Does Concomitant Use of Combined Oral Hormonal Steroids Stop Bleeding in Women Using Etonogestrel Implants (Implanon/Nexplanon®)?: A Randomized Controlled Study

The etonogestrel (ENG) contraceptive implant (Implanon/Nexplanon®), is a silicone- free,
single rod subdermal contraceptive implant that contains 68 mg of etonogestrel, is approved
for use for three years, and is one of the most effective forms of contraception available
(1). ENG contraceptive implants are easily inserted and removed (1,2), offer quick return to
fertility (2), are cost-effective and cost-saving (3,4) and offer non-contraceptive benefits
such as improvement in pain for patients with complaints of dysmenorrhea (5).

Hypothesis: Women using ENG contraceptive implants who report a bleeding-spotting episode of
at least seven days will be more likely to stop bleeding within 3 days of beginning a 14-day
course of combined oral hormonal steroids compared to women receiving 14 days of placebo.

Inclusion Criteria:

- All female

- English or Spanish speaking women

- between the ages of 18-44

- using an ENG contraceptive implant who complain of bothersome bleeding and have a
current bleeding episode of at least seven days will be invited to participate.

Exclusion Criteria:

- Category 3 or 4 contraindications to estrogen therapy according to the Centers for
Disease Control 2010 Medical Eligibility Criteria.

- Category 3 contraindications: less than 1 month postpartum if breastfeeding, less
than 21 days postpartum if not breastfeeding, history of Deep Vein Thrombosis (DVT)
/Pulmonary Embolism (PE) not on anticoagulant therapy and no risk factors, Deep
venous thrombosis/Pulmonary Embolus on established anticoagulant therapy and no risk
factors, history of malabsorptive bariatric surgery, greater than or equal to months
post peripartum cardiomyopathy with normal to mildly impaired cardiac function,
greater than or equal to 35 years old with less than 15 cigarettes smoked per day,
multiple risk factors for arterial cardiovascular disease, adequately controlled
hypertension, blood pressure 140-159/90-99 mm Hg, migraines without aura less than 35
years old, past breast cancer and no evidence of recurrent disease for 5 years,
diabetes with retinopathy, neuropathy, nephropathy (category 3 or 4 depending on
severity), diabetes greater than 20 years duration or associated with other vascular
disease, medically treated symptomatic gallbladder disease or current symptomatic
gallbladder disease, past combined oral contraceptive pill related cholestasis, acute
viral hepatitis, hepatocellular adenoma, hepatoma, use of ritonavir-boosted protease
inhibitors, anticonvulsant therapy use including phenytoin, carbamazepine,
barbiturates, primidone, topiramate, oxcarbazepine, and lamotrigine, use of
Rifampicin,

- Category 4 contraindications: less than 6 months post peripartum cardiomyopathy with
normal to mildly impaired cardiac function, any time following peripartum
cardiomyopathy with moderately to severely impaired cardiac function, greater than or
equal to 35 years old with greater than 15 cigarettes smoked per day, multiple risk
factors for arterial cardiovascular disease, blood pressure greater than or equal to
160/100 mm Hg, high risk for recurrent DVT/PE, acute DVT/PE, DVT/PE and on
established anticoagulant therapy with greater than or equal to 1 risk factor for
recurrent DVT/PE, major surgery/prolonged immobilization, known thrombogenic
mutations, current and history of ischemic heart disease, history of stroke,
complicated valvular heart disease, systemic lupus erythematosus (SLE) with positive
or unknown antiphospholipid antibodies, migraines without aura greater than or equal
to 35 years old, migraines with aura at any age, current breast cancer, complicated
solid organ transplantation

- Body mass index (BMI) greater than 35.

- A systolic blood pressure greater than 135 on more than 2 occasions. assuring the
measurements are separated by an interval of at least 15 minutes.

- A diastolic blood pressure greater than 85 on more than 2 occasions. assuring the
measurement are separated by an interval of at least 15 minutes.

- A positive pregnancy test.

- A positive chlamydia test.

- Unable or unwilling to swallow pills.

- A medical condition deemed severed by a physician investigator.

- A participant taking a liver enzyme inducing drug.

- A known allergy to levonorgestrel or ethinyl estradiol.

- An abnormal speculum exam (i.e. bleeding ectropion or cervical mass).

- Does not meet appropriate cervical cytology screening guidelines.

- Cervical procedure done in the past 3 months.

- On a concurrent hormonal contraceptive and unwilling to discontinue.

- Breast lesions