Pelvic Pain in Women With Endometriosis
Condition: Endometriosis; Chronic Pelvic Pain
MeSH terms: Endometriosis; Pelvic Pain
Study type: Observational

Summary: 
      This study will examine pelvic pain associated with endometriosis and explore better
      approaches to treatment. In women with endometriosis, uterine tissue grows outside the
      uterus. Standard treatments - altering hormone levels to prevent endometrial tissue growth or
      surgically removing endometrial tissue - treat pelvic pain only temporarily. This study will
      investigate the role of sex hormones, immune chemicals, stress hormones, and genes in pelvic
      pain and determine how the nerve, muscle, and skeletal systems are involved in this pain.

      Women between 18 and 50 years of age who:

        1. have endometriosis and chronic pelvic pain, and

        2. have chronic pelvic pain without endometriosis, and

        3. have neither endometriosis nor chronic pelvic pain and are willing to have a tubal
           ligation (Healthy Volunteer group),

      may be eligible for this study. Candidates are screened with a questionnaire to obtain
      information about their pain and previous treatments and related medical or social issues.
      Participants will undergo the following tests and procedures:

        1. Medical history and physical examination, including pelvic exam, blood tests,
           urinalysis, and diaphragm fitting.

        2. Questionnaires about pain, quality of life, sexuality, psychological attitudes,
           spiritual experiences, and history of headache and depression.

        3. At-home monitoring for 4 to 6 weeks of pain symptoms, menstruation and spotting,
           medicines taken, and urine collections to test for "LH" surge. LH is the hormone that
           causes the ovary to release a mature egg.

        4. Pre-laparoscopy evaluation to include:

             -  Examination of menstrual blood collected in a diaphragm for 4 hours.

             -  Blood sampling to measure adrenal and pituitary hormones. For this test,
                corticotrophin-releasing hormone (CRH) is injected through an IV needle. Up to five
                blood samples are drawn, starting before the injection until 45 minutes after it.
                Blood is also collected at this time for genetic analysis.

             -  In-depth pain assessment to identify trigger points in muscles associated with
                pelvic pain, regions of skin sensitivity, and bone pain. Some women will undergo
                microdialysis, which uses an acupuncture-type needle to collect chemicals from two
                different muscles.

             -  Blood sampling twice a week for 1 month to measure changes in blood substances
                during the menstrual cycle.

             -  Blood sampling after the LH surge to measure progesterone levels.

             -  Cervicovaginal lavage (washing of the cervix with saline and collecting the fluid)
                to obtain secretions for research.

             -  Ultrasound of the ovaries and uterus. This examination uses a probe inserted into
                the vagina that emits sound waves that are used to form pictures of the internal
                structures. A small piece of uterine lining is also obtained for examination and
                research purposes.

             -  A visit with the members of the Pain and Palliative care service to evaluate the
                pain in anticipation of offering other treatments for pain after surgery.

             -  Surgery:

      CPP + Endo or CPP only: Laparoscopy to look for and remove endometrial tissue. This procedure
      is done under general anesthetic. A viewing instrument called a laparoscope is passed through
      an incision in the belly button to look for endometriosis. If it is found, two or more
      incisions are made in the abdomen for other instruments to remove the tissue. A small piece
      of uterine lining is also obtained for examination and research purposes.

      Healthy Volunteers: Laparoscopy to perform the tubal ligation. A tubal ligation, commonly
      known as "getting your tubes tied," is a surgical procedure for women to sterilize them. This
      procedure closes the fallopian tubes, stopping the egg from traveling from the ovary to the
      uterus and preventing sperm from reaching the fallopian tube to fertilize an egg. In a tubal
      ligation, fallopian tubes are cut, burned, or blocked with rings, bands or clips. The surgery
      is effective immediately. Tubal ligations are 99.5% effective as birth control. This
      procedure is done under general anesthetic. A viewing instrument called a laparoscope is
      passed through an incision in the belly button to perform a tubal ligation. Two or more
      incisions are made in the abdomen for other instruments to perform the procedure. During the
      laparoscopy, we will look for and remove endometrial tissue. A small piece of uterine lining
      is also obtained for examination and research purposes.

      -Follow-up evaluations. Two weeks after surgery, patients return to NIH to discuss the
      surgical findings and treatment options. Follow-up visits are then scheduled at 1, 3, and 6
      months after surgery to complete questionnaires and determine if the treatment is working.
      Blood samples are drawn at each visit.
    

Detailed description: 
      Chronic pelvic pain associated with endometriosis is poorly understood. This study is an
      effort to better understand pelvic pain and identify novel medical approaches for treating
      it. Endometriosis is a very common disease of women in their reproductive years, in which
      endometrial tissue grows outside the uterus. In a recent epidemiologic study, we have shown
      strong associations among endometriosis, fibromyalgia, and autoimmune disorders. Currently,
      it is believed that endometriosis causes chronic pelvic pain. Yet, some women with
      endometriosis do not have any pain and others have pain in areas unrelated to endometriosis
      disease location. The standard approaches to treating endometriosis pain have been to
      medically alter hormone levels to prevent endometriosis tissue growth or to surgically remove
      endometriosis lesions. Pelvic pain is only temporarily treated by either approach, which
      suggests that the current classification of pain, based on disease and treatment with
      hormones or surgery is not adequate. The feeling of pain involves many complex processes.
      Generally, women suffer more frequently from chronic, long-term, painful conditions than men.
      This suggests that women process pain differently because of differences in sex hormone
      levels and genes expressed in a sexually dimorphic fashion, as well as in central nervous and
      immune system function differences. We will examine the relations among sex hormones, pain
      processing, immune system substances and pain related genes. We will also examine changes in
      levels of hormonal and immune substances in the blood, endometriosis lesions and normal
      endometrial tissue. Myofascial pain has been noted in women with endometriosis and chronic
      pelvic pain. We will study how the nerve, muscle and skeletal systems are involved in pelvic
      pain by performing an in depth pain assessment. Finally, stress plays an important role
      generating and perpetuating chronic pain. We will examine how the hormones related to the
      stress response may be altered in pelvic pain.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        We plan to study women of reproductive age with chronic pelvic pain, some of whom have
        endometriosis and some who do not. Healthy women without chronic pelvic pain and not known
        to have endometriosis will serve as controls. In the event that endometriosis is found at
        laparoscopy in the control group, we will include these patients in the study as a separate
        subset of controls. Controls may choose to complete the study, including laparoscopy with a
        tubal ligation, complete the study without laparoscopy, or participate in an abbreviated
        study that includes only screening and chronic stress testing. All women will be protected
        from pregnancy by non-hormonal contraception such as barrier contraception, abstinence or
        surgical sterilization for the duration of the study.
      
Keywords: Myofascial Dysfunction; Sensitization; Healthy Volunteers; Overlapping Pain Conditions; Hypothalamic-Pituitary-Adrenal Axis; Natural History