Michael Krychman, MD

What are some of the challenges about diagnosing recurrent VVC [vulvovaginal candidiasis]? Do you think people are very aware in the community at large?

The first issue really, as far as diagnosis is concerned, is so-called self-diagnosis. This is the ability of any individual woman to be able to diagnose with great certainty that her symptoms are attributable to a yeast. Self-diagnoses are remarkably inaccurate. I know there’s always going to be some argument from the people listening in on this, participants hearing this, watching this video, but really there are numerous good objective studies that show just how unreliable self-diagnosis is. That doesn’t mean patients, women, don’t have symptoms, it simply means that the symptoms are entirely nonspecific. There’s nothing unique to the symptoms that says, “Oh, I obviously do have a yeast infection.” Repeatedly, women are referred to me because of recurrent candida vaginitis, and when I start interrogating and talking to them, and getting a history, and we do the appropriate tests, we find that there’s a lot of overdiagnosis of recurrent infections and there are some elements of underdiagnosis, especially for chronic disease. But you’ve already outlined the various symptoms involved, so the next issue, as far as diagnosis is concerned, it’s not difficult to diagnose once the patient finds herself visiting a practitioner, and this is not a telehealth visit. Telehealth is a wonderful advance in medicine and science, but in the diagnosis of vaginitis it’s about 10 steps backwards. You cannot diagnose reliably any form of vulvovaginal disease without seeing a practitioner who takes a history and does a good physical examination as well as the appropriate immediate local tests that are available within the doctor’s office.

I agree with you. The physical exam is invaluable and we’ll touch upon the concept of overdiagnosis, underdiagnosis in a little bit and how the impact of telehealth and teleprescribing, and you had mentioned that people are misdiagnosing or over the counter, we don’t have confirmation of diagnoses, so overdiagnosis. Every vaginitis is not yeast. Sometimes there’s BV [bacterial vaginosis]. Sometimes there’s a mixed infection. Sometimes it’s vulvovaginal atrophy. I think part of the issue that we are seeing is we have created this issue where there is a lot of telephone diagnosis and treatment because we didn’t have a choice with COVID-19, and then we’re overtreating. We’re seeing the emergence of resistance. We’re seeing more nonalbicans candidiasis. We’re seeing a variety of things that are changing in the landscape.

Videos

Michael L. Krychman, MD, and Jack D. Sobel, MD, review diagnostic criteria of diagnosis of RVVC and the impact of misdiagnosis.

The Challenges of Diagnosing Recurrent Vulvovaginal Candidiasis

Welcome to this Peers & Perspectives® presentation titled, “Expert Perspectives on Recurrent Vulvovaginal Candidiasis Management.” I’m Dr Michael Krychman, a clinical health professor from the University of California, Irvine, located in Orange County, California. It’s a pleasure today to be joined with Dr Jack Sobel from Wayne State University in Detroit, Michigan, to discuss considerations and strategies for the practical management of vulvovaginal candidiasis. Dr Sobel, welcome to our program today and let’s jump right in. I know that you and I both have renewed interest in vulvovaginal candidiasis. The landscape is changing. Before we go into that, let’s talk a little bit about the pathophysiology, the differences between sporadic and RVVC [recurrent vulvovaginal candidiasis]. How do you specifically define that? We want to talk about signs and symptoms, risk factors, and what have you; why don’t you get us started on that?

Thanks for introducing the subject, Michael. I think to obtain some sort of perspective of what recurrent disease is, we need to recognize that about 70% of women are going to have a vaginal yeast infection sooner or later during their reproductive years. We know that candida vaginitis is just so much less common in postmenopausal women, and it is very rare prior to puberty and onset of menses. Having said that, most women will have an occasional or sporadic attack, and that’s going to be about 80% to 90% of women will have an occasional, or what we call now, a sporadic attack. It may occur with a certain trigger, or it may occur spontaneously without any recognizable triggers. An example of a trigger for that sporadic attack may be recent exposure to an antibiotic given for influenza or for sinusitis, and often for a reason that you really didn’t need to get antibiotics in the first place. Probably half the episodes of sporadic attacks occur without a recognized triggering mechanism. That’s very important because sometimes patients just don’t identify, or physicians are unable to attribute a trigger in sporadic attacks. When we’re talking about recurrent infections, we’ve arbitrarily set this at 3 or more attacks per year, and this is a completely different ballgame. This is a world of repeated attacks, which can be 12 attacks a year. It really creates havoc in the life of a patient because they’re going from one attack to the other. They see practitioners on a regular basis. It has a very profound effect on their normal lives. They’re having symptoms repeatedly or chronically and it has a major impact on their normal, healthy sex lives and seemingly they are taking antifungal agents almost all the time.

