Feasibility of Body Identical Progesterone for treatment of endometriosis pain (BIP-4)

Background Endometriosis affects 10–15% of women* of reproductive age and is associated with chronic pelvic pain, fatigue, and reduced quality of life. Current first-line medical treatments, such as synthetic progestins (e.g., Dienogest), are often discontinued due to side effects, with up to 20% unable to tolerate them. Reports and patient advocacy groups have called for safer, more effective oral treatment options. Micronised progesterone (MP), a body-identical hormone, may offer a better-tolerated alternative to synthetic progestins. Preclinical evidence suggests MP could reduce ectopic endometrial tissue proliferation while offering a favourable side-effect profile, including mood stabilisation—particularly when administered vaginally. Despite growing interest, MP is not licensed or routinely offered for endometriosis treatment in the NHS. Research Question Is it feasible to conduct a full-scale randomised controlled trial (RCT) evaluating oral or vaginal MP versus synthetic progestin (Dienogest) for endometriosis? Aim and Objectives Assess recruitment, retention, and adherence to inform a full RCT comparing MP and Dienogest. Evaluate acceptability and preference for oral/vaginal MP versus Dienogest to determine the preferred route for a future trial. Identify challenges and enablers for NHS implementation. Methods We will conduct a three-arm open-label feasibility RCT in two specialist endometriosis clinics (Royal London and Whipps Cross Hospitals, Barts Health NHS Trust). Population: 75 women (age 18–52) with imaging/laparoscopy-confirmed endometriosis, no prior Dienogest use, and willing to use barrier contraception for 6 months. Intervention: Participants will be randomised (1:1:1) to receive: MP 300 mg oral tablets MP 300 mg vaginal pessaries Dienogest 2 mg oral tablets Outcomes: Primary—process outcomes including recruitment, retention, adherence, and treatment acceptability (participants and clinicians). Secondary—pain (NRS), dysmenorrhea, dyspareunia, chronic pelvic pain, most bothersome symptom (MYMOP), mental health (HADS), side effects (TSQM-II), quality of life (EQ-5D-5L, Brief Pain Inventory), and healthcare resource use. Process Evaluation: Semi-structured interviews with participants from all arms (including non-completers) and healthcare professionals will explore barriers, facilitators, and the impact of MP on daily life. A qualitative descriptive approach will be used. Two workshops (patients and clinicians) will review findings to inform the design of a future EME application and determine the optimal MP delivery route. Timeline Months 1–7: Ethics approvals, site setup, staff recruitment. Months 8–13: Participant recruitment and data collection. Months 14–20: Follow-up. Months 21–22: Data cleaning and qualitative interviews. Months 23–25: Analysis, interpretation, and stakeholder input. Months 25–26: Reporting, publication, and dissemination. Impact and Dissemination Findings will inform a future NIHR EME application for a full-scale multi-centre RCT evaluating the clinical and cost-effectiveness of MP. Results will be disseminated through peer-reviewed publications, conferences, and accessible materials via email and social media. *For the purposes of this study, we use the term ‘women’ to refer to participants who experience endometriosis, including those who may not identify as women.