting to the heart of different causes of vulvodynia. And we're just super excited about it because we really can not only have we cracked open the box as to what the causes are, but I think we hopefully take it. We'll take a sledgehammer with now treatments.

[A]

Awesome. Is the goal of that of the Xeoman company with this test to then hopefully get FDA approval indication for it?

[B]

So yes, and I believe another one of the companies that makes one of these toxins is also very interested as well.

[A]

That means there's enough people suffering that it's worth it because these toxins are expensive and for people to have to pay cash and they do need to be repeated because they wear off. And so to get an FDA approval which can then get insurance coverage will be a game changer.

[B]

So that's why this is studied. This is designed even though it is not a true phase two trial because it's not going through the fda, it's designed exactly like a phase two trial with endpoints that have already been designed and approved, have been designed for FDA approval. And so basically this is proof of concept so that a drug company could go straight to phase three clinical trials. So again, really we're trying the. All three of these studies are gold standard studies. They're being designed so that they're all placebo controlled appropriately. They're really using the right endpoints. And again, I sound a little bit like a wonky scientist here, but the devil is in the details. But the details are very good. So I guess that's. I'm very pleased about all of these things.

[A]

That's wonderful. Do you want to get through your other Two.

[B]

Yeah. I'll tell you two more if we can. Now, there are other problems of the vulva other than vulvodynia. Other things that cause chronic vulva pain are skin diseases. And the most common skin disease that affects the vulva, which affects about 2% of women, is something called lichen sclerosis.

[A]

Just to be pedantic, I would say GSM is the most common skin disease of the vulva. We.

[B]

I don't know if you disease is an interesting. I would maybe call it a disease.

[A]

Symptomatic skin condition.

[B]

Yeah, I would call that right. And certainly should be treated. Obviously GSM should be treated, but lichen sclerosis is an autoimmune skin disease where the body, for whatever reason has decided that one part of the skin is not part of that woman and their immune system attacks the skin and it causes scarring of the vulva, it can cause severe itching of the vulva, and it can even cause vulvar cancer if not treated. 3 to 5% of women with lichen sclerosis will develop vulvar cancer.

[A]

I want to pick on that for a hot second because I think there's a big difference between severe, like severe lichen sclerosis. Mute this for anybody listening with children if you've made it this far. Severe lichen sclerosis is an absolute bitch. Like, it's brutal, but then there's like very mild. I'm just a little itchy. It's a teeny little thing. And we don't have a scale for severity of lichen cirrhosis that I'm aware of. But here's my question. The risk of vulvar cancer, do we need to be scaring Every. All the 2% with lichen sclerosis, or are we talking like, the severe ones are much more likely to progress than that? Like one little spot that's itchy sometimes. But we're calling it like the sclerosis.

[B]

I don't think we know that, but we certainly know the longer standing disease is more likely. So the thicker the lesions, even if it's small, a thicker lesion is more likely to become dysplastic and cancerous. And it's the chronic inflammation allows methylation of the genes, which allow the oncogenes to turn into dysplasia and cancer.

[A]

Perfect. Because I think we can go both ways. We can be like, hey, everybody needs to know there is a risk of vulvar cancer with lichen sclerosis. But we don't need to freak everybody out about their Vulva all the time, that everybody with lichen sclerosis, sometimes we like over scare on this condition. I think I want to appropriately educate and not overly scare.

[B]

We don't want to scare. But also, even if they're not going to turn into cancer, chronic inflammation if not treated can cause continued scarring, and we certainly don't want that. And scarring can cause pain and sexual dysfunction.

[A]

The majority of vulvar cancer is not because of lichen sclerosis.

[B]

No, 60%. 60% of vulvar cancer is caused by lichen sclerosis, only 40% by HPV.

[A]

Okay, that's important, right?

[B]

And here's the other thing, and here's the other thing about it. Now again, it's still, it's still only 3 to 5% if not treated. If it's well treated, then the risk goes way, way, way down. So we want women to be well treated, treated. But I will tell you that the relative risk of developing vulvar cancer if you have lichen sclerosis, as opposed to not having lichen sclerosis, the relative risk is 250, which means that you're 25,000% more likely to develop vulvar cancer if you have lichen sclerosis than if you don't have lichen sclerosis. And let me put that in perspective. If you live down the street when Chernobyl exploded in the Ukraine, remember Chernobyl? I know for your age and all of this radiation went in the air, your relative risk of Getting Cancer was 131. This is 250. So this is double the relative risk of developing cancer than living down the street from Chernobyl. Now I know there's that saying. Lies, damn lies and statistics. And again, you have to sort of understand this stuff. But let's not underplay the risk of cancer. We, what we need to do is tell women they need to be appropriately treated.

