Continuous Postoperative Use of Low-Dose Combined Oral Contraceptivesfor for Endometriosis-Related Chronic Pelvic Pain

Continuous Versus Cyclic Postoperative Use of Low-Dose Combined Oral Contraceptive Belara® for the Treatment of Endometriosis-Related Chronic Pelvic Pain: a Randomized Controlled Trial.

Because ovarian sex steroids fluctuations during the menstrual cycle are implicated in the pathogenesis of the endometriosis-related chronic pelvic pain (CPP), the oral contraceptives (OCs) are used with non-contraceptive indication for this disorder.

To date, OCs are widely used as medical treatment in patients with endometriosis, in addition, they are recently experimented as post-surgical therapy. Traditional cyclic regimen, with 21 days of active pills with 7 days of placebo or suspension, is usually adopted. Furthermore, recent studies suggested that long-term continuous OCs use can be effective in the postoperative period both as second- and third- line treatments after cyclic regimen failure. In these studies a combined treatment with ethinilestradiol (0.02 mg) plus desogestrel (0.15 mg) were used and compared with baseline or ciproterone acetate.

A recent study showed a deeper ovarian and endometrial suppression with continuous OCs in comparison with cyclic OCs, providing a physiological rationale for continuous OCs use for noncontraceptive indications. Furthermore, to date, no study compared post-operative continuous versus cyclic OCs in patients with endometriosis-related CPP.

Study Overview

• Status: Unknown
• Conditions: Endometriosis; Chronic Pelvic Pain
• Intervention / Treatment: Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy); Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol)

Detailed Description

Premenopausal women with endometriosis-related CPP scheduled for laparoscopic surgery to our Academic Department of Gynecology will be consecutively enrolled. Subjects with hystologically confirmed endometriosis at laparoscopy (stage I-IV of the American Society Reproductive Medicine), a subjective severity of pelvic pain by using a visual analogue scale (VAS 1-100) of at least 70, and without immediate desire of pregnancy will be enrolled.

Briefly, all patients will undergo conservative laparoscopic surgery for endometriosis. Thereafter, a low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered. Patients from the experimental group will be treated with a continuous regimen, while patients from the control group will receive the OC with a cyclic regimen consisting of 21 days of active pills with 7 days of placebo. The drug and the placebo will be similar and will be labelled according to the subject number. For the overall study-period, operators and patients will be blind to the treatment allocation.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • University of Catanzaro, Italy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Premenopausal state
• Endometriosis-related chronic pelvic pain
• Hystologically confirmed endometriosis at laparoscopy
• Subjective severity of pelvic pain by using a visual analogue scale of at least 70
• No immediate desire of pregnancy

Exclusion Criteria:

• Age ≤18 or ≥ 40
• Previous use of drugs for treating CPP (wash-out period of 3 months), with exclusion of non-steroidal anti-inflammatory drugs
• Contraindication to estro-progestin compounds
• Major medical diseases
• Psychiatric disorders
• Pelvic inflammatory disease
• Adnexal patologies
• Unability to complete the daily diary
• History of alcohol or other drugs abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy); Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a continuous regimen.
Active Comparator: Control	Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol); Low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered with a cyclic regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence of pelvic pain	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	12 months
Quality of life	12 months
Metabolic effects	12 months
Ovarian effects	12 months
Endometrial effects	12 months
Bleedings characteristics	12 months
Protocol adherence	12 months
Satisfaction rate	12 months
Effects on cognitive function and mood	12 months

Collaborators and Investigators

• Sponsor: University Magna Graecia

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Anticipated): May 1, 2010
• Study Completion (Anticipated): July 1, 2010

Study Registration Dates

• First Submitted: February 12, 2009
• First Submitted That Met QC Criteria: February 12, 2009
• First Posted (Estimate): February 13, 2009

Study Record Updates

• Last Update Posted (Estimate): March 12, 2009
• Last Update Submitted That Met QC Criteria: March 10, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Endometriosis; Pelvic Pain; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 01/2009