Hormonal Contraceptive Use and the Risk of Provoked Vestibulodynia

NCT ID: NCT01741948

Last Updated: 2015-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2012-01-31

Study Completion Date

2013-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Vestibulodynia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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First time users of hormonal contraceptive

Hormonal contraceptive

Intervention Type DRUG

The study will follow patients who are first time users of HCs for a full year after initiation. Patients will be followed every 3 months via questionnaires, blood examinations, and gynecologic examination, in case dyspareunia evolves.

First appointment (before initiation of HCs):

Questionnaire FSFI (Female Sexual Function Index) questionnaire. Blood collection for hormones levels and extraction of mononuclear blood cells. A gynecologic exam intended to rule out existing problem which causing dyspareunia.

3,6,9,and 12 months after initiation of HCs or anytime if a patient has dyspareunia:

Questionnaire evaluating possible influence of HCs use (dyspareunia, lubrication and libido).

FSFI questionnaire. Blood collection Gynecologic examination, designated to assess the cause of pain, including assessment of vestibular tenderness, muscle tightness and tenderness, pressure-pain thresholds measurement using vulvar algesiometer, pH measurement and vaginal swab for microscopy.

Interventions

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Hormonal contraceptive

The study will follow patients who are first time users of HCs for a full year after initiation. Patients will be followed every 3 months via questionnaires, blood examinations, and gynecologic examination, in case dyspareunia evolves.

First appointment (before initiation of HCs):

Questionnaire FSFI (Female Sexual Function Index) questionnaire. Blood collection for hormones levels and extraction of mononuclear blood cells. A gynecologic exam intended to rule out existing problem which causing dyspareunia.

3,6,9,and 12 months after initiation of HCs or anytime if a patient has dyspareunia:

Questionnaire evaluating possible influence of HCs use (dyspareunia, lubrication and libido).

FSFI questionnaire. Blood collection Gynecologic examination, designated to assess the cause of pain, including assessment of vestibular tenderness, muscle tightness and tenderness, pressure-pain thresholds measurement using vulvar algesiometer, pH measurement and vaginal swab for microscopy.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Hadassah Medical Organization

OTHER

Sponsor Role collaborator

ahinoam lev sagie

OTHER

Sponsor Role lead

Responsible Party

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ahinoam lev sagie

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ahinoam LevSagie, MD

Role: PRINCIPAL_INVESTIGATOR

Clalit Health Services

Locations

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Clalit health Services

Jerusalem, , Israel

Site Status

Hadassah Medical Organization

Jerusalem, , Israel

Site Status

Countries

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Israel

References

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Goldstein A, Burrows L, Goldstein I. Can oral contraceptives cause vestibulodynia? J Sex Med. 2010 Apr;7(4 Pt 1):1585-7. doi: 10.1111/j.1743-6109.2009.01685.x. Epub 2010 Jan 25.

Reference Type BACKGROUND
PMID: 20102483 (View on PubMed)

Greenstein A, Ben-Aroya Z, Fass O, Militscher I, Roslik Y, Chen J, Abramov L. Vulvar vestibulitis syndrome and estrogen dose of oral contraceptive pills. J Sex Med. 2007 Nov;4(6):1679-83. doi: 10.1111/j.1743-6109.2007.00621.x.

Reference Type BACKGROUND
PMID: 17970976 (View on PubMed)

Bohm-Starke N, Johannesson U, Hilliges M, Rylander E, Torebjork E. Decreased mechanical pain threshold in the vestibular mucosa of women using oral contraceptives: a contributing factor in vulvar vestibulitis? J Reprod Med. 2004 Nov;49(11):888-92.

Reference Type BACKGROUND
PMID: 15603099 (View on PubMed)

Bouchard C, Brisson J, Fortier M, Morin C, Blanchette C. Use of oral contraceptive pills and vulvar vestibulitis: a case-control study. Am J Epidemiol. 2002 Aug 1;156(3):254-61. doi: 10.1093/aje/kwf037.

Reference Type BACKGROUND
PMID: 12142260 (View on PubMed)

Sjoberg I, Nylander Lundqvist EN. Vulvar vestibulitis in the north of Sweden. An epidemiologic case-control study. J Reprod Med. 1997 Mar;42(3):166-8.

Reference Type BACKGROUND
PMID: 9109085 (View on PubMed)

Bazin S, Bouchard C, Brisson J, Morin C, Meisels A, Fortier M. Vulvar vestibulitis syndrome: an exploratory case-control study. Obstet Gynecol. 1994 Jan;83(1):47-50.

Reference Type BACKGROUND
PMID: 8272306 (View on PubMed)

Johannesson U, Sahlin L, Masironi B, Hilliges M, Blomgren B, Rylander E, Bohm-Starke N. Steroid receptor expression and morphology in provoked vestibulodynia. Am J Obstet Gynecol. 2008 Mar;198(3):311.e1-6. doi: 10.1016/j.ajog.2007.09.041. Epub 2008 Feb 21.

Reference Type BACKGROUND
PMID: 18177837 (View on PubMed)

Johannesson U, Sahlin L, Masironi B, Rylander E, Bohm-Starke N. Steroid receptor expression in the vulvar vestibular mucosa--effects of oral contraceptives and menstrual cycle. Contraception. 2007 Oct;76(4):319-25. doi: 10.1016/j.contraception.2007.06.014. Epub 2007 Aug 28.

Reference Type BACKGROUND
PMID: 17900445 (View on PubMed)

Johannesson U, Blomgren B, Hilliges M, Rylander E, Bohm-Starke N. The vulval vestibular mucosa-morphological effects of oral contraceptives and menstrual cycle. Br J Dermatol. 2007 Sep;157(3):487-93. doi: 10.1111/j.1365-2133.2007.08066.x. Epub 2007 Jul 11.

Reference Type BACKGROUND
PMID: 17627793 (View on PubMed)

Eva LJ, MacLean AB, Reid WM, Rolfe KJ, Perrett CW. Estrogen receptor expression in vulvar vestibulitis syndrome. Am J Obstet Gynecol. 2003 Aug;189(2):458-61. doi: 10.1067/s0002-9378(03)00365-x.

Reference Type BACKGROUND
PMID: 14520218 (View on PubMed)

Harlow BL, Vitonis AF, Stewart EG. Influence of oral contraceptive use on the risk of adult-onset vulvodynia. J Reprod Med. 2008 Feb;53(2):102-10.

Reference Type BACKGROUND
PMID: 18357801 (View on PubMed)

Harlow BL, Stewart EG. A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? J Am Med Womens Assoc (1972). 2003 Spring;58(2):82-8.

Reference Type BACKGROUND
PMID: 12744420 (View on PubMed)

Other Identifiers

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Levsagie OCP PVD

Identifier Type: -

Identifier Source: org_study_id

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