[A]

Perfect, that's helpful. I'm glad, I'm glad we went on that tangent. That was useful.

[B]

Okay. But then here's the exciting thing about appropriate treatment. So we've known since the mid to late 90s that topical steroids, corticosteroids, treat lichen sclerosis. But they have to be very strong corticosteroids. They have to be what is known as clobatazole, which is an ultra potent

[A]

corticosteroid cream or ointment or does it matter? Just get whatever's cheaper.

[B]

Ointment. No, ointment, ointment. Because it gets, when it gets absorbed into the skin and then it goes through the skin and then to the underlying fat layer. It's still active for 72 hours, whereas creams don't do that. So ointments are much better. And we've been using clobetazole for 25 plus years and we've lowered the risk of cancer and we've made women's lives much better who have lichen sclerosis with corticosteroids. But the big but is that the people do have side effects from corticosteroids. I don't want to overplay those risks, but people do have side effects, some of it. People, if you use too much of it, you can have thinning of the skin. If you use way too much of it, it gets absorbe in the body, which increases the risk of diabetes and cataracts and osteoporosis.

[A]

But I think most people underuse it.

[B]

I agree most people underuse it. But we would like a better mousetrap if possible. So four years ago now I did a study where I biopsied normal skin and then the sclerotic skin of the same woman. So people who had, you had biopsy the abnormal skin and then the adjacent normal skin. And we sent this, both of these skin biopsies to look at something called micro rna. And that basically tells you what genes are turned on and turned off in between the normal skin and the abnormal skin, the sclerotic skin. And we did this on 15 people and we were able to do through this study to figure out the exact inflammatory pathway that's active in lichen's chloride. And so before we knew it was chronic inflammation, but we didn't know exactly. And there are many inflammatory pathways. Now steroids work because they work like carpet bomb approach. They actually decrease inflammation on all of those pathways, but they also prevent other, they're not just anti inflammatory, they cause other, the side effects because they affect other important things like it prevents the formation of collagen, which is the skin is constantly remodeling it, but it prevents that. That's why the skin can thin with too much steroid use. But we were able to figure out the very specific inflammatory pathway that's active in lichen sclerosis and that's called the JAK STAT pathway. J A K S T A T and as soon as we published this study in cells three and a half years ago, my phone, well, didn't ring off the hook, but I got calls from multiple, multiple drug pharma companies that said wait a second here, Andrew we have topical JAK inhibitors that we're studying for a variety of things. Do you think it would work in lichen sclerosis? And I said, well, it certainly should. So we finished one, what is known as a phase 2 clinical trial of a JAK inhibitor, topical JAK inhibitor called Ruxlet Opzelura. And we actually just had that paper last week accepted for the Journal of the Academy of Dermatology, the big derm journal in the world. And that was just accepted for publication. So that's coming out really soon. Another company, another company that makes Delgocitinib, another topical JAK inhibitor, is now starting a Phase 3 clinical trial for FDA approved approval for a topical JAK inhibitor for lichen sclerosis. That is happening. There are going to be 60 sites across America, Canada and Europe who are doing the study. It's going to be 660 women. So it's a big study. So pharma is finally really taking an interest in women's health. And this is the first time that they're, you know, they're, they're doing a phase three trial for lake and sclerosis sclerosis and very exciting. I'm going to be the first site that's starting next year. We're actually getting initiated next week. So again, it's a topical JAK inhibitor for lichen sclerosis and that's going to be across America, Canada and Europe. And so that's super exciting. You don't have to just come to my site. So that's huge. So again, pharma companies are now interested in a little bit of women's health, which is a big change. And now we're doing one more lichenspros study. And then the last lichen sclerosis study we're doing is we're studying a topical silicone product that acts as a barrier on the skin for people who have lichen sclerosis who are well treated with steroids but who are still symptomatic. About 25% of women who are optimally treated with steroids still have symptoms. They still have irritation, they still have itching, they still have burning. And you don't want to use more steroids because then actually going to cause worse thinning of the skin and more irritative symptoms. So we have a new product called Strata that we're studying. It's an amazing product because it's used in burn victims and in chronic wound healing. And it puts this nice barrier that actually prevents bacteria from getting to the skin. And lichen sclerosis and that actually causes less, what we call oxidative stress and so therefore less inflammation in the skin of women with lichen sclerosis. So this is another very well done. So this is called Strata.