You’re making a good point. Quality of life is certainly a big issue and there’s sexuality issues, relationship issues. You also talked about the medical economic implications of visiting the health care professional quite often. Their symptoms are quite distressing: the burning, itching, pain. Even vulvar and vaginal awareness, where they can’t even sit. For me, in my clinical practice, the impact of VVC and RVVC is astronomical and we have to move away from the concept of “just another yeast infection” as well, right? I appreciate what you’re saying in terms of the impact and, sometimes, lack of risk factors.

Michael L. Krychman, MD and Jack D. Sobel, MD, talk about the signs and symptoms of vulvovaginal candidiasis as well as its effect on patient quality of life.

Pathophysiology and Impact of Vulvovaginal Candidiasis

The 2022 International Society of the Study of Women’s Sexual Health conference (ISSWSH) was recently held in-person in Dallas, Texas. While COVID-19 restrictions were still in place, sex researchers, sexual medicine professionals, counselors, physical therapists, and up and coming students all converged to attend this sexual medicine conference. 

The health care professionals (HCP) from Ms. Medicine, a national group of internists and primary care providers who are dedicated to comprehensive primary, gynecological, sexual, and menopausal health for women, were also well represented at this exciting conference. Here are some of the top takeaways from ISSWSH 2022.

Rachel Rubin, educational chair of ISSWSH, reinforced that the society and its researchers, scholars, and presenters were still working on understanding basic sexual anatomy and physiology for women. 

Compelling new data, adding to the growing research, indicated that the pelvic nerve and autonomic system may be innervating the vestibule and not just the pudendal area. Some new insights marked a novel understanding of the “G-ZONE of pleasure” that includes prostate-like tissue in the anterior vaginal wall. The cervix is triply innervated including innervation from the vagus nerve. “New insights to female sexual anatomy has far reaching implications for informed consent and surgical outcomes.” stated Rubin.

Shari B. Goldfarb, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, New York, hit a huge homerun at the conference with her presentation on breast cancer and flibanserin. 

During her data presentation, Goldfarb said flibanserin (Addyi; Sprout Pharmaceuticals) improves libido in breast cancer patients. This data was the game changer for this conference, as it sheds new light for this often misunderstood and underutilized medication. 

While flibanserin is approved for generalized acquired hypoactive sexual desire disorder (HSDD) in premenopausal women, its use in cancer patients remains off label and unapproved, yet promising. 

The preliminary results were as follows: 20 women with stage 0-III ER positive breast cancer on endocrine therapy for at least 3 months were enrolled and had close surveillance. Seventy percent of study subjects were able to complete the 24-week trial and took 80% of planned doses. 

Patients reported improved libido through patient-reported outcomes and satisfying sexual events (SSE) measures. The mean baseline Female Sexual Function Index score was 13.3 and desire score of 1.96, increased to 19.4 and 3.3 by 3 weeks of flibanserin use. Patient distress also decreased from 32 to 25 on the female sexual distress scale-revisedscale. 

While larger randomized, placebo-controlled clinical trials are needed to confirm this small study, the results show excellent promise in both safety and tolerability for HSDD treatment of the breast cancer patient with flibanserin. This is encouraging news for our breast cancer survivors who often suffer in silence with hypoactive sexual desire disorder (HSDD).

Sheryl Kingsberg, PhD, division chief of OB/GYN Behavioral Medicine at University Hospitals Cleveland Medical Center in Cleveland, Ohio, presented on “Women and Healthcare Professionals’ Understanding of their Concerns of Birth Control Side Effects.” 

Certainly, birth control has several benefits and risks that can be perceived differently by women and their HCPs. Kingsberg and her team sought to research specific side effects that women are most concerned with when choosing a birth control method, as well as the side effects that HCPs believe women want to know about when choosing a method of birth control. 

Sixty-five percent of the women who responded (n=121) stated they had turned down a method of birth control suggested to them by their HCP in the past. Forty percent of women reported side effects and tolerability issues as reasons for rejecting a birth control method. 

Adverse events included but were not limited to weight gain, infection, pain/discomfort, migration (arm implant), skin irritation, cramps, heavy and/or irregular periods, depression, and acne. 

Some HCPs believe that women may be making assumptions about side effects based on what they hear from friends and social media. HCPs perceive most side effects to be less concerning to women than they are–indicating a major disconnect. These results indicated that there is a gap in the appreciation by HCPs and what women are concerned about as it relates to the side effects of birth control. Women are much more concerned about blood clots, headaches, dizziness, libido, and nausea than HCPs perceive them to be.

