ABSTRACT: Vulvodynia, a common cause of dyspareunia, inflicts physical pain and emotional distress in 16% of women during their lifetime. Symptoms include burning, knife-like pain or pain on contact in the vulvar area for at least 3 months. The etiology of this condition is unclear, and acceptable diagnostic criteria are subjective. Treatment is empirical. A recent review reported success rates for medical treatments ranging from 13% to 67%. Few randomized treatment trials have been conducted. Two previous studies reported that vestibular tissues from women with localized provoked vulvodynia (LPV) when compared with healthy women showed a significant increase in vestibular mast cells, heparanase activity, and intraepithelial neuroproliferation. Data suggest that mast cell heparanase degrades and weakens the structural integrity of the vestibular stroma, resulting in penetration of nerve fibers through the epithelial basement membrane and vestibular hyperinnervation. Enoxaparin, a low-molecular-weight heparin (LMWH), is a strong inhibitor of heparanase activity. Some investigators have suggested that enoxaparin treatment may strengthen the vestibular stroma and prevent neuroproliferation in women with vulvodynia.
This randomized, double-blind, placebo-controlled study evaluated the effectiveness of enoxaparin for treatment of LPV. Forty women (aged 19–39 years) with severe LPV were randomized to receive either enoxaparin (n = 20) or placebo (n = 20). Clinical pain scores and local vulvar sensitivity were compared before treatment, at the end of treatment, and at the end of the study 3 months later. The effect of treatment on the number of vestibular mast cells, heparanase quantification, and neuroproliferation was measured by comparing immunostaining of biopsied tissue taken from the most painful focus at the beginning of the study with those taken from a parallel vestibular site at the end of the study.
There was a significantly greater reduction in vestibular sensitivity in the enoxaparin group than in the placebo group at the end of the study (29.6% vs 11.2%, respectively; P = 0.004). At the end of the study, 75% (15/20) of women in the treated group reported more than 20% pain reduction compared with 27.8% (5/18) in the placebo group (P = 0.004). Seven women in the enoxaparin group and 3 in the placebo group reported nearly painless intercourse at the end of the study. Among the women with improved sensitivity at the site parallel to the original biopsy site, a histologically documented reduction was found in the number of intraepithelial-free nerve fibers in the enoxaparin group.
These findings show that enoxaparin treatment reduces neuroproliferation concomitant with a reduction in vestibular sensitivity and dyspareunia among patients with LPV.
From the Department of Obstetrics and Gynecology (Y.F., D.Z., L.A., A.L., J.B.), Western Galilee Hospital, Bar-Ilan Faculty of Medicine, and the Pathology Department, Western Galilee Hospital, Nahariya, the Sex Therapy Clinic, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel