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VestibulodyniaNCT01741948

Hormonal Contraceptive Use and the Risk of Provoked Vestibulodynia

An observational study of Vestibulodynia, run by ahinoam lev sagie at 2 sites in Israel.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for
Vestibulodynia
What is being tested?
Hormonal contraceptive
How many people
0 participants
Where
2 sitesIsrael
Study dates
Jan 2012to Dec 2013
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Study population: The study will follow patients who are first time users of HCs for a full year after initiation. Patients will be recruited in a gynecology clinic affiliated with the "Clalit" Health Maintenance Organization in Jerusalem, Israel (Merkaz Briut Haisha, Ramat Eshkol, Jerusalem). This is a primary care government funded clinic, treating a diverse population.

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

Israel2 sites
  • Clalit health Services

    Jerusalem

  • Hadassah Medical Organization

    Jerusalem

Other trials in Israel

About this study

Official title: Hormonal Contraceptive Use and the Risk of Provoked Vestibulodynia- A Prospective Study

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.

Read the detailed description

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
Vestibulodynia
Being tested
Hormonal contraceptive
Keywords
Provoked vestibulodynia, Hormonal contraceptives
Medical subject headings
Vulvodynia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hormonal contraceptiveDrug

    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.

Study groups in NCT01741948
Study groupRoleWhat they receive
First time users of hormonal contraceptiveNot described
Receives: Drug: Hormonal contraceptive

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence of hormonal-contraceptive induced provoked vestibulodynia

    one year for patients' enrollment and another year for follow up.

    Measured: One year

Secondary outcomes (3)
  1. Hormonal contraceptive components associated with higher risk of HCs induced PVD

    Dose of ethinyl estradiol (15, 20 and 30 mcg) The progesterone component

    Measured: One year

  2. Clinical factors associated with HCs induced PVD

    Age at menarche Length of use Body mass index

    Measured: One year

  3. Biochemical markers associated with higher risk of HCs induced PVD

    Hormones: E2, testosterone Altered gene expression

    Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionDec 2013
  4. Study completionDec 2013

Why it stopped: the study has never started. my grant request was denied.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01741948
Sponsor's protocol ID
Levsagie OCP PVD
Status last verified
Feb 2015
First submitted
23 Nov 2012
Last updated
10 Feb 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 20102483
  • 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.

    PubMed 17970976
  • 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.

    PubMed 15603099
  • 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.

    PubMed 12142260
  • 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.

    PubMed 9109085
  • 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.

    PubMed 8272306
  • 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.

    PubMed 18177837
  • 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.

    PubMed 17900445
  • 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.

    PubMed 17627793
  • 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.

    PubMed 14520218
  • 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.

    PubMed 18357801
  • 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.

    PubMed 12744420

Questions about this trial

What is this clinical trial studying?

An observational study of Vestibulodynia, run by ahinoam lev sagie at 2 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 10 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of hormonal-contraceptive induced provoked vestibulodynia (time frame: One year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01741948, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2015.

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