Subcutaneous botulinum toxin type A injections for provoked vestibulodynia: a randomized placebo-controlled trial and exploratory subanalysis
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Previous studies using botulinum toxin type A (BT) to treat provoked vestibulodynia (PVD) reported conflicting findings, possibly attributable to singular injections or low doses. We assessed PVD treatment effectiveness with high-dose single injections of BT (50 or 100 units) versus placebo, and then repeat BT 100 U injections over 6 months.
This was a randomized, double-blind, three-arm, placebo-controlled study with 33 PVD patients. BT 50 U (arm A), 100 U (arm B) or saline (arm C) were injected subcutaneously into the dorsal vulvar vestibulum and pain was assessed after 3 months. The investigation proceeded as an unblinded exploratory analysis, in which symptomatic patients received a BT 100 U injection. Symptomatic patients in arm C received a second BT 100 U injection at the 6-month visit. Symptoms were measured at 3-month cycles using: (1) cotton swab-provoked visual analogue scale (VAS), (2) von Frey filaments, and (3) Marinoff dyspareunia scale.
The three groups were comparable in terms of demographics and baseline clinical characteristics. Three months after the initial injection, no significant differences in pain were observed among the study arms, yet significant improvements occurred within all groups using the von Frey filaments test. Results from the exploratory analyses showed repeat injections of 100 U BT over 6 months led to significant pain reduction (VAS and von Frey filaments). Fifty-eight percent (7/12) of patients assessable after repeat injections were symptom-free or had ≥ 2 VAS reduction. Adverse events were minor and no serious adverse events occurred during the RCT or exploratory analysis.
PVD symptoms after one subcutaneous injection of BT (50 or 100 units) did not significantly differ compared to placebo, yet all three study arms experienced a reduction in pain 3 months after a single injection. Exploratory analyses indicated that repeat high-dose BT injections may significantly reduce pain over 6 months.
This trial was registered with the Swiss Medical Agency (reference number: 2007DR2102) in 2007.
KeywordsProvoked vestibulodynia Vulvodynia Botulinum toxin type A von Frey filaments Dyspareunia Sexual intercourse
Botulinum toxin type A
Randomized controlled trial
Visual analogue scale
We acknowledge the support of Dr. R. Bernhardt, Senior Manager Scientific Services, Allergan AG, Switzerland, for the supply of botulinum toxin type A without obligation or input into this clinical trial. We also acknowledge the support of Malgorzata Roos, PhD, Department of Biostatistics, University of Zurich for advice on statistical analyses, and pharmacist Dr. D. Fetz for managing the drug inventory and randomization process.
ID: data collection, analysis and manuscript writing. NG: protocol finalization, study initiation, and manuscript editing. MK: concept idea, study protocol, and manuscript editing. GPG: patient recruitment, and manuscript editing. JW: data analysis, and manuscript editing. DF: concept idea, and manuscript editing. MKF: concept idea, study protocol, data analysis, manuscript writing and editing. CB: study organization, reports to authorities (Swissmedic, KEK), data collection and analysis, and manuscript writing. MKF and CB contributed equally to the manuscript.
Compliance with ethical standards
Ethics approval and consent to participate
Study design was approved by Ethics Commission of Zurich (KEK-ZH StV 16/2005). All patients provided written consent to participate.
Availability of data and material
The datasets used and/or analyzed during this current study are available from the corresponding author on reasonable request.
Conflict of interest
The authors declare that they have no competing interests.
Disclosure of funding support
The drug botulinum toxin type A was provided free of charge by Allergan AG, Zurich, Switzerland. The role of Allergan AG was solely in provision of the medication. The company was not involved in the study design; data collection, analysis, or interpretation; writing of the report; or decision to submit the paper for publication.
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