Mechanistic Characterization of Uterine Pain

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• active genitourinary or sexually transmitted infection; Provisional exclusion for primary analyses for all study participants: Acute or chronic conditions associated with pelvic pain with a defined anatomical cause other than endometriosis or leiomyoma (e.g., pathological ovarian cysts, significant persistent hydro/hematosalpinx, untreated pelvic inflammatory disease, active pelvic or abdominal malignancies, Mullerian anomalies, or stage 3 uterine prolapse), and comorbid diagnosis of significant leiomyoma and endometriosis; Note: these exclusion criteria may be incidentally discovered after the MRI scan and confirmed with a radiologist's or Dr. Tu's diagnosis; Provisional exclusion for adenomyosis group: Because the frequency of adenomyosis is low or unknown, and may consist of multiple subtypes resulting in heterogeneity and inadequate statistical power, adenomyosis patients are not a planned study group and diagnosed cases will be initially excluded from recruitment. Focal and diffuse adenomyosis will be excluded by guidelines (Chapron et al., 2017) adapted from the Kishi criteria (Kishi et al., 2012): maximal junctional zone thickness exceeding 12 mm, a ratio of junctional zone thickness to myometrium exceeding 40%, or high-intensity foci within the myometrium. If a substantial number of adenomyosis participants participate, as discovered after-the-fact with MRI, results will be analyzed; Intermediate levels of dysmenorrhea pain exclusion: Participants with mild menstrual pain (between 3 and 5 on a 0-10 scale) will be excluded. Our prior experience with this cohort (Westling et al., 2013) suggests that The investigators may encounter a floor effect when studying the effectiveness of NSAIDs. Also, since this cohort is most likely to respond to NSAIDs, it is imperative The investigators study the mechanisms of the most severe sufferers of refractory menstrual pain
• Menstruation-related exclusion criteria for all study participants: The investigators will exclude certain participants with conditions associated with the absence of regular menses such as polycystic ovarian syndrome, pregnancy, current use of any continuous hormonal medication or contraceptive, or Asherman's syndrome
• history of metallic implants,
• history of metallic injury,
• any diagnosed condition that would preclude investigation with MRI (e.g., claustrophobia),
• allergy or inability to tolerate naproxen
• renal disorders,
• liver disorders,
• von Willebrand disease,
• gastrointestinal conditions or surgeries that would affect naproxen absorption,
• platelet disorders,
• Age restrictions for all study participants: Regularly menstruating women (age 18-45) will be identified using our well-tested community-wide recruitment strategy, including approaching our division's busy gynecological disorders clinic, and the departments of Ob/Gyn at NorthShore and the University of Chicago. Although women above the age of 45 can have menstrual pain, irregularities in perimenopause could cause confounding effects on uterine physiology and scheduling difficulty. Similarly, irregularities in menstruation, ovulation, and pain levels in participants under age 18 could potentially detract from meaningful interpretation of phenotypes (Seidman et al., 2018). Additionally, before age 18, the uterus is still developing and substantially increasing in size (Porcu et al., 1989; Verguts et al., 2013). Thus, to limit potential confounding effects, participants under the age of 18 will be investigated in a separate study
• MRI-related or participation related exclusion criteria for all study participants:
• The investigators will exclude participants with criteria that would affect our ability to obtaining meaningful MRI data such as
• presence of an intrauterine device (IUD). The use of an IUD potentially affects interpretability of MRI because it creates an imaging artifact in the endometrium extending to the myometrium
• inability to read or comprehend the informed consent written in English,
• BMI >40,
• thyroid dysfunction,
• adrenal dysfunction,
• coagulopathy,
• prolactinoma,
• diabetic neuropathy,