Letrozole in Preventing Recurrence of Endometrioma Following Laparoscopic Ovarian Cystectomy

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.

Study Overview

• Status: Recruiting
• Conditions: Endometriotic Cyst of Ovary
• Intervention / Treatment: Other: Placebo; Drug: Letrozole

• Study Type: Interventional
• Enrollment (Anticipated): 194
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Pamela Youde Nethersole Eastern Hospital
    • Contact: Catherine K.Y. Wong
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Princess Margaret Hospital
    • Contact: Rebecca S.F. Wan, MBBS, MRCOG
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Queen Elizabeth Hospital
    • Contact: Keedon Wong
  • Hong Kong, Hong Kong, 000000
    • Recruiting
    • Queen Mary Hospital
    • Contact: Jennifer K.Y. Ko, MBBS, MRCOG; Phone Number: 22554647; Email: jenko@hku.hk
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Kwong Wah Hospital
    • Contact: Mei Ting Lam, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole; 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; Letrozole 2.5mg daily for 6 months
Placebo Comparator: Standard treatment; 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; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Princess Margaret Hospital, Canada; Kwong Wah Hospital; Pamela Youde Nethersole Eastern Hospital; The Queen Elizabeth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): June 30, 2027

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: recurrence; letrozole; combined oral contraceptive pills; endometriotic cyst
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Endometriosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: UW21-556

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No