Impact of Combined Hormonal Contraceptives on UPA

Phase 4

Completed

Interventions: Drug: Ulipristal Acetate
Drug: Levonorgestrel (LNG)/Ethinyl estradiol birth control pill

Brief Summary: The purpose of this research study is to determine if taking a birth control pill effects how well an emergency contraceptive pill called Ulipristal acetate (UPA) works. This type of emergency contraceptive is the most effective oral method available. However, this medication is an anti-progestin and most regular forms of birth control contain progestin (a female hormone). It is unknown if taking the two close together may make the emergency contraceptive not work well. The overall goal of this research is to improve the effectiveness of contraception for women and to better counsel women.

Detailed Description: Emergency contraception (EC) provides women with an additional line of defense against unintended pregnancy during an act of unprotected intercourse. An antiprogestin, ulipristal acetate (UPA; ellaTM), has emerged as one of the most effective oral options. However, there is currently a lack of information regarding the practical use of UPA. Basic science studies have shown that UPA binds to and prevents progesterone receptor from working, leading to the possible concern that hormonal contraceptives, like the birth control pill, would prevent UPA from working. Ideally, women should start their regular method of birth control soon after EC use but by doing this, they may prevent the UPA EC from working. A woman could just delay starting her regular method of birth control but then she is still at risk for pregnancy.

This proposal has been designed to address this gap in knowledge and will focus on the impact of the birth control pill on UPA's ability to delay ovulation (or the release of an egg). Subjects will undergo a referent cycle UPA only (Cycle 1, 1 month), followed by a washout cycle (Cycle 2, 1 month) and finally UPA with combined oral contraceptives (COCs) dosed 2 days later (Cycle 3, 1 month treatment cycle). The hypothesis is that starting the birth control pill shortly after UPA adversely impacts UPA's ability to delay ovulation.

Recruitment & Eligibility

Inclusion Criteria

Generally healthy women aged 18 to 35 with regular menses (every 21-35 days).
Normal BMI
Proven ovulation with a screening serum progesterone of >3ng/mL
Willing to use condoms (if sexually active with a male partner), willing to not have sex with men during the study, or have had a tubal ligation (or have a partner who has had a vasectomy) or have a copper intrauterine device (IUD).

Exclusion Criteria

Known intolerance or allergy to any of the study medication
Known metabolic disorders including polycystic ovarian syndrome or uncontrolled thyroid disorder
Overweight or obese BMI
Any Centers for Disease Control and Prevention (CDC) Medical eligibility criteria category 3 or 4 for combined oral contraception (COC) use 12.
Pregnancy, breastfeeding, or seeking pregnancy; recent (8 week) use of hormonal contraception
Current use of drugs that interfere with metabolism of sex steroids
Smokers.

Arm && Interventions

Group	Intervention	Description
UPA + COC	Levonorgestrel (LNG)/Ethinyl estradiol birth control pill	During the second treatment month, 1 dose of the study medication ulipristal acetate (UPA) will be given when the follicle is a certain size (approximately cycle day 10) and then 2 days later start birth control pills. Following this, there will be daily study visits for 7 days unless evidence of ovulation occurs earlier.
UPA Only	Ulipristal Acetate	During the first treatment month, 1 dose of the study medication ulipristal acetate (UPA) will be given when the follicle is a certain size (approximately cycle day 10). Following this, there will be daily study visits for 7 days unless evidence of ovulation occurs earlier.
UPA + COC	Ulipristal Acetate	During the second treatment month, 1 dose of the study medication ulipristal acetate (UPA) will be given when the follicle is a certain size (approximately cycle day 10) and then 2 days later start birth control pills. Following this, there will be daily study visits for 7 days unless evidence of ovulation occurs earlier.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Follicle Rupture	within 5 days of taking the study drug	Following dosing with UPA, subjects underwent daily visits with ultrasound monitoring until evidence of follicle rupture (complete disappearance or \>50% reduction of the mean size of the leading follicle).

Secondary Outcome Measures