Hormonal Contraceptive Use and the Risk of Provoked Vestibulodynia
Hormonal Contraceptive Use and the Risk of Provoked Vestibulodynia
There have been reports in the medical literature demonstrating a link between the
 development of provoked vestibulodynia (PVD), a sexual pain disorder, and hormonal
 contraceptive (HC) use. The purpose of this pilot study is to assess the prevalence of HCs
 induced PVD among a HC naïve population, to evaluate which of the components of the HCs are
 associated with a higher risk of the development of PVD, and to evaluate which clinical and
 genetic factors predispose the patient to HCs induced PVD. Assessments will be made through
 patient questionnaires, physical examinations, and blood tests. Microarray techniques will be
 employed to characterize, on a global level, the gene expression profiles of women who
 develop PVD in comparison to those who do not develop PVD. Patients will be followed for a
 year. Results will be used to develop a larger clinical trial.
Background:

 Provoked vestibulodynia (PVD), previously called vulvar vestibulitis syndrome, is clinically
 defined as chronic, unexplained, vulvar pain or discomfort, confined to the vulvar vestibule,
 in response to contact or pressure. As a result, women with PVD experience pain on sexual
 intercourse, and many patients also have pain in response to non-sexual activities. The
 actual prevalence of PVD is unknown, but current evidence indicates that the lifetime
 cumulative incidence of vulvodynia approaches 15%. Currently, PVD is thought to be the
 leading cause of dyspareunia in premenopausal women. Once a woman with PVD develops the
 syndrome, symptoms may last for years; as a result, PVD has a profound effect on women's
 sexuality and psychological well-being.

 The diagnosis of PVD is usually made by assessing for the presence of the modified
 Friedrich's criteria. These criteria consist of 1) a history of vulvar pain, dyspareunia or
 pain with tampon insertion, 2) tenderness of the vestibule when being touched with a
 cotton-tip applicator, and 3) no other identifiable cause for the pain (such as vaginitis,
 dermatitis etc.).

 The etiology of this condition remains unknown. Proposed causes include chronic inflammation,
 peripheral neuropathy, genetic, immunologic and\or hormonal factors, infection, psychological
 disorders, sexual dysfunction, or disturbance in the central nervous system.

 Several studies have demonstrated an increased risk of developing PVD secondary to hormonal
 contraceptive (HC) usage. The relative risk of developing PVD seems to rise with an increased
 duration of HCs use (at least up to 2-4 years of use), first use of HCs at a young age (<16
 years), and the hormonal composition of HCs, specifically the progestogenic, estrogenic, and
 androgenic potency of the pills.

 Several mechanisms of action have been suggested for HCs induced PVD:

 -  Alteration of vestibular hormonal receptors.

 -  Alterations of the morphological pattern of the vestibular mucosa(13).

 -  Decreased pain threshold.

 -  Alteration of serum free hormones levels.

 Objectives/Purpose of the Study:

 1. To assess the actual prevalence of HCs induced PVD in a prospective study.

 2. To evaluate which of the components contained in the HCs (oral contraceptives,
 transdermal patch, vaginal ring) are associated with higher risk of HCs induced PVD,
 specifically; the dose of ethinyl estradiol (15, 20 and 30 mcg) and the progesterone
 component.

 3. To evaluate which factors predispose the patient to HCs induced PVD. We will analyze
 both clinical (age, age at menarche, length of use, body mass index etc.), hormonal (E2,
 testosterone etc.) and altered gene expression factors.

 The proposed study is a preliminary investigation aimed at estimating the rate of HCs induced
 PVD. The data from this study will enable the determination of the number of patients needed
 to obtain statistical significance in a future, larger study regarding patients' risk factors
 for developing PVD and HCs formulation.

 For this pilot study the investigators will evaluate 200 patients and follow them for a total
 of 1 year after HC initiation. Since this is a novel study that has not been investigated,
 nor is there available statistics in the medical literature, the investigators anticipate
 that 200 patients will provide enough data regarding incidence of PVD development secondary
 to HCs use.

 Definitions and measures to be used to diagnose HC induced PVD:

 1. New onset of vulvar pain suggestive of PVD, i.e. symptoms of pain on vaginal penetration
 (insertional dyspareunia and/or pain with tampon insertion), following initiation of
 HCs.

 2. On exam, tenderness localized within the vestibule when being touched with a cotton-tip
 applicator. The exam will be performed on defined points of the labia minora, labia
 majora and the vestibule in 5 defined points (1,5,6,7,11), with patients reporting pain
 verbally by a rating scale of 0 to 10 at each point.

 3. No identifiable cause for the pain, such as vulvovaginal candidiasis, desquamative
 inflammatory vaginitis (DIV), herpes, dermatitis or vulvar dystrophy.

 Time frame for completion: The investigators anticipate one year for patients' enrollment and
 another year for follow up. Data analysis and microarray analyses will be done during the
 third year. Data should be available within 3 years of study initiation.
Inclusion Criteria:

 -  200 non pregnant women between 18-35 naïve to HCs or other hormonal medications.

 -  Patients able to provide Informed Consent and complete questionnaires.

 -  Patient intends to use HCs for at least one year.

 -  On exam before initiation of HCs, patient does not have primary PVD, pelvic floor
 hypertonicity, vaginismus or congenital abnormalities.

 -  Patient will be available for follow up appointments.

 -  Patient is willing to undergo gynecologic examination, if dyspareunia develops.

 Exclusion Criteria:

 -  Patients with endocrine disturbances (including PCOS), liver diseases and eating
 disorders.

 -  Patients who suffer from Hypertension, Migraine with aura or clotting disturbances.

 -  Patients that experience pain with intercourse or tampon insertion.

 -  Patients that have other contraindications for HCs use