Cardiovascular Risk, Insulin Sensitivity, Perimenopausal Disorder
Conditions
Keywords
oral contraceptive, birth control pill, women, healthy volunteer, insulin sensitivity, insulin resistance, cardiovascular risk factors, endothelial function, estrogen metabolism, racial difference, glucose intolerance
Brief summary
Birth control pills are the most commonly used method of birth control. The purpose of this research study is to examine whether birth control pills change heart disease risk and how the body handles blood sugar when given to different women.
Detailed description
The oral contraceptive pill is the most commonly used birth control method. It is debated whether the birth control pill affects how the body handles insulin and sugar, or whether the pill changes heart disease risk. The goal of this study is to evaluate whether certain factors, such as how the body processes hormones, and demographic factors (e.g. body weight and race), influence how the pill affects the handling of insulin and sugar, and heart health.
Interventions
DRUGOrtho Cyclen®
Ethinyl estradiol 35 mcg and norgestimate 0.25 mg (oral) will be taken as one tablet daily for 21 days per month followed by a 7-day pill-free period per cycle. Duration of the study is for 6 cycles of this birth control pill.
Sponsors
American Heart Association
Virginia Commonwealth University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Same drug (orthocyclen) was administered to 2 groups (Caucasian women of reproductive age, and African American women of reproductive age)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal, regular-cycling women 18-35 years * Either African-American or Caucasian (African-American and Caucasian women will be BMI-matched) * non-smoker.
Exclusion criteria
* Diabetes * Clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, and malignant disease * Contraindications to oral contraceptive use (history of blood clots, heart attacks or stroke, vascular disease, coagulopathy, prolonged immobilization, breast cancer, migraine head-aches, major surgery within past 6 months, blood pressure \>160/100 mmHg, pregnancy or lactation) * Use of hormonal contraceptives, glucose-lowering medications, anti-hyperlipidemic, anti-hypertensive or other vasoactive drugs within previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin Sensitivity | Baseline, 6 months | Insulin sensitivity from Frequently sampled IV glucose tolerance test (FSIVGTT), change from baseline to 6 months. Higher values indicate better insulin sensitivity |
| Change From Baseline in Flow-mediated Vasodilatation | Baseline, 6 months | Change Flow-mediated Vasodilatation from baseline to 6 months. Higher values indicate less cardiovascular risk |
| Change From Baseline in Carotid Intima Media Thickness | baseline, 6 months | Change in Carotid Intima Media Thickness from baseline to 6 months, measured on the right carotid artery, posterior. Lower values indicate better cardiovascular risk profile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Insulin at 6 Months | Baseline, 6 months | Higher fasting insulin values indicate an increased metabolic risk |
| Change From Baseline in Fasting Glucose at 6 Months | Baseline, 6 months | Higher fasting glucose indicate an increased metabolic risk |
| Change From Baseline in Areas-under-the-curve for Insulin at 6 Months | Baselines, 6 months | Measured during oral glucose tolerance test. Higher values indicate increased metabolic risk |
| Change From Baseline in Areas-under-the-curve for Glucose | Baseline, 6 months | Measured during oral glucose tolerance test. Higher values indicate increased metabolic risk |
| Change From Baseline in Systolic Blood Pressure at 6 Months | Baseline, 6 months | Higher value indicates increased cardiovascular risk |
| Change From Baseline in Acute Insulin Response to Glucose | Baseline, 6 months | Acute Insulin Response to Glucose values obtained from FSIVGTT models--higher values indicate better insulin response |
| Change From Baseline in Body Mass Index in 6 Months | Baseline, 6 months | Higher values indicate higher metabolic risk |
| Change in Diastolic Blood Pressure From Baseline to 6 Months | Baseline, 6 months | Higher value indicates higher cardiovascular risk |
| Change in LDL From Baseline to 6 Months | Baseline, 6 months | Higher value indicates higher cardiovascular risk |
| Change in Triglycerides From Baseline to 6 Months | Baseline, 6 months | Higher values indicate higher cardiovascular risk |
| Change From Baseline in HDL at 6 Months | Baseline, 6 months | Lower values indicate increased cardiovascular risk |
| Change From Baseline in Glucose Effectiveness | Baseline, 6 months | Obtained from FSIVGTT models--higher values indicate better effectiveness of glucose inducing its own disposition |
| Change From Baseline in Disposition Index at 6 Months | Baseline, 6 months | Modeled from FISVGTT--higher values indicate better glucose disposition |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| African-American Women African-American women
Ortho Cyclen®: Ethinyl estradiol 35 mcg and norgestimate 0.25 mg (oral) took one tablet daily for 21 days per month followed by a 7-day pill-free period per cycle. Duration of the study is for 6 cycles of this birth control pill. | 18 |
| Caucasian Women Caucasian women
Ortho Cyclen®: Ethinyl estradiol 35 mcg and norgestimate 0.25 mg (oral) took one tablet daily for 21 days per month followed by a 7-day pill-free period per cycle. Duration of the study is for 6 cycles of this birth control pill. | 17 |
| Total | 35 |
Baseline characteristics
| Characteristic | African-American Women | Total | Caucasian Women |
|---|---|---|---|
| Age, Continuous | 20.3 years STANDARD_DEVIATION 3.43 | 21.0 years STANDARD_DEVIATION 3.68 | 21.6 years STANDARD_DEVIATION 3.92 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 18 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 17 Participants | 17 Participants |
| Region of Enrollment United States | 18 Participants | 35 Participants | 17 Participants |
| Sex: Female, Male Female | 18 Participants | 35 Participants | 17 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 26 |
| other Total, other adverse events | 0 / 20 | 0 / 26 |
| serious Total, serious adverse events | 0 / 20 | 0 / 26 |
Outcome results
Primary
Change From Baseline in Carotid Intima Media Thickness
Change in Carotid Intima Media Thickness from baseline to 6 months, measured on the right carotid artery, posterior. Lower values indicate better cardiovascular risk profile
Time frame: baseline, 6 months
Population: Data based on images. Some participants images could not be analyzed numerically.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Carotid Intima Media Thickness | -0.00008 mm |
| Caucasian Women | Change From Baseline in Carotid Intima Media Thickness | 0.00118 mm |
Primary
Change From Baseline in Flow-mediated Vasodilatation
Change Flow-mediated Vasodilatation from baseline to 6 months. Higher values indicate less cardiovascular risk
Time frame: Baseline, 6 months
Population: Data based on images. Some participants images could not be analyzed numerically.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Flow-mediated Vasodilatation | 0.0503 mm |
| Caucasian Women | Change From Baseline in Flow-mediated Vasodilatation | -0.0210 mm |
Primary
Change From Baseline in Insulin Sensitivity
Insulin sensitivity from Frequently sampled IV glucose tolerance test (FSIVGTT), change from baseline to 6 months. Higher values indicate better insulin sensitivity
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Insulin Sensitivity | -1.91 min ^ -1 / mIU / L |
| Caucasian Women | Change From Baseline in Insulin Sensitivity | -5.63 min ^ -1 / mIU / L |
Secondary
Change From Baseline in Acute Insulin Response to Glucose
Acute Insulin Response to Glucose values obtained from FSIVGTT models--higher values indicate better insulin response
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Acute Insulin Response to Glucose | -35.6 mIU* L^-1 * min |
| Caucasian Women | Change From Baseline in Acute Insulin Response to Glucose | 0.48 mIU* L^-1 * min |
Secondary
Change From Baseline in Areas-under-the-curve for Glucose
Measured during oral glucose tolerance test. Higher values indicate increased metabolic risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Areas-under-the-curve for Glucose | 443.4 mg/dL * min |
| Caucasian Women | Change From Baseline in Areas-under-the-curve for Glucose | 514.2 mg/dL * min |
Secondary
Change From Baseline in Areas-under-the-curve for Insulin at 6 Months
Measured during oral glucose tolerance test. Higher values indicate increased metabolic risk
Time frame: Baselines, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Areas-under-the-curve for Insulin at 6 Months | 760.6 mIU/mL * min |
| Caucasian Women | Change From Baseline in Areas-under-the-curve for Insulin at 6 Months | 1062.1 mIU/mL * min |
Secondary
Change From Baseline in Body Mass Index in 6 Months
Higher values indicate higher metabolic risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Body Mass Index in 6 Months | -0.32 Kg/m2 |
| Caucasian Women | Change From Baseline in Body Mass Index in 6 Months | 0.39 Kg/m2 |
Secondary
Change From Baseline in Disposition Index at 6 Months
Modeled from FISVGTT--higher values indicate better glucose disposition
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Disposition Index at 6 Months | -911.73 AIRG * Si |
| Caucasian Women | Change From Baseline in Disposition Index at 6 Months | -834.53 AIRG * Si |
Secondary
Change From Baseline in Fasting Glucose at 6 Months
Higher fasting glucose indicate an increased metabolic risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Fasting Glucose at 6 Months | -0.4 mg/dL |
| Caucasian Women | Change From Baseline in Fasting Glucose at 6 Months | 03 mg/dL |
Secondary
Change From Baseline in Fasting Insulin at 6 Months
Higher fasting insulin values indicate an increased metabolic risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Fasting Insulin at 6 Months | 1.66 uIU/ mL |
| Caucasian Women | Change From Baseline in Fasting Insulin at 6 Months | 1.45 uIU/ mL |
Secondary
Change From Baseline in Glucose Effectiveness
Obtained from FSIVGTT models--higher values indicate better effectiveness of glucose inducing its own disposition
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Glucose Effectiveness | -0.0255 1000 * min ^ -1 |
| Caucasian Women | Change From Baseline in Glucose Effectiveness | -0.0078 1000 * min ^ -1 |
Secondary
Change From Baseline in HDL at 6 Months
Lower values indicate increased cardiovascular risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in HDL at 6 Months | 6.8 mg/dL |
| Caucasian Women | Change From Baseline in HDL at 6 Months | 6.9 mg/dL |
Secondary
Change From Baseline in Systolic Blood Pressure at 6 Months
Higher value indicates increased cardiovascular risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change From Baseline in Systolic Blood Pressure at 6 Months | 2.5 mmHg |
| Caucasian Women | Change From Baseline in Systolic Blood Pressure at 6 Months | -1.4 mmHg |
Secondary
Change in Diastolic Blood Pressure From Baseline to 6 Months
Higher value indicates higher cardiovascular risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change in Diastolic Blood Pressure From Baseline to 6 Months | 0.6 mmHg |
| Caucasian Women | Change in Diastolic Blood Pressure From Baseline to 6 Months | 2.44 mmHg |
Secondary
Change in LDL From Baseline to 6 Months
Higher value indicates higher cardiovascular risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change in LDL From Baseline to 6 Months | 13.4 mg/dL |
| Caucasian Women | Change in LDL From Baseline to 6 Months | 17.1 mg/dL |
Secondary
Change in Triglycerides From Baseline to 6 Months
Higher values indicate higher cardiovascular risk
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American Women | Change in Triglycerides From Baseline to 6 Months | 13.3 mg/dL |
| Caucasian Women | Change in Triglycerides From Baseline to 6 Months | 29.3 mg/dL |