Could not obtain approval for the planned study with available funding

The mechanisms underlying variable efficacy of Relugolix-Combination Therapy (REL-CT) in mitigating unexplained pelvic pain will be evaluated with uterine imaging techniques and quantitative sensory testing.

The mechanisms underlying variable efficacy of Relugolix-Combination Therapy (REL-CT) in mitigating unexplained pelvic pain will be evaluated with real-time uterine imaging techniques and quantitative sensory testing. Advanced MRI methodology enables the assessment of various uterine parameters, including contractions, peristalsis, perfusion, blood oxygenation, and structural factors. Importantly, it is possible to temporally correlate these mechanisms with self-reported spontaneous menstrual cramping pain through real-time imaging.

In the first aim of this proposal (Aim #1), mechanisms underlying unexplained menstrual pain phenotypes linked to deficiencies in myometrial activity, perfusion, and oxygenation and evaluate the subsequent impact of REL-CT will be evaluated. Aim #2 focuses on characterizing unexplained menstrual pain phenotypes associated with impairments in the central nervous system sensory functions and the effects of REL-CT. Quantitative sensory testing methods will be used to comprehensively assesses peripheral, central ascending, central integrating, and central descending nervous system components related to pelvic pain. In the past, this testing can identify central nervous system component pain that predicts the pain trajectory and corresponds with treatment outcomes.

By analyzing the relationship between the variable effectiveness of REL-CT treatment to observed mechanisms in menstrual pain, it may possible to identify specific unexplained pelvic pain phenotypes amenable to medical management. Furthermore, because that the precise mechanisms by which REL-CT alleviates menstrual pain in endometriosis remain incompletely understood, a cohort of endometriosis patients will be also studied. The overarching objective is to uncover the underlying mechanisms that advance the comprehension of menstrual pain biology and establish these mechanisms as phenotypic markers for treating REL-CT.

Inclusion Criteria

Idiopathic pelvic pain (40 participants):

• Self-report an average non-menstrual pelvic pain rating of ≥ 2/10 (on a 0 to 10 Numeric Rating Scale) over the past 6 months.
• Not have received a prior diagnosis attributed to a secondary cause (e.g., leiomyoma, endometriosis).

Endometriosis (20 participants)

• Self-report an average non-menstrual pelvic pain rating of ≥ 2/10 (on a 0 to 10 Numeric Rating Scale) over the past
• Previously confirmed surgical diagnosis of stage III-IV endometriosis, indicating potential remission.

Exclusion Criteria:

• History of blood clots,
• Allergies to REL-CT ingredients
• Diabetes
• Migraines
• Osteoporosis
• Vascular disease
• Hormone-sensitive cancers
• Smoking.
• Missing limbs
• Paralysis,
• Conditions associated with irregular menses
• Congenital conditions affecting reproductive function
• Intrauterine device use
• Pelvic inflammatory conditions
• Active genitourinary infections,
• Inability to read or comprehend the informed consent document written in English
• History of metallic implants, history of metallic injury, any condition precluding investigation with MRI
• BMI exceeding 40
• Uncontrolled thyroid dysfunction
• Adrenal dysfunction
• Renal disorders
• Liver disorders
• Coagulopathy,
• Gastrointestinal conditions or surgeries that may affect absorption

We plan to share anonymized data with potentially interested experience scientific researchers. Shared data includes pain diary, questionnaire data, MRI data, and sensory testing data.

18 months.

Data obtained through this study may be provided to qualified researchers with academic interest in pelvic pain. Data or samples shared will be coded, with no personally identifying included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.