JMIR Publications

ABSTRACT

Background:

The treatment of endometriosis includes analgesics, hormone therapy, and surgery. Even after surgical removal of endometriotic lesions, the risk of recurrence remains high once the normal menstrual cycle resumes. Therefore, long-term hormone therapy is essential to prevent recurrence. Among hormonal treatments, low-dose estrogen progestin (LEP) preparations are not recommended for patients over 40 years of age due to the increased risk of thrombotic side effects. In contrast, dienogest (DNG) does not carry a thrombotic risk, making it a suitable option for older patients. Although DNG requires long-term administration until menopause in patients with endometriosis, data on its long-term efficacy and potential adverse effects remain limited. In particular, comparative studies assessing the safety and effectiveness of long-term use of DNG at different doses (1 mg/day vs. 2 mg/day) have not been conducted, highlighting the need for further investigation.

Objective:

This manuscript presents the study protocol and does not include any preliminary data. The purpose of this study is to investigate the efficacy and the incidence of adverse events of DNG 1 mg/day after 48 weeks in patients with dysmenorrhea due to endometriosis, compared with DNG 2 mg/day.

Methods:

This randomized, open-label, parallel-group, dose-comparison, multicenter trial follows the SPIRIT 2013 guidelines and is conducted at six centers in Japan. Subjects are randomly assigned in a 1:1 ratio to the DNG 1 mg/day and 2 mg/day groups. The drug is administered for 48 weeks, and therapeutic effects and side effects are investigated. Hospital visits include questionnaires, vital signs measurements, and imaging (Magnetic Resonance Imaging and ultrasound: MRI, ultrasound), blood tests, and bone density assessments. The primary endpoint is the change in the pain Visual Analogue Scale (VAS)from baseline to 48 weeks. The VAS is a 10 cm horizontal scale used to measure pain intensity, where 0 cm represents no pain and 10 cm represents the maximum imaginable pain. Participants will mark their pain level on the scale, and the change in scores over the study period will be analyzed. The target number of cases is 88, set with a non-inferiority margin based on existing reports. The protocol was approved by the Nagoya City University Hospital Clinical Research Review Board. Data will be presented at academic conferences and published in peer-reviewed journals.

Results:

Currently, data collection is ongoing. The first participant was enrolled in August 2021. As of March 22, 2025, a total of 88 participants had been enrolled in this clinical trial.

Conclusions:

This is the first trial to compare efficacy and safety between 1 mg/day and 2 mg/day of long-term DNG use in patients with dysmenorrhea caused by endometriosis. Combining diagnostic imaging with patient questionnaires and blood tests allows determination of efficacy against endometriosis itself. Clinical Trial: jRCTs041210016 (Japan Registry of Clinical Trials)