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

Phase 4

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

• Registration Number: NCT00844012
• Lead Sponsor: University Magna Graecia

Brief Summary

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.

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 Timeline

• Status Verified: 2009-02
• Study First Submitted: 2009-02-12
• Study First Submitted QC: 2009-02-12
• Study First Posted: 2009-02-13
• Last Update Submitted: 2009-03-10
• Last Update Posted: 2009-03-12
• Study Start: 2009-05
• Primary Completion: 2010-05
• Study Completion: 2010-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Cyclic OC (clormadinone acetate plus ethinil-estradiol)	-
Experimental group	Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy)	-

Primary Outcome Measures

Name	Time	Method
Recurrence of pelvic pain	12 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Catanzaro, Italy; 🇮🇹 Catanzaro, Italy