[A]

Is it sticky? What do you do with the hair?

[B]

It's crazy. It actually feels like silk. It goes on and it feels so nice. It actually helps the skin.

[A]

Is it like a silicone lube?

[B]

You know, it's proprietary, so I don't. It's like a film, but it's a very, very, very thin film. It doesn't. It's not like you feel crinkly or. And actually it's. It's just this. Imagine, I guess, like WD40. It actually adds this lubricant effect, but it's not sticky. And this is a very good trial because again, 25% of people who are even adequately or appropriately treated with steroids and are really optimally treated, but are still symptomatic, they need help. And so that's the study. Now, that study is only happening in our, actually four centers around the United States. States. It's happening in my center in New York and in Washington, D.C. it's happening in Dr. Jill Kraft, center for Vulvovaginal Disorders in Tampa, Florida, and it's happening in the University of Utah. Dr. Margaret Cox is doing it there. So four centers are doing that Strata study. We're almost finished recruiting. So if you're interested in doing the study, if you are. And it's only about four visits, so it's really not onerous. Even if you don't live exactly in one of these areas, it's only four visits over about four months. So there's some traveling, but it's not that onerous and we're very excited about that.

[A]

What's a good central repository for people listening to the podcast who are like, I know somebody, I have a patient, or maybe it's me, and I want to get more info on one of these studies. What's a good place for them to go?

[B]

So if you go to my website called vulvodynia.com and go under research, they will list all of our studies. So vulvodynia.com research and so all of these studies, when they're active, will get on that. So the riciniferatoxin, which is the one at nih, that's not there yet, and the other ones are, you know, they're all coming, but when they're active, they're going to be on that website. You can also go to clinicaltrials.gov which is the US's clinical trials registry. And all of our studies, and all these studies will be on ClinicalTrials.gov as well.

[A]

I love it. Thank you so much. Can I ask real quick, because I know you have expert knowledge on this. Before we wrap, topical sildenafil for the vulva for arousal. What's coming in the pipeline and what do we have available right now?

[B]

So there's a great small pharma company from California called Darre studying this atopical sildenafil, which is, which is Viagra for arousal disorder. So female sexual arousal disorder is women who have decreased in blood flow to the glans close clitoris, very similar to decreased blood flow in men who get erectile dysfunction. So when you have small vessel disease, when the arteries start to get a little clogged as you get older and cholesterol builds up, then one of the earlier symptoms of coronary or of any atherosclerosis is actually, I'm sure you've talked about this on your podcast, which is erectile dysfunction. But the equivalent in women is female sexual arousal disorder. Now, just like Viagra, which is sil, works really well for erectile dysfunction in men, SIL can work for women with arousal disorder. But Dari has been studying this medication as a cream instead of to get a lot of it just where you really want it to get the increase in blood flow to the vulva and to the clitoris. Now the question is, why don't you just take up, take a Viagra tablet and crush it up with a mortar and pestle and put it in Vaseline or some cream that you got and just rub it on your vulva. Why won't that work? Well, the reason is that sildenafil is a charged molecule. Charged molecules don't go through the skin. So that's, for example, why you have certain creams and others that you can't make into a cream cream. So you can have like asper cream, but you don't have ibuprofen cream because the ibuprofen won't get through the skin. And actually, now people, you may go to a compounding pharmacy and they may try to make it up for you and say, oh, here's the scream cream that has sildenafil in it. I'm going to tell you that it doesn't work. But what DARE has been studying for years now is they have a, they have a proprietary cream that has lots of salt in it. That essentially what that does is that cream pushes out the charged molecule from the cream through the skin. And so they actually have a cream that will get the sidonafil into the skin. So their Viagra cream, Sidanel cream will work. And the phase two studies showed that they did something called thermography where they could see the blood flow to the vulva. And after using this, the vulva lit up like, like a Christmas tree. And that was studied by Dr. Irwin Goldstein, no relation, but a very good friend. So that, so we know that now they have made that cream now available through one specific compounding pharmacy nationwide. And that's being rolled out. I don't even know exactly when it's being rolled out. I think it's available in some states are already it's going to be licensed eventually in all states. But can't confuse it with if you go to your regular compounding pharmacy and they try to make a cream of that or they may call it a scream cream or something like that. If that works for you, it's all placebo because that medicine is not getting into the tissue. Darre Sildenafil cream does.