Jim Pfaus, PhD, professor of neuroscience and psychology in the Department of Psychology and Life Sciences at Charles University, Prague, Czech Republic; and researcher at the Czech National Institute of Mental Health, presented preliminary findings on physiological arousal and orgasm with a sample of 54 women who used the Lioness “Smart” device with advanced biofeedback sensors designed to detect changes in sexual response via pelvic floor patterns. 

This novel study examined physiological responses of self-stimulation behavior outside of a laboratory setting and in a real-world setting. Further research like this could pave the way for future opportunities to study the relationship between physiological sexual response with other health related factors such as health conditions like heart disease or contraindications of prescription medications. 

HCPs could also potentially recommend this device to individuals who have concerns or queries about their own sexual pleasure, or to those who are curious to monitor and track changes in their own unique sexual responses. 

Individuals could then potentially use the data to recontextualize their sexual pleasure from something intangible or even shameful, to just another aspect of their body’s natural function.

The electronic computer-based poster session also created another opportunity for information exchange between the participants. Alisar Zahr, PhD, director of research and clinical development at Revision Skincare, presented late breaking data during the posters. 

The presented posters included research on a novel formulated vulvar moisturizer to target unmet gynecological and aesthetic needs, and preliminary results from an investigational post-shave cream. This was Revision Skincare’s debut in a gynecological/sexual medicine forum. 

The nonhormonal vulvar moisturizer demonstrated consumer acceptance in all self-assessment categories, product characteristics, skin perception, and overall satisfaction for both the vulvar area and in post shave use. Launch of this product is anticipated in 2022 or early 2023.

Alyssa Dweck, MD, MS, FACOG, chief medical officer at Bonafide Health, conducted a national survey of over 3000 Revaree (hyaluronic acid vaginal dryness suppository) users to assess patient satisfaction and use trends of the product. Women saw a highly significant reduction in dryness, irritation, burning, and pain with sex. 

Study participants saw highly significant satisfaction in ease of use, nonmessy insert, convenience, and improvement in quality of life with Revaree use. Total satisfaction with the product was 80%, (58% saw improvement in just 2 weeks of use and 85% saw improvement in 8 weeks). 

Ninety-six percent of users plan to continue using the product and 92% of users would recommend to others. These findings were consistent across a wide age range.

While presenters were masked and attendees were still social distancing, Kingsberg and her academic team’s poster assessed COVID-19’s impact on partner relationships, sexual activity, family planning, and menopause management. 

Her innovative poster demonstrated that 46% of reproductive-age women and 62% of menopausal women reported having sex at the same frequency as before the pandemic. Of the reproductive-age women, 27% reported having sex more frequently and 22% less frequently. Among menopausal women, 10% reported having more sex, and 17% reported having less frequent sex than before the pandemic. 

Those having more sex noted starting vaginal health products, that allowed more comfortable sex, helped with libido, and gave more free time and bonding with their partner. The authors reiterated that the COVID-19 pandemic has impacted women differently depending on their reproductive or menopause status including their relationships with their partners, sexual activity, family planning, and use of birth control or hormone therapy.

Not all the excitement was in the lecture hall. The hustle and bustle as well as medical buzz of the professional exhibits kept the participants continually engaged. Soul Source’s Owner and CEO, Jane Silverman certainly would win the ISSWSH Humanitarian award if there ever was one created. Participants appreciated the value of the company’s colorful and well designed, multi-sized dilators and sets for their patients, but are becoming increasingly impressed with Soul Sources continued community support. 

Soul Source recently donated community silicone dilators to Harvard Mass General’s sexual health program for their newly diagnosed patients. Jane has also worked to help refugees from Darfur with employment opportunities. Jane, known as the “dilator lady” has collected and donated supplies to urogynecologists in Africa who are preforming fistula repair. In addition, she has walked the exhibit halls collecting undistributed lubricant samples from exhibitors to include with her donations.

Dilators and devices appeared to certainly dominate the exhibit hall, Materna Medical displayed 2 products for pelvic floor conditions at ISSWSH this year—Milli and Prep. Milli is an expanding vaginal dilator which received marketing authorization from FDA in December 2021 to help relieve the symptoms of vaginismus and related dyspareunia. Prep is currently in a pivotal trial seeking to reduce pelvic floor injury during childbirth.

Another crowded booth was newcomer Pacific Roots in the exhibit hall. Their CBD products and suppositories were developed by US trained professionals specializing in pelvic pain (as an alternative to narcotic/valium suppositories). The suppositories are made in a US-certified compounding pharmacy and are third party tested for quality and purity. The suppositories contain magnesium, which is assumed to aid with muscle relaxation.

