Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring in Treatment of Women With Primary Dysmenorrhea (MK-8342B-060)

Inclusion Criteria:

- Post-menarcheal female, age ≤50 years, in good physical and mental health.

- History of moderate to severe primary dysmenorrhea for the past 3 months or longer,
and no history of recurrent non-menstrual pelvic pain intermittently or continuously
throughout the month, and no history of dysmenorrhea secondary to structural pelvic
pathology.

- Body mass index (BMI) of ≥18 and <38 kg/m^2.

- History of regular menstrual cycles with a cycle length between 24 and 32 days
(inclusive) for the past three months.

- Willing to adhere to use of the vaginal ring and to all required trial procedures,
and not planning to relocate during the study.

- Willing to use the rescue medication ibuprofen at the study recommended dose and no
other pain medication for treatment of dysmenorrhea.

Exclusion Criteria:

- Cardiovascular risks and disorders, including history of venous thromboembolic [VTE]
events, arterial thrombotic or thromboembolic [ATE] events, transient ischemic
attack, angina pectoris, or claudication; at higher risk of VTE events due to recent
prolonged immobilization, plans for surgery requiring prolonged immobilization, or a
hereditary or acquired predisposition or elevated risk for venous or arterial
thrombosis; currently smoking or uses tobacco/nicotine containing products and is ≥35
years of age; uncontrolled or severe hypertension; history of severe
dyslipoproteinemia; <35 years of age with a history of migraine with aura or focal
neurological symptoms or ≥35 years of age with a history of migraines with or without
aura or focal neurologic symptoms; diabetes mellitus with end-organ involvement or
>20 years duration; multiple cardiovascular risk factors such as ≥35 years of age,
obesity, inadequately controlled hypertension, use of tobacco/ nicotine products, or
inadequately controlled diabetes.

- Gynecologic conditions: surgically sterilized, has used hormonal contraceptives
(pill, patch, ring, implant, intrauterine system) within the past 3 months, or
currently uses non-hormonal intrauterine device (IUD); within past 6 months has had
undiagnosed (unexplained) abnormal vaginal bleeding or any abnormal vaginal bleeding
expected to recur during study; has gonorrhea, chlamydia, or trichomonas or
symptomatic vaginitis/cervicitis; has abnormal cervical smear or positive high-risk
human papillomavirus (HPV) test at screening or documented within 3 years of
screening; has Stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser
degrees of prolapse with history of difficulty retaining tampons, vaginal rings, or
other products within vagina.

- Gastrointestinal and urologic disorders, including history of pancreatitis associated
with severe hypertriglyceridemia; clinically significant liver disease, including
active viral hepatitis or cirrhosis; or a history of the gastrointestinal or urologic
tract which may cause pelvic pain.

- Other medical disorders, including history of malignancy ≤5 years prior to signing
informed consent except for adequately treated basal cell or squamous cell skin
cancer or in situ cervical cancer; any disease that may worsen under hormonal
treatment such as disturbances in bile flow, systemic lupus erythematosus, pemphigoid
gestationis or idiopathic icterus during previous pregnancy, middle-ear deafness,
Sydenham chorea, or porphyria; known allergy/sensitivity or contraindication to the
investigational products or their excipients; known allergy/sensitivity or
contraindication to ibuprofen, or has experienced asthma, urticaria, or allergic-type
reactions after taking aspirin, or other nonsteroidal anti-inflammatory drugs;
history of drug or alcohol abuse or dependence.

- Known or suspected pregnancy, or had been pregnant or breastfeeding within past 2
months.

- Has used investigational drug and/or participated in other clinical trial within past
8 weeks.