Effects of Hormonal Contraceptives on Liver Proteins and Coagulation Factors: A Comparison of a Contraceptive Vaginal Ring and an Oral Contraceptive

The purpose of this 3-month (cycle) study was to evaluate the effects of hormonal contraceptives containing a progestin and an estrogen on liver proteins and coagulation factors that are sensitive to estrogen. In this study, a contraceptive vaginal ring containing Nestorone® (a progestin with no androgenic properties) and ethinyl estradiol was compared to an oral contraceptive containing levonorgestrel (an androgenic progestin) and ethinyl estradiol.

The purpose of this 3-month (cycle) study was to evaluate the effects of hormonal contraceptives containing a progestin and an estrogen on liver proteins and coagulation factors that are sensitive to estrogen. In this study, a contraceptive vaginal ring containing Nestorone® (a progestin with no androgenic properties) and ethinyl estradiol was compared to an oral contraceptive containing levonorgestrel (an androgenic progestin) and ethinyl estradiol.

Eligibility Criteria:
Inclusion Criteria:

* Healthy women, aged 18-34 years, who did not wish to become pregnant for 3 months (or 5 months if first discontinuing oral contraceptives
* Intact uterus and at least 1 ovary
* Have regular menstrual cycles (28 ± 7 days) or 2 regular cycles after parturition or abortion
* Willing to use condoms while having sexual intercourse during the 3 month study (or 5 months if discontinuing oral contraceptives), or
* Willing to continue use of a specified non-hormonal method of birth control including permanent sterilization, non-hormone-containing IUD, male condoms, or abstinence during the study or to use condoms if discontinuing one of these methods
* Willing and able to comply with the protocol
* Willing and able to sign informed consent prior to entry into the study and prior to discontinuing another method of contraception
* Easy venous access

Exclusion Criteria:

* Pregnancy
* Known hypersensitivity to estrogens or progestins
* Known hypersensitivity to silicone rubber
* Undiagnosed vaginal discharge or vaginal lesions or abnormalities
* Smoking status: \>15 cigarettes per day
* Breastfeeding
* Current or past thrombophlebitis or thromboembolic disorders
* Family history of venous thrombosis or embolism (1st degree relatives \<55 years of age)
* Known history of Factor V Leiden or positive screening test for APC-resistance
* Current or past cerebrovascular or coronary artery disease
* Carcinoma (hormone-dependent tumor; past history of any carcinoma not in remission for \>5 years)
* Medically diagnosed severe depression
* Headaches with focal neurological symptoms
* Undiagnosed abnormal genital bleeding
* History of cholestatic jaundice of pregnancy or jaundice with prior steroid use
* Benign or malignant liver tumors; active liver disease
* Diastolic/systolic BP ≥90/140 mmHg after 5 min. rest
* Known or suspected alcoholism (\>2 drinks/day)or drug abuse
* Positive for hepatitis B \& C and/or HIV 1 or 2, abnormal screening CBC, serum chemistry values (including fasting, total cholesterol and triglycerides), abnormal Pap smear, abnormal findings on dipstick urinalysis, or an abnormal electrocardiogram (ECG)
* Participation in a clinical trial within last 3 months or more than 1 trial in the last year
* BMI (kg/m2) \>28
* Use of injectable contraceptives in last 6 months (e.g. cyclofem or DMPA)
* Unwilling to stop oral contraceptives for 2 months prior to study initiation
* Use of implanted hormonal contraceptives, including Mirena or Implanon, in last 2 years
* Not living in the catchment area of the clinic\*Severe cystoceles or rectoceles