Comparison of the effectiveness of valproic acid and dienogest in reducing endometriosis symptoms in patients with endometriosis

Providing scientific evidence for selecting more effective treatment in the management of endometriosis

A Phase 1-2, randomized, triple-blind, parallel-group, controlled clinical trial involving 120 patients. Random allocation will be performed using permuted blocks via the Random Allocation software.

This study is being conducted on patients with endometriosis presenting to the Mother and Child Hospital in Shiraz. Participants will be randomly assigned to two groups: Group A (receiving 2 mg Dienogest tablets) and Group B (receiving 500 mg Valproic acid tablets). Six months after the initiation of treatment, the reduction in endometriosis symptoms will be compared between the two groups. The study employs a triple-blind design; the patients, the researchers, and the outcome assessors remain blinded to the group assignments (Group A or Group B).

Inclusion Criteria • Women with a definitive diagnosis of endometriosis • No prior pharmacological treatment for endometriosis before the start of the study • No use of similar pharmacological treatments (dienogest or valproic acid) within the past three months • No known history of allergy or hypersensitivity to the medications Exclusion Criteria • Pregnancy or intention to become pregnant during the six-month treatment period • Presence of coagulation disorders or a history of thrombosis

Treatment group A will receive one 2 mg dienogest tablet daily (morning and evening) for 6 consecutive months. Treatment group B will receive two 500 mg valproic acid tablets daily (morning and evening) for 6 consecutive months.

The primary outcome is the severity of endometriosis-associated pelvic pain, which will be measured—prior to treatment, as well as 3 and 6 months after the initiation of treatment—using the Visual Analogue Scale (VAS).

Randomization will be performed using the "Random Allocation" software, employing a permuted-block randomization method. Specifically, various blocks of four (such as ABBA, BABA, ABAB, BBAA, AABB, and BABA) will be generated; one of these blocks will be randomly selected, and patients will be assigned to either Group A or Group B based on the sequence specified within the chosen block.

The study will be conducted as a triple-blind trial. In this study, patients will receive medications in packages coded as 'A' or 'B' and will remain unaware of the specific treatment they are receiving. The researcher will also be blinded to the treatment administered; they will provide the medication to patients in packages prepared by a collaborating pharmacist, with only the codes 'A' or 'B' marked on the packaging. Finally, the radiologist responsible for evaluating the findings from the patients' transvaginal ultrasound or pelvic MRI will also be unaware of the treatment the patients received.

Given that the Vice-Chancellery for Research at Shiraz University of Medical Sciences is the funding body for this research project, any dissemination of information or findings related to the project must be carried out with the consent of the Vice-Chancellery.