This is a double-blinded, randomized, prospective placebo-controlled clinical trial to be conducted within the Mayo Clinic and the Mayo Clinic Health System.

The goal of the research study is to gather information to determine whether Doxycycline is effective for the treatment of unacceptable bleeding associated with the etonogestrel subdermal implant (ESI), as compared to placebo.

ESI is a long-acting reversible contraceptive. Though safety and efficacy have been established world wide, only about 1 % of women have been reported to use this method. Its use is limited by bleeding pattern changes which result in requests for early removal, most commonly within the first 8 months of use.

Women ages 18-51 years, choosing ESI and who meet eligibility criteria, will be offered enrollment in the study at the time of ESI insertion. Every effort will be made to insert Implanon on the same day as consent unless medically contraindicated. Prospective diaries will be completed starting on the date of ESI insertion. All participants will be contacted by study personnel 13 weeks after enrollment and queried as to the presence of unacceptable bleeding. Bleeding concerns will be objectively assessed using a modification of the Pictorial Blood Loss Assessment Chart (PBLAC).

Participants initiating contact with bleeding concerns at any time after 13 weeks post-ESI insertion will be offered treatment randomization at the time of contact. The basis for randomized treatment will be whether the bleeding is considered "unacceptable" to the participant. This is inherently subjective, but constitutes the basis for most removal requests. Participants that report unacceptable bleeding at 13 weeks post-ESI insertion, and those who call with bleeding concerns anytime after 13 weeks post-ESI insertion, will be randomized into one of two groups, Doxycycline or matching placebo.

Participants that do not report unacceptable bleeding will continue to complete diaries and may be eligible for randomized treatment if unacceptable bleeding develops.

Inclusion Criteria:

• Premenopausal women, aged 18-51 years
• Expressed desire for compliance-independent contraception
• No current pregnancy or anticipated desire for childbearing within 3 years of study enrollment and Implanon insertion
• Agreement to participate in all study related procedures and evaluations as documented by a signed informed consent

Exclusion Criteria:

• Current or prior use of Implanon
• Current long-term use of Doxycycline for other indications
• Known structural uterine abnormalities such as polyp, submucosal leiomyoma
• Prior permanent sterilization or endometrial ablation
• Pregnancy or desire for childbearing within 3 years
• Contraindications to or intolerance of etonogestrel
• Allergy to or intolerance of Doxycycline
• Inability or unwillingness to complete study related procedures and evaluations

Adverse Events were collected from baseline (ESI implant) to end of study, approximately 39 weeks.