The goal of this clinical trial is to learn if NSAIDs (i.e. naproxen sodium) can treat menstrual pain and prevent the development of chronic pelvic pain in menstruating adults with painful periods. The main questions it aims to answer are:

• Can non-menstrual pelvic pain reduction be predicted by menstrual pain response to NSAIDs?
• Will participants with the largest reductions in multi-site sensitivity following NSAID therapy have the largest reductions in non-menstrual pelvic pain?

Researchers will compare naproxen sodium to a placebo (a look-alike substance that contains no drug) to see if naproxen sodium works to treat painful periods.

Participants will:

• Take naproxen sodium or placebo during several days of their menstrual period every month for 1 year.
• Complete computer questionnaires and tests from home every 3 months.
• Complete at-home urine tests to measure hormones every few days for 1-year.
• Use a pin-prick to collect a small spot of blood, and use a pad or tampon to collect a sample of menstrual blood, and bring it to the research site twice over a 1-year period.
• Come to the research site twice over a 1-year period to complete sensory assessments and undergo a blood draw.

The major goal of the study is to develop a multivariable statistical model (see https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-24-021.html ) describing the factors that effectiveness of pain medication and risk for chronic pain

Inclusion Criteria:

• aged 18-35
• individuals who menstruate, with painful periods
• regular menstrual cycles (every 22-35 days)

Exclusion Criteria:

• presence of active pelvic or abdominal malignancies (primary or metastatic)
• conditions associated with the absence of regular menses such as polycystic ovarian syndrome, pregnancy, or any current use of continuous hormonal medication or contraceptive
• unable to read or comprehend the informed consent in English
• presence of other diagnosed chronic back or pelvic pain conditions (including chronic back pain, fibromyalgia, bladder pain syndrome, irritable bowel syndrome, vulvar pain syndrome, and endometriosis-associated pelvic pain)
• having another diagnosed/symptomatic chronic pain condition besides migraines with an average pain score >3/10 in the last month when not consuming pain relievers, or that requires daily treatment with opioids (ex. hydrocodone, oxycodone, codeine, morphine, hydromorphone, tapentadol, tramadol) or neuromodulators (also known sometimes as antidepressants [ex. amitriptyline, nortriptyline, imipramine, duloxetine, milnacipran, venlafaxine] or antiseizure medications [ex. topiramate, gabapentin, pregabalin, carbamazepine, lamotrigine])
• current or past history of stomach ulcers
• current or past history of gastrointestinal (GI) bleeding
• diagnosis of peptic ulcer disease
• current or past history of renal disorders
• current or past history of adrenal dysfunction
• diagnosis of liver disorders
• diagnosis of chronic acid reflex (i.e. GERD)
• Diagnosis of Crohn's disease or ulcerative colitis
• Coagulopathy
• Prolactinoma
• Von Willebrand disease
• Platelet disorders
• High blood pressure that is difficult to manage
• gastrointestinal conditions or surgeries that affect naproxen absorption
• bleeding disorders
• heart failure
• a history of stroke
• a history of heart attack
• active genitourinary or sexually transmitted infection
• allergy to non-steroidal anti-inflammatory drugs (NSAIDs) or their ingredients
• individuals who take the following medications: anticoagulants (i.e. warfarin), lithium, diuretics, antacids, angiotensin-converting enzyme (ACE) inhibitors, methotrexate, cholestyramine, or probenecids.
• Unmanaged diabetes (i.e. Fasting Blood Glucose: ≥ 126 mg/dL (≥ 7.0 mmol/L), Non-Fasting/Random Blood Glucose: ≥ 200 mg/dL (≥ 11.1 mmol/L), Hemoglobin A1c (HbA1c): ≥ 6.5%)
• Uncontrolled thyroid function (i.e. Hypothyroidism (Underactive Thyroid): Thyroid-Stimulating Hormone (TSH): > 4.5 mIU/L (mild) or > 10 mIU/L (severe) Free T4: Below the lower end of the reference range (usually < 0.9 ng/dL)
• Hyperthyroidism (overactive thyroid) (i.e. TSH: < 0.4 mIU/L (Suppressed or undetectable), Free T4: Above the upper end of the reference range (usually > 2.0 ng/dL)
• Liver dysfunction (i.e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or bilirubin (unless known diagnosis of Gilbert's syndrome) ≥ 1.5 times the upper limit of the reference range)
• Kidney dysfunction (i.e. Serum creatinine > 1.1 mg/dL.)

The investigators will share these HEAL common Data Elements (CDEs): 1. Pain Intensity (PEG), 2. PROMIS Pain Interference, 3. PROMIS Physical functioning/quality of life, 4. PROMIS Sleep, 5. Pain catastrophizing (Sullivan 1995), 6. PROMIS Depression, 7. PROMIS Anxiety, 8. Global Satisfaction with Treatment (PGIC), 9. Substance Abuse (TAPS 1). The investigators will also share these HEAL-recommended demographics: age, sex at birth, gender identity, ethnicity, race, highest level of education, employment status, relationship status, annual household income, applied for disability insurance, pain duration, and postal code. The investigators will also share several data elements that lack a unified standard.

Electronic copies of our research publications will be deposited in PubMed Central within four weeks of acceptance by a journal, complete with appropriate metadata to ensure discoverability and accessibility upon publication. All publications will be released under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent open-access license. There will be no embargo period for the public availability of our publications. The underlying primary data supporting our publications will be made widely accessible through DASH, a HEAL-compliant repository. To the extent feasible, The investigators aim to share the underlying primary data concurrently with the publication, ensuring immediate access. All primary data shared will be subject to the CC BY 4.0 license or an equivalent open-access license.

The IPD will be widely accessible via DASH, a Heal-compliant registry.