Bonafide Health added to their women’s health offering and unveiled their new probiotic at the ISSWSH conference. While blockbusters like Relizen (menopausal hot flashes), Ristela (sexual satisfaction), and Revaree (Vaginal dryness) still draw crowds to the Bonafide Health exhibit, newcomer Clairvee, a novel oral capsule in capsule probiotic for vaginal health, made its debut. 

Clairvee specifically targets vaginal health and shown to be safe and effective in four randomized placebo-controlled trials. It contains a probiotic blend of lactobacilli and a prebiotic lactoferrin.

Not all probiotics, however, are created equal. Randomized clinical trials support Clairvee, which reduces symptoms (discharge and itching) and reduces the recurrence of bacterial vaginosis and vulvovaginal candidiasis in those prone. Clairvee is uniquely administered monthly 15 consecutive days on and 15 days off, with studies suggesting persistence of lactobacilli strains in the vagina during the off time. Ongoing further research will certainly add to the existing data.

It was a pleasant surprise that while not specifically presenting data or exhibiting at the meeting, the representatives from Myovant, the makers of Myfemmbree (relugolix, estradiol, norethisterone acetate)approved for uterine fibroids and have a PDUFA date for May 2022 concerning a possible indication for endometriosis, were interested in women’s sexual function and quality of life considerations. Scynexis, makers of Brexafemme (ibrexafungerp), a first in class nonazole fungicidal treatment for vulvovaginal candidiasis, were also in attendance.

It is refreshing to note that the pandemic has not squelched female sexual health research or zeal for information exchange. Even pharmaceutical companies have recognized the importance of female sexual health and wellness, and are now placing much importance on quality of life and sexual health concerns for their female patients.

Michael L. Krychman, MD, is a consultant for Revision SkinCare, Materna and Scynexis. He is a researcher in the on-going JDS clinical trial (NCT04544475).

Articles

New frontiers in sexual medicine

Podcasts

In this episode of Pap Talk, Gloria Bachmann, MD, MSc, breaks down what it means to be a health care provider for incarcerated individuals, and explores the specific challenges women and their providers face during and after incarceration. Joined by sexual health expert Michael Krychman, MD, Bachmann also discusses trauma-informed care and how providers can get informed. 

Caring for women who are or have been incarcerated: contraception, sexual health, and trauma-informed care

Michael Krychman, MD, is a sexual health specialist and expert in survivorship medicine at the Southern California Center for Sexual Health and Survivorship Medicine.

Barb Dehn, NP, is a women’s health nurse practitioner at El Camino Women’s Group and a nationally recognized health expert who specializes in pregnancy, breastfeeding, fertility, menopause, and sexual health.

The following interview was conducted at the North American Menopause Society 2021 Annual Meeting from Sept. 22-25 in Washington, D.C.

I wanted to talk to Nurse Barb about one of the exciting opportunities to learn more about [vulvovaginal candidiasis (VVC)]. This has really been a stagnant field for a very long time, and I know there's a new medication that just came out. You're the go-to gal for what's new and exciting, so tell us more about what's new in a humdrum, older condition that we haven't really thought about much.

So VVC, vulvovaginal candidiasis. You and I both know, it's not just a yeast infection. Now, we may see this day in and day out. But for women, they're really suffering and there's a lot of impact. For the first time, though, we have a fungicidal medication, not fungistatic, which all the -azoles are. anything that ends in -azole is fungistatic, not fungicidal. Most clinicians are really surprised to learn that. So Brexafemme was just approved by the FDA. The generic name is ibrexafungerp. It's a fungicidal medication with excellent efficacy at 10 days, but also sustained efficacy at 25 days.

I've looked at the data, and I'm really excited about this 9-to-1 tissue penetration. Any thoughts about that?

Yes, that's amazing, isn't it? So with all of the -azoles, the tissue penetration is about the same as what you have in serum, so it's 1 to 1, but with Brexafemme, there's 9 times as much Brexafemme in the vaginal tissue as there is in serum. Also, and this is probably going to interest you, it works on a lower pH at less than 4.5. So that's really helpful for us. It also has a longer half-life of 20 hours. We don't know, but maybe that's why it has sustained efficacy.

In this video, Barb Dehn, NP, discusses Brexafemme, the first fungicidal medication approved for the treatment of vulvovaginal candidiasis. 

First fungicidal medication for VVC approved by the FDA

 for a full transcript and video of this episode. 

More coverage from NAMS Annual Meeting can be 

In this episode, Michael Krychman, MD, sat down with Alyssa Dweck, MD, gynecologist, and Bonafide medical advisor to catch up at this year's North American Menopause Society (NAMS) Annual Meeting.