Mechanistic Characterization of Uterine Pain

Description

There are limited treatment options for management of dysmenorrhea, and the physiological processes they affect are not completely understood. For example, NSAIDs are effective in reducing menstrual pain in some women by inhibition of prostaglandin synthesis, but whether those effects are mediated by affecting contractility, perfusion, or hypoxemia is unknown. Understanding how these drugs relieve menstrual pain (and why they fail) would be of substantial clinical significance. Given the foregoing, Two Specific Aims are proposed: Aim #1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI scans of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. The investigators will include cohorts of women with imaging diagnosed leiomyoma and surgically-confirmed endometriosis to evaluate the contribution of structurally identifiable factors. Based on preliminary data, the investigators anticipate finding four phenotypes with menstrual pain related to: 1) myometrial activity, 2) inadequate perfusion and/or oxygenation, 3) a combination of phenotypes 1 \& 2, and 4) a non-uterine source. Aim #2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. In women with primary dysmenorrhea, the investigators will acquire pelvic MRI scans and evaluate self-reported menstrual cramping pain before and after administration of randomized naproxen or placebo. Naproxen could principally affect one or more potential sources of uterine pain such as myometrial activity, perfusion, and/or oxygenation. The investigators will corroborate preliminary data findings, which suggest menstrual phenotypes with myometrial activity will be more likely to respond. Conversely, Aim 2 will also elucidate the mechanisms responsible for inadequate pain relief from naproxen. Bioavailability of naproxen levels and other molecules associated with NSAID-resistance will be evaluated from the serum of participants after taking naproxen using HPLC-MS.

Conditions

Dysmenorrhea (Disorder), Dysmenorrhea Primary, Dysmenorrhea Secondary, Endometrial Diseases, Leiomyoma, Fibroid Uterus

Study Overview

Study Details

Study overview

There are limited treatment options for management of dysmenorrhea, and the physiological processes they affect are not completely understood. For example, NSAIDs are effective in reducing menstrual pain in some women by inhibition of prostaglandin synthesis, but whether those effects are mediated by affecting contractility, perfusion, or hypoxemia is unknown. Understanding how these drugs relieve menstrual pain (and why they fail) would be of substantial clinical significance. Given the foregoing, Two Specific Aims are proposed: Aim #1: Characterize menstrual pain phenotypes associated with impairments in myometrial activity, perfusion, and/or oxygenation. Continuous MRI scans of the uterus will be performed with simultaneous measurement of self-reported pain in healthy women and those experiencing menstrual pain. The investigators will include cohorts of women with imaging diagnosed leiomyoma and surgically-confirmed endometriosis to evaluate the contribution of structurally identifiable factors. Based on preliminary data, the investigators anticipate finding four phenotypes with menstrual pain related to: 1) myometrial activity, 2) inadequate perfusion and/or oxygenation, 3) a combination of phenotypes 1 \& 2, and 4) a non-uterine source. Aim #2: Evaluate the effects of naproxen on myometrial activity, perfusion, and/or oxygenation with respect to pain relief. In women with primary dysmenorrhea, the investigators will acquire pelvic MRI scans and evaluate self-reported menstrual cramping pain before and after administration of randomized naproxen or placebo. Naproxen could principally affect one or more potential sources of uterine pain such as myometrial activity, perfusion, and/or oxygenation. The investigators will corroborate preliminary data findings, which suggest menstrual phenotypes with myometrial activity will be more likely to respond. Conversely, Aim 2 will also elucidate the mechanisms responsible for inadequate pain relief from naproxen. Bioavailability of naproxen levels and other molecules associated with NSAID-resistance will be evaluated from the serum of participants after taking naproxen using HPLC-MS.

Mechanistic Characterization of Uterine Pain (MCUP) to Improve Diagnosis and Treatment for Dysmenorrhea

Mechanistic Characterization of Uterine Pain

Condition
Dysmenorrhea (Disorder)
Intervention / Treatment

-

Contacts and Locations

Evanston

NorthShore University HealthSystem, Evanston, Illinois, United States, 60201

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. 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.
  • 2. inability to read or comprehend the informed consent written in English,
  • 3. history of metallic implants,
  • 4. history of metallic injury,
  • 5. any diagnosed condition that would preclude investigation with MRI (e.g., claustrophobia),
  • 6. BMI \>40,
  • 7. allergy or inability to tolerate naproxen
  • 1. thyroid dysfunction,
  • 2. adrenal dysfunction,
  • 3. renal disorders,
  • 4. liver disorders,
  • 5. coagulopathy,
  • 6. prolactinoma,
  • 7. von Willebrand disease,
  • 8. platelet disorders,
  • 9. diabetic neuropathy,
  • 10. gastrointestinal conditions or surgeries that would affect naproxen absorption,
  • 11. active genitourinary or sexually transmitted infection

Ages Eligible for Study

18 Years to 45 Years

Sexes Eligible for Study

FEMALE

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

NorthShore University HealthSystem,

Kevin M Hellman, PhD, PRINCIPAL_INVESTIGATOR, NorthShore University HealthSystem

Study Record Dates

2024-09-01