Subtypes of Provoked Vestibulodynia
Condition: Provoked Localized Vulvodynia
MeSH terms: Vulvodynia; Vulvar Vestibulitis
Study type: Observational

Summary: 
      The proposed study will evaluate a clinical algorithm for the diagnosis and treatment of
      provoked vestibulodynia (PVD). The algorithm, distinguishes between four subtypes of PVD:
      hormonally mediated PVD, hypertonic pelvic floor dysfunction, congenital neuroproliferative
      PVD and acquired neuroproliferative PVD, based on a patient's history and physical exam. The
      study will follow patients diagnosed with PVD, for one year, and evaluate the treatment
      outcome in the different subgroups. Investigators hope that conducting a prospective study,
      showing clinical benefit and improved outcome for patients classified according to this
      method may change the common practice of "trial and error" based treatment, and will improve
      clinical results.
    

Detailed description: 
      Background Provoked vestibulodynia (PVD) is the term describing a syndrome of provoked,
      localized allodynia of the vestibule of the vulva, not explained by another condition, and
      lasting more than 3 months. PVD is not a defined disease but rather a symptom. It is thought
      that PVD represent a group of distinct disorders that have been classified together because
      they produce pain in the same anatomic location. Causes of these disorders include hormonal
      imbalance, mainly caused by hormonal contraception, nerve fiber proliferation in the
      vestibular mucosa and hypertonic pelvic floor dysfunction. PVD may appear with sexual debut
      or first attempts to insert a tampon (primary PVD) or can be a new onset of pain with
      activities that did not previously illicit pain (secondary PVD).

      Studies found that different factors such as genetic, inflammatory mediators, recurrent
      vaginitis, allergy and trauma may be involved in the development of PVD. A high percentage of
      patients with vulvar pain report an antecedent history of vulvovaginal candida infection,
      although it is unknown if this represents a true increase in incidence or a misdiagnosis. It
      has been suggested that repeated vulvovaginal infections are a triggering event for some
      women leading to chronic vulvar pain. This observation has led to hypothesis that in patients
      with neurogenic vulnerability, an initiating event or series of events may lead to chronic
      vulvar pain.

      Treatment of vulvodynia is generally predicated on a trial and error basis, because the
      pathogenesis is not defined. The result is that many forms of therapeutic interventions have
      been used, yet the evidence remains largely inconclusive, the response rate varies between
      40-85%, and many women do not respond to any of the treatments. Unfavorable outcomes to
      therapy can be explained by grouping patients with different conditions under one diagnosis,
      and then studying an intervention that might only help one subset of the conditions. This can
      lead to an apparent lack of effect, due to dilution of the patient subpopulations.

      A different approach to diagnosis and treatment of PVD was suggested by Dr. Andrew Goldstein.
      He classifies PVD into groups, based on history and examination findings:

        1. Hormonally mediated PVD - The pain began while taking hormonal contraceptive or other
           medications that affect hormones, after removal of ovaries, breastfeeding or menopause.
           Typically, patients have a low calculated free testosterone and complain of dryness and
           decreased libido. The entire vestibule is tender and vestibular mucosa is often dry and
           thin. Treatment includes stopping hormonal contraception and application of topical
           estradiol with testosterone to the vestibule.

        2. Hypertonic pelvic muscle dysfunction - In this subgroup, pelvic floor (PF) muscles
           become tight and tender. Patients often have other symptoms suggesting hypertonicity
           (urinary frequency, urgency and hesitancy, constipation, hemorrhoids and anal fissures),
           and predisposing factors, such as musculoskeletal disorders or anxiety may coexist.
           Typically, the pain is much worse at 4-8 o'clock position of the vestibule with minimal
           or no pain in the upper vestibule. Treatment includes PF physiotherapy, with an optional
           addition of muscle relaxants (valium suppositories and Botulinum toxin injections).

        3. Neuroproliferative PVD- In this condition, women have an increased number of nociceptors
           in the vestibular mucosa. This group is further subdivided into congenital and acquired
           forms. In the congenital subgroup, vestibular pain has always been present, and there
           may be sensitivity to palpation of the belly button (which is an evidence of a
           congenital neuronal hyperplasia within the tissue derived from the urogenital sinus).
           With acquired neuroproliferative PVD, the pain may begin after a severe allergic
           reaction or vaginitis. There is tenderness of the entire vestibule. Treatments include
           topical anaesthetics, antidepressants, antiseizure drugs, capsaicin cream and vulvar
           vestibulectomy.

      Goldstein's diagnostic algorithm is claimed to allow differentiation between different causes
      of PVD. In doing so, appropriate treatments to each subgroup can be selected, and their
      success rate should exceed the reported success rate in PVD treatment studies. Although
      investigators have a good personal experience with this method, the algorithm is not evidence
      based.

      Objectives:

      The proposed study is a prospective, cohort-based study, which will evaluate the
      characteristics of PVD-subgroups according to Goldstein's algorithm, patients' response to
      treatment and their outcome.

      General aims: Define whether women that have been diagnosed according to Goldstein's
      algorithm experience higher rates of favorable outcome in comparison to those reported in the
      literature. This will allow us to study the effectiveness of this classification and to
      better define the subgroups.

      Specific aims:

        1. Describe the population of women with PVD attending the clinic, the distribution of
           criteria and the characteristics of women in each category.

        2. Follow women diagnosed according to algorithm for one year and define treatment success.

      Methods The proposed study is a prospective, cohort-based study. Patients will be recruited
      from the clinic for vulvovaginal disorders in Clalit Healthcare services in Jerusalem. The
      diagnostic procedures, patients' sub-classification and the proposed treatments in the
      current protocol are identical to those currently used in the clinic. Patients who fulfill
      diagnostic criteria of PVD and who will be willing to participate in the study will be asked
      to sign an informed consent and complete self-administered intake questionnaires requesting
      data about their PVD condition and its severity, various parameters of quality of life (QOL),
      general health, Ob\Gyn history, sexual function, psychometric characteristics (anxiety,
      depression etc) and demographics. After completing the questionnaires, each patient will
      undergo a standard evaluation, and will be diagnosed according to Goldstein's algorithm.
      Instructions for treatment will be given in regards to the diagnosis. Patients will be
      instructed to schedule follow-up appointments at 3,6,9, and 12 months. During follow-up
      appointments they will be assessed in regard to vestibular tenderness using various
      parameters, as well as by questionnaires of QOL and sexual function.
    

Intervention name(s): Topical hormonal cream (estrogen); Pelvic floor physical therapy; Low Level Laser therapy
Intervention type(s): Drug; Procedure; Procedure
Intervention description(s): Patients will be instructed to stop hormonal contraception and to apply 0.1 ml topical cream containing 0.1% of estriol to the vestibule, once daily for 3 months; PF physical therapy once weekly for 3 months; non-thermal laser irradiation (low levels of red and near infrared light) is applied directly to the vestibule
Intervention MeSH terms: Estrogens
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients will be recruited from the clinic for vulvovaginal disorders in Clalit Healthcare
        services in Jerusalem.