[A]

That is the missing piece of information.

[B]

It really matters. And in fact this was a Harvard biomedical engineer who figured out out this cream. So this is a proprietary patented cream that actually. And by the way, they're looking at it for many different that cream for many other chemicals that normally you can't make into a cream form because anything that's a charged molecule will not get absorbed through the skin. But now if you have this cream that essentially forces the molecule out of the cream into the skin like with the sledgehammer. Well, like a chisel because it makes it go in that now there are lots of, lots of molecules that now make sense that they've never been able to make into a cream form.

[A]

This is a paid message from GoFundMe.

[B]

Meet Juan Naula.

[A]

When his son was hospitalized for a viral infection, Juan started a GoFundMe to pay for medical expenses.

[B]

It was 5k to pay the bill for my son and I need only 22 hours. It was amazing. People really trust on GoFundMe. How did Juan raise $5,000 in less than a day?

[A]

He posted a short video on GoFundMe telling his story in 30 seconds.

[B]

30 seconds. Be specific, be quick and tell what are you going to be using the funds for? I was nervous to do it because it doesn't feel okay to ask money. But you shouldn't be nervous. Sometimes you just have to do it and see the results. We were able to save my son's Life. Thanks to GoFundMe that we still have my son with us.

[A]

Start your GoFundMe today at gofundme.com that's gofundme.com gofundme.com this message reflects one person's experience. God bless scientists.

[B]

Well, science is important and real science. And so that's why it was so kind of you let me to come on. Because we've talked about real science for the last last hour, which is really using some basic science, really understanding the underlying causes of problems and then designing potential treatments, knowing what the underlying cause is. And that's it's relatively new and we're really certainly for women's health. And so we're finally just, we're designing good clinical trials to study. And I just would hope that some of your listeners, whether they be patients who would be willing to participate, providers, healthcare providers who have patients with these problems, just send them our way and participate. Because it's also really important that when you do a study that these studies enroll quickly. And the reason for that is that if a study enrolls very slowly, pharmaceutical companies, which at the end of the day are, do care about dollars and cents. If a study takes two years to enroll, they think that either there are not enough women who have the problem, or it's not bad enough that women are not willing to enroll in clinical trials. We've sort of brought the horse to the water and women aren't horses, but women need to drink. They have to participate. If they don't participate, all of this hard work, designing these, figuring out the causes and design these clinical trials and making these clinical trials available. If women don't sign up to participate, then it's actually going to make things go backwards because drug companies, pharma companies will say women are, it's just not a big enough problem. Women's health issues are not important.

[A]

That is so worth saying and thank you for saying that because I think there is kind of a learned helplessness. And I think what's trending on social media right now, now is like, nobody's studying anything right now. We don't know anything and nobody's studying it. And that really closes people's minds to like, no, there's stuff going on. We just got to communicate that. And I think you are brilliant for many reasons. But one is like getting on a podcast where 20,000 people are going to hear that. We've got very exciting vulvodynia and lichen sclerosis studies that are open for enrollment. Join now.

[B]

Well thank you and again vulvadina.com go to research tab and that you'll be able to see some of those. If you want to contribute to research either in cervical cancer or cancers, gynecologic cancers around the world, especially in resource poor countries, and also vulvar pain problems research, you can go to gyncancer.org, which is the Gynecologic Cancers Research foundation and that's my private foundation but also the National Vulva Denny Association. Tight Lipped are also great organizations where you can contribute to and they put their money towards research and patient advocacy.

[A]

Love it. Thank you so much for joining us today.

[B]

Thanks for having me. I really appreciate it.

[A]

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