Antifungal Appears to Ease Fungus-Culture-Negative Vulvodynia

By Reuters Staff

July 20, 2021

NEW YORK (Reuters Health) - In a pilot study, treatment with the antifungal itraconazole was associated with a significant reduction in vulvovaginal pain in women with negative fungus cultures and no other identifiable disease, prompting the researchers to call for a randomized placebo-controlled confirmatory trial.

Vulvodynia - chronic, unexplained pain in the area around the opening of the vagina - is tough to treat due to both the uncertain cause of the disorder and poorly available therapies, the study team explains in a paper in Sexual Medicine.

Itraconazole has been proposed as a treatment for vulvodynia. To investigate further, Dr. Rodger Rothenberger of Penn State University College of Medicine and colleagues took a look back at 106 women with vulvodynia who were treated with itraconazole.

All of the women had been treated with up to 200 mg daily of fluconazole for six to eight weeks with insufficient reduction in vulvar pain and elected to initiate treatment with itraconazole. All of them had negative fungus cultures for more than two months before starting itraconazole.

For all 106 patients, the average reduction in pain was 61% by cotton-swab testing.

"Interestingly," say the researchers, pain reduction increased with duration of itraconazole therapy. Treatment for five or more weeks with a dosage of 400 mg of itraconazole (dispersed as 200 mg twice per day) was deemed the most effective, they report. Women who continued itraconazole for five to eight weeks saw a 70% reduction in pain.

Overall, more than a third of women (38%) had complete resolution of pain and 54% had a greater than 60% reduction in pain. A lack of symptom reduction was observed in 9% of the women; in 4%, an increase in pain was observed.

"To our knowledge this is the first report of a significant reduction in objectively tested vulvar pain associated with itraconazole treatment and is striking in its complete or almost complete amelioration of pain in a large percentage of patients," Dr. Rothenberger and colleagues write.

Addressing potential mechanisms, the authors note that itraconazole is recognized as an angiogenesis inhibitor and has been studied as a possible anticancer therapy.

The antifungal has been shown to decrease angiogenesis through action on the mTOR signaling pathway, specifically through mTORC1, which plays an active role in inflammation-related angiogenesis and nerve growth factor protein expression in Schwann cells.

That this could be important "is supported by the theorized mechanism for the induction of pain in vulvodynia patients that of infection and/or trauma causing an initial insult which induces inflammation, leading to angiogenesis, nerve fiber proliferation and chronic pain," they explain.

The researchers say randomized control trials with long-term follow-up to six to 12 months after treatment are needed to gauge itraconazole's impact on long-term remission, along with an examination of different doses of the drug.

"The implication that an organic and treatable cause exists for vulvodynia with an effective treatment would have substantial practice-altering implications,' the researchers conclude.

The study had no external funding and the authors have no relevant disclosures.

SOURCE: Sexual Medicine, online July 9, 2021.