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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Endometriosis, Chronic Pelvic Pain

Intervention / Treatment
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* Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy)
* Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br> | Drug: Continuous OC (clormadinone acetate plus ethinil-estradiol - Belara®, Grunenthal, Milan, Italy)<br>* 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.<br>|
| Active Comparator: Control<br> | Drug: Cyclic OC (clormadinone acetate plus ethinil-estradiol)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of pelvic pain |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |