Letrozole in Preventing Recurrence of Endometrioma Following Laparoscopic Ovarian Cystectomy

Study Overview
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Brief Summary
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Endometriosis is a chronic inflammatory disease that affects approximately 10-15% of women of reproductive age. Symptoms include dysmenorrhoea, chronic pelvic pain, dyspareunia and infertility. Removal of the endometriotic cyst (chocolate cyst) by surgery is a well-established treatment for symptomatic relief. However, recurrence of endometriotic cyst after surgical removal of the cyst is up to 30-50% after ovarian surgery. Oral contraceptive pills for 18-24 months after the surgery is widely used as a postoperative hormonal therapy because it has been shown to reduce the chance of recurrence of the endometriotic cyst, but recurrence is still high even after taking oral contraceptive pills. Letrozole is an aromatase inhibitor. There are some preliminary reports that letrozole can cause shrinkage of endometriotic cysts and improve endometriosis-related pelvic pain by reducing oestrogen level, inflammation and stem cell recruitment that may be important in recurrence of endometriotic cyst. This is a randomized double-blinded placebo-controlled trial. The aim of this study is to assess whether taking letrozole in addition to oral contraceptive pills in the first 6 months after laparoscopic surgery (key-hole surgery) to remove the endometriotic cyst can reduce the risk of recurrence compared to oral contraceptive pills alone. The study also involves laboratory parts from a small portion of the endometriotic cyst specimens (removed during laparoscopy ovarian cystectomy) and endometrial biopsy (if the patient agrees) to assess the role of stem cells in the pathogenesis of endometriotic cysts.

Official Title
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Letrozole in Preventing Recurrence of Endometrioma Following Laparoscopic Ovarian Cystectomy

Conditions
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Endometriotic Cyst of Ovary

Intervention / Treatment
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* Drug: Letrozole
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18-45 years old Scheduled to have laparoscopic ovarian cystectomy Unilateral or bilateral endometrioma on pre-operative ultrasound and confirmed by histology Exclusion Criteria: Use of long-acting hormonal therapy in the 3 months before inclusion in the study Histological report of laparoscopic ovarian cystectomy showed atypical endometrioma Complex surgery including resection of deep infiltrating disease, bowel resection or hysterectomy Incomplete excision of endometrioma/ incision or drainage rather than ovarian cystectomy Suspicion of malignancy Contraindications to combined oral contraceptive pills, including: uncontrolled hypertension (systolic > 160mmHg or diastolic > 100mmHg), diabetes with retinopathy/ nephropathy/ neuropathy, current or past history of venous thromboembolism, ischemic heart disease, history of cerebrovascular accident, migraine with aura, severe liver disease, oestrogen-sensitive cancers, undiagnosed abnormal uterine bleeding, smokers (> 15 cigarettes/day) aged 35 years or above, or having body mass index >=35 kg/m2 Planning to get pregnant in the coming 1 year Refusal to join the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br>They will be given letrozole 2.5mg daily on top of combined oral contraceptive (COC) pills (Microgynon 30, which contains 30mcg ethinyloestradiol and 150 mcg levonorgestrel) orally for 6 months after laparoscopic ovarian cystectomy, followed by COC pills alone subsequently as routine | Drug: Letrozole<br>* Letrozole 2.5mg daily for 6 months<br>|
| Placebo Comparator: Standard treatment<br>They will be given placebo tablets (which will be identical to letrozole) on top of COC pills (Microgynon 30, which contains 30mcg ethinyloestradiol and 150 mcg levonorgestrel) orally for 6 months after laparoscopic ovarian cystectomy, followed by COC pills alone subsequently | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of endometrioma | the presence of ovarian cysts with the typical sonographic criteria of endometriomas and a diameter of ≥30 mm after previous complete ovarian cystectomy, to be measured by a transvaginal or transrectal ultrasound transducer | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometriosis Health Profile Questionnaire (EHP-30) score | a validated disease-specific health related quality of life patient self-reported scale for endometriosis used to measure the effects that endometriosis can have on the women's lives and the effectiveness of medical and surgical therapies for endometriosis on their quality of life | 6 months, 12 months, 24 months | 
| Non-menstrual pelvic pain (chronic pelvic pain, deep dyspareunia) and dysmenorrhoea measured by a 10cm visual analogue pain scale (VAS) | 0-100 | 6 months, 12 months, 24 months | 
| Menstrual regularity | menstrual chart | 6 months, 12 months, 24 months | 
| Use of additional analgesics |  | 6 months, 12 months, 24 months | 
| Side effects/ adverse events | Number of women with side effects/ adverse events | 6 months, 12 months, 24 months | 
| Need for further surgery for endometriosis | Number of women who required further surgery for endometriosis | 6 months, 12 months, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrence, endometriotic cyst, letrozole, combined oral contraceptive pills