Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis: Design, Development and Place in Therapy.

Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.

Topical Treatment of Recurrent Vulvovaginal Candidiasis: An Expert Consensus.

Background: Recurrent vulvovaginal candidiasis (RVVC), defined as three or more confirmed infections over 1 year, occurs in up to 10% of women. In these women, the objective is often symptomatic control rather than mycologic cure. Current Centers for Disease Control and Prevention (CDC) guidelines recommend oral fluconazole as first-line maintenance, but state if this oral regimen is not feasible, intermittent topical treatments can be considered. No specific recommendations for type or frequency of topical applications are provided by the CDC. Methods: A panel of vulvovaginal experts convened to develop a consensus recommendation for topical maintenance dosing for RVVC. Results: Data suggest that clotrimazole, miconazole, terconazole, and intravaginal boric acid are suggested recommendations for recurrent vulvovaginitis caused by both Candida albicans and nonalbicans species. Nystatin ovules may not be as effective as azoles. Identification of species will influence treatment decisions. In addition, treatment may be modified based on prior response to a specific agent, especially in nonalbicans species. Fluconazole, ibrexafungerp, and intravaginal boric acid should be avoided during pregnancy. Conclusions: The expert consensus for women with RVVC is an initial full course of treatment followed by topical maintenance beginning at one to three times weekly, based on chosen agent. Twice a week dosing was the regimen most often utilized. In some women, episodic treatment may be used, but maintenance should remain an option for this population.

The genitourinary syndrome of menopause.

ABSTRACT: Genitourinary syndrome of menopause (GSM) refers to a collection of symptoms resulting from diminished hormonal, primarily estrogenic stimulation to the vulvovaginal or lower urinary tract and may affect up to 50% of postmenopausal women. Symptoms, which are typically progressive and unlikely to resolve spontaneously, may include, but are not limited to, vulvovaginal dryness, burning or irritation, dyspareunia, or urinary symptoms of urgency, dysuria or recurrent urinary tract infection. These symptoms are typically progressive and unlikely to resolve spontaneously. Diagnosis is clinical. Telemedicine may play a role in diagnosis, initiation of treatment, and follow-up of women with GSM. Effective treatments include moisturizers and lubricants, local hormonal therapy with estrogen or dehydroepiandrosterone, and oral selective estrogen receptor agonists. Laser or radiofrequency procedures, although currently utilized, are being studied to comprehensively understand their overall effectiveness and safety. Additionally, the influence and effect of the vaginal microbiome, as well as potential of treatment via its manipulation, is being studied. We performed a literature search of PubMed, Google Scholar, and Ovid with search terms of vulvovaginal atrophy and GSM and reviewed major US Society Guidelines to create this narrative review of this topic. The literature suggests that healthcare providers can make a significant impact of the health and quality of life of women by being proactive about discussing and providing interventions for GSM. A systematic approach with consideration of current guidelines and attention to developing protocols for interventions should be employed.

Video Summary:http://links.lww.com/MENO/A702 .

Effect of gabapentin on sexual function in vulvodynia: a randomized, placebo-controlled trial.

BACKGROUND: Sexual dysfunction is common in women with vulvodynia. OBJECTIVE: The purpose of this study was (1) to evaluate whether extended-release gabapentin is more effective than placebo in improving sexual function in women with provoked vulvodynia and whether there is a relationship between treatment outcome and pelvic pain muscle severity that is evaluated by palpation with standardized applied pressure and (2) to evaluate whether sexual function in women with provoked vulvodynia would approach that of control subjects who report no vulvar pain either before or after treatment. STUDY DESIGN: As a secondary outcome in a multicenter double-blind, randomized crossover trial, sexual function that was measured by the Female Sexual Function Index was evaluated with gabapentin (1200-3000 mg/d) compared with placebo. Pain-free control subjects, matched by age and race, also completed Female Sexual Function Index for comparison. RESULTS: From August 2012 to January 2016, 230 women were screened at 3 academic institutions, and 89 women were assigned randomly to treatment. Gabapentin was more effective than placebo in improving overall sexual function (adjusted mean difference, 1.3; 95% confidence interval, 0.4-2.2; P=.008), which included desire (mean difference, 0.2; 95% confidence interval, 0.0-3.3; P=.04), arousal (mean difference, 0.3; 95% confidence interval, 0.1-0.5; P=.004), and satisfaction (mean difference, 0.3; 95% confidence interval, 0.04-0.5; P=.02); however, sexual function remained significantly lower than in 56 matched vulvodynia pain-free control subjects. There was a moderate treatment effect among participants with baseline pelvic muscle pain severity scores above the median on the full Female Sexual Function Index scale (mean difference, 1.6; 95% confidence interval, 0.3-2.8; P=.02) and arousal (mean difference, 0.3; 95% confidence interval, 0.1-0.6; P=.01) and pain domains (mean difference, 0.4; 95% confidence interval, 0.02-0.9; P=.04). CONCLUSION: Gabapentin improved sexual function in this group of women with provoked vulvodynia, although overall sexual function remained lower than women without the disorder. The most statistically significant increase was in the arousal domain of the Female Sexual Function Index that suggested a central mechanism of response. Women with median algometer pain scores >5 improved sexual function overall, but the improvement was more frequent than the pain domain. We hypothesize that gabapentin may be effective as a pharmacologic treatment for those women with provoked vulvodynia and increased pelvic muscle pain on examination.

Genitourinary syndrome of menopause: Common problem, effective treatments.

After menopause, about half of all women experience genital, sexual, and urinary symptoms associated with decreases in estrogen, termed genitourinary syndrome of menopause. First-line therapies are nonhormonal vaginal lubricants and moisturizers. For persistent symptoms, prescription estrogen in cream and ring formulations is effective.

Presenting symptoms among premenopausal and postmenopausal women with vulvodynia: a case series.

OBJECTIVE: The aim of the study was to determine whether there are differences in the clinical presentation of symptoms and vulvar pain ratings in postmenopausal women compared with premenopausal women with provoked vestibulodynia (PVD) enrolled in a clinical trial, after correcting for estrogen deficiency. METHODS: Questionnaire data were collected from 76 premenopausal and 24 postmenopausal women enrolled in a clinical trial for PVD. The questionnaire obtained information about the presence or absence of vulvar pain, the characteristics of this pain, and information about the women's demographic characteristics and reproductive health history. Participants were clinically confirmed to have PVD by a positive cotton swab test on pelvic examination and either absence of or corrected vulvovaginal atrophy based on Ratkoff staining with less than 10% parabasal cells. Women completed a standardized questionnaire describing their vulvar symptoms and rated daily pain on a visual analog scale (0 = no pain to 10 = worse pain imaginable) from sexual intercourse, tampon insertion (as a surrogate measure of intercourse) and 24-hour vulvar pain for 2 weeks during the screening period. Pretreatment data were analyzed before pharmacologic intervention. Chi-square was used to determine differences between pre- and postmenopausal women in demographic characteristics and clinical presentation, and independent t tests were used to analyze pain ratings by (0-10) numeric rating scale (NRS). RESULTS: The average ages of premenopausal and postmenopausal women were (30.6 ±â€Š8.6 y) and (54.4 ±â€Š6.5 y), respectively. The groups significantly differed with regard to relationship status (P = 0.002) and race (P = 0.03), but did not differ in years of education (P = 0.49), income level (P = 0.29), or duration of symptoms (P = 0.09). Postmenopausal women reported significantly more vulvar burning (70.00% vs 43.42%, P = 0.03), but there were no differences in vulvar itching (20.00% vs 22.37%, P = 0.82), vulvar stinging (40.00% vs 36.84%, P = 0.79), vulvar aching (50.00% vs 63.16%, P = 0.28), and vulvar stabbing (60.00% vs 71.06% P = 0.34) or in mean number of symptoms (2.40 ±â€Š1.0 vs 2.37 ±â€Š1.4, P = 0.92). Of the 70 participants completing diaries and meeting tampon insertion pain, there were no significant differences in mean (±SD) NRS pain ratings of postmenopausal compared with premenopausal women for tampon insertion (5.66 ±â€Š1.93 vs 5.83 ±â€Š2.15, P = 0.77), daily vulvar pain (3.20 ±â€Š2.55 vs 3.83 ±â€Š2.49, P = 0.38) and sexual intercourse (6.00 ±â€Š2.53 vs 5.98 ±â€Š2.29, P = 0.98). CONCLUSIONS: Pre- and postmenopausal women with PVD have similar pain scores, and with the exception of a higher incidence of burning in postmenopausal women, similar presenting clinical symptoms. The statistical power of this conclusion is limited by the small number of postmenopausal women in the study. Further research on the vulvar pain experience of the older woman with PVD is warranted.