Medical Treatment of Endometriosis-Associated Pelvic Pain

Oral Contraceptives Versus Depot-Leuprolide Taken After Surgery for Endometriosis-Associated Pelvic Pain

The Specific Aim of this project is to compare the efficacy and cost-effectiveness of continuous oral contraceptives versus leuprolide/norethindrone in the treatment of endometriosis-associated chronic pelvic pain. This comparison will be based on a randomized, double-blind, trial of women with chronic pelvic pain who have been diagnosed with endometriosis at the time of surgery within the last 3 years. We hypothesize that, over a 12-month period of postoperative treatment, the efficacy of oral contraceptives is no worse than leuprolide/norethindrone, and that treatment with oral contraceptives is more cost-effective.

Study Overview

• Status: Completed
• Conditions: Endometriosis; Pelvic Pain
• Intervention / Treatment: Drug: Oral Contraceptive; Drug: Depot-Leuprolide/Norethindrone

Detailed Description

• Background-Laparoscopic surgical treatment for endometriosis is typically associated with a decrease of pain on a short-term basis, but 50% of patients have pain 12 months after surgery. Often this leads to having repeat surgery to treat the endometriosis. Instead of having repeat surgery, some physicians use medications to prevent the pain and endometriosis from returning.
• The purpose of this study is to compare continuous oral contraceptives to depot-leuprolide for control of endometriosis-associated pelvic pain after surgical treatment of endometriosis. We will also be looking at the potential cost savings of using oral contraceptives compared to depot-leuprolide, as depot-leuprolide is an expensive medication.
• If the patient meets criteria, including confirmation of diagnosis of endometriosis, she will then undergo an intake visit consisting of obtaining informed consent and completion of several baseline questionnaires. This intake visit is estimated to last 1-2 hours. After informed consent has been obtained, the subject will be randomized to one of the two treatment groups:One tablet of oral contraceptives (birth control pills) everyday and an injection of saline (a sterile salt solution with no medication effect) every 12 weeks for 48 weeks or One tablet of norethindrone everyday and an injection of depot-leuprolide every 12 weeks for 48 weeks.
• The patient will be seen one month after the first injection (Visit 1) and then at 12 (Visit 2), 24 (Visit 3), 36 (Visit 4) and 48 (Visit 5) weeks. Blood pressure and weight will be recorded and a urine pregnancy test will be obtained. The Study Coordinator will review with the patient any concerns she might have and record any adverse events. Assessments of pain and quality of life will be made at weeks 4, 12, 24, 36 and 48 after the intake visit. An injection (leuprolide acetate or saline plus inert powder) will be given by an unblinded nurse at the intake visit, and at weeks 12, 24, and 36. In addition, at the end of each medication visit, the patient will be given a three month's supply of oral medication (capsules containing norethindrone acetate or a generic oral contraceptive with 30ug ethinyl estradiol and 0.15mg levonorgestrel).

• Study Type: Interventional
• Enrollment (Anticipated): 194
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Brigham and Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 52 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age greater than 18 and pre-menopausal.
• Pelvic pain of at least 3 months duration.
• Diagnosis of endometriosis by laparoscopy or laparotomy within three years of entry. The diagnosis of endometriosis will require either histology consistent with endometriosis or operative records indicating visual evidence of lesions consistent with endometriosis.
• Moderate to severe pelvic pain preoperatively attributable to endometriosis (average Numerical Rating Scale of 5 or more for three or more months).
• Willingness to comply with visit schedule and protocol.

Exclusion Criteria:

• Use of oral contraceptives within one month of the surgery.
• Dose of Lupron within three months if given monthly or within five months if given 3-month injection.
• Any disorder that represents a contraindication to the use of oral contraceptives (e.g. insulin-dependent diabetes mellitus, history of thrombophlebitis, hypertension, history of cardiovascular disease, smoker at 35 or more years of age) or GnRH analogs (e.g., history of osteopenia).
• History of hysterectomy and bilateral salpingoophorectomy.
• Positive pregnancy test at first postoperative (i.e, intake visit).
• Significant mental or chronic systemic illness that might confound pain assessment or the inability to complete the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
quality of life
pain

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: David S Guzick, M.D., Ph.D, University of Rochester; Principal Investigator: Mark Hornstein, MD, Brigham and Women's Hospital; Principal Investigator: Fred M Howard, MD, University of Rochester; Principal Investigator: Sara Sukalich, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start: July 1, 2004

Study Registration Dates

• First Submitted: September 28, 2005
• First Submitted That Met QC Criteria: September 28, 2005
• First Posted (Estimate): September 30, 2005

Study Record Updates

• Last Update Posted (Estimate): January 24, 2014
• Last Update Submitted That Met QC Criteria: January 23, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: treatment; endometriosis; pelvic pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Endometriosis; Pelvic Pain; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Leuprolide; Contraceptive Agents; Contraceptives, Oral; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: R01HD044870 (U.S. NIH Grant/Contract)