UMPALA is a research study to look at the effect of four different, approved contraceptives on the cervical and vaginal tissues as well as on factors in the blood. Participants will have a baseline examination then receive one of four approved, marketed contraceptive products. Cervico-vaginal assessments will take place 4 weeks after contraceptive initiation and 3 months after to assess changes in mucosal safety after use of various contraceptive products in young, healthy, HIV uninfected women.

This clinical study will complete approximately 12 healthy, non-pregnant, HIV-uninfected women aged 18-50 years per contraceptive arm, who are at low risk for sexually transmitted infections (STIs) at two clinical sites, for a total of approximately 96 completed participants. The study will examine changes from baseline, pre-contraceptive dosing to post contraceptive dosing of cervico-vaginal mucosal safety and adverse events.

Participants at each site will be randomized (1:1:1:1) to one of four, marketed, approved contraceptive dosing forms: Levonorgestrel (LNG) 52 mg. Intrauterine System (IUS), Copper Intrauterine Device (IUD), etonogestrel (ETG, Nexplanon, Implanon) contraceptive implant, or DMPA SC contraceptive injection.

Enrollment is expected to take approximately 8 months and each participant is expected to complete the study within 4 months.

Inclusion Criteria:

• Age 18 to 50 years, inclusive
• In general good health without any significant systemic disease and with an intact uterus and cervix.
• History of Pap smears and follow-up consistent with standard, local clinical practice or willing to undergo a Pap smear at Visit 1
• Willing to give voluntary consent and sign an informed consent form
• Willing and able to comply with protocol requirements, including accepting randomization to study contraceptive products
• If currently on a contraceptive product, willing to go off products and use condoms for birth control for a specified time
• If in a relationship, must be with a partner who is not known to be HIV positive and has no know risk of sexually transmitted infections (STIs)

Exclusion Criteria:

• Positive pregnancy test or plans to become pregnant during the course of the study
• Currently exclusively breastfeeding or planning to exclusively breastfeed during the course of the study
• Less than six weeks from a delivery of an infant greater than 20 weeks gestation
• Use of DMPA in the past 4 months
• Clinical signs and symptoms of menopause
• Current WHO or CDC medical eligibility criteria level 3 or 4 for any contraceptive product to which a participant could receive at the clinical site
• History of sensitivity/allergy to any component of the study product, topical anesthetic, or to both silver nitrate and Monsel's solution
• Current infection with Trichomonas vaginalis (TV), Neisseria gonorrhea (NG), Chlamydia trachomatis (CT)
• Current positive test for HIV
• History of a pulmonary embolus or deep vein thrombosis
• Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc)
• Known blood disorder, eg. von Willebrands disease, that could lead to prolonged or continuous bleeding with biopsy
• Chronic use systemic corticosteroids, antibiotics, antimycobacterials, anticoagulants or other drugs known to prolong bleeding and/or promote clotting, antifungals, or antivirals or antiretrovirals.
• Current or anticipated chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for the duration of the study
• Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
• Abnormal finding on laboratory or physical examination or a social or medical condition in which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of the data