Oral Contraceptives in the Metabolic Syndrome

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00205504

Enrollment

Registered

2005-09-20

Start date

2005-06-30

Completion date

2009-06-30

Last updated

2018-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Diseases, Insulin Resistance, Metabolic Syndrome X, Obesity

Keywords

Inflammatory markers, oral contraceptions, obesity, metabolic syndrome X

Brief summary

Oral contraceptives (OCs) are the most widely used method of reversible birth control. However, the long-term cardiovascular safety of the widely used low-dose OCs (ethinyl-estradiol \< 50 mcg) is still debated. Although cardiovascular events are rare in young women whether they use OCs or not, the risks of myocardial infarction and ischemic stroke are increased among users of OCs who have conventional cardiovascular risk factors such as use of tobacco, diabetes or hypercholesterolemia. However, the risk of cardiovascular events in OC users with emerging cardiovascular risk factors (such as obesity and the metabolic syndrome) have not been investigated. Recently, the metabolic syndrome has been linked with the risk of cardiovascular disease. The syndrome is a clustering of risk factors in a single individual, and its underlying cause may be insulin resistance. Whether the metabolic syndrome predicts a higher cardiovascular risk in OC users has not been studied. This is a critical problem because the metabolic syndrome is prevalent in 24% of adults. Until the cardiovascular risks in users of OC are clearly defined, the appropriate use of OC with the least harm would not be possible. The investigator's long-term goal is to understand the best way to prevent and treat cardiovascular disease in women. The objective of this particular project is to obtain pilot data on the extent to which the metabolic syndrome and obesity affects glucose metabolism and cardiovascular risks in women taking OCs. The researchers hypothesize that women with metabolic syndrome and obese women will have worsened glucose metabolism and elevated cardiovascular risks associated with OC use, when compared to normal weight women without the metabolic syndrome. Results of this study will clarify the risk factors for cardiovascular events in women taking OCs, and will serve as pilot data for a National Institutes of Health (NIH) proposal. Once the cardiovascular risk factors of OC users are understood, clinicians can make better informed decisions about contraceptive choices for their patients.

Interventions

DRUGOrtho Tri Cyclen

Ortho Tri Cyclen, one tablet daily, for 6 cycles

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 40 Years

Healthy volunteers

Yes

Inclusion criteria

1. Acceptable health based on interview, medical history, physical examination, and laboratory tests (comprehensive metabolic panel - SMA20, and complete blood count - CBC); 2. Have not taken oral contraceptives (OCs) in the past 3 months; 3. Ability to comply with the requirements of the study; 4. Ability and willingness to provide signed, witnessed informed consent. In addition, women with the metabolic syndrome must meet the National Cholesterol Education Program (NCEP) defined criteria of the metabolic syndrome, that is, having at least 3 of the 5 factors: 1. increased waist circumference \> 35 inches, 2. hypertriglyceridemia ≥ 150 mg/dL, 3. low high-density lipoprotein (HDL) cholesterol \< 50 mg/dL in women, 4. hypertension (≥ 130/≥ 85 mmHg), 5. fasting glucose ≥ 100 mg/dL. Obese women with or without the metabolic syndrome should have a Body Mass Index (BMI) \> 30 kg/m2 and lean women should have a Body Mass Index BMI \< 25 kg/m2.

Exclusion criteria

1. Diabetes mellitus by fasting glucose or a 2-hour oral glucose tolerance test (OGTT); 2. Clinically significant pulmonary, cardiac (including but not limited to ischemic heart disease, stable/unstable angina, and congestive heart failure), renal, hepatic, cholestatic, neurologic, psychiatric, infectious, and malignant disease (other than melanoma skin cancer); 3. History of thromboembolism, myocardial infarction, cerebrovascular accident, vascular disease, known coagulopathy, prolonged immobilization, or recent major surgery (within past 6 months); 4. Systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg (mild hypertension is not an exclusion criterion); 5. History of breast cancer, migraine headaches, or age ≥ 35 years and smoker of ≥ 20 cigarettes/day; 6. Use of metformin, thiazolidinediones, anti-hyperlipidemic drugs, anti-hypertensive drugs, glucocorticoids, or anti-androgens (spironolactone, flutamide, etc.) within 3 months; 7. Documented or suspected illicit drug abuse or alcoholism within one year; 8. Ingestion of any investigational drugs within 3 months prior to the study onset; and 9. Pregnancy or lactation (≤ 6 weeks postpartum); 10. Hematocrit \< 33g/dL. These

Design outcomes

Primary

Measure	Time frame	Description
Changes in Insulin Sensitivity Associated With Oral Contraceptive (OC) Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	Insulin sensitivity was assessed by frequent sampling intravenous glucose tolerance test (FSIVGTT).

Secondary

Measure	Time frame	Description
Changes in Lipid Profile Compared Associated With OC Use Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	The lipid profile is assessed through blood sample analysis for low-density lipoprotein (LDL), Triglycerides and high-density lipoprotein (HDL).
Changes in Estrogen Metabolites (Plasma) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	—
Changes in Waist-to-Hip Ratio Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	Waist-to-hip ratio is assessed through calculated ratio of waist and hip circumference.
Inflammatory Marker Changes (MCP-1) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	Inflammatory marker is assessed through blood analysis for Monocyte chemotactic protein-1 (MCP-1).
Inflammatory Marker Changes, High Sensitive C-reactive Protein (Hs-CRP) and Adiponectin, Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	Inflammatory markers are assessed through blood analysis for C-reactive protein (hs-CRP) and adiponectin.
Changes in Body Mass Index (BMI) Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	Body Mass Index is a calculation of height and weight: kg/m²
Changes in Waist Circumference Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	—
Inflammatory Marker Changes, Soluble Vascular Cell Adhesion Molecule (sVCAM) and Soluble Intercellular Adhesion Molecule (sICAM), Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	These inflammatory markers are assessed through blood analysis of Soluble Vascular Cell Adhesion Molecule (sVCAM) and soluble intercellular adhesion molecule (sICAM).
Changes in Blood Pressure Associated With OC Use Compared Among (1) Obese Women and (2) Lean Women	Baseline and 6 months	—

Countries

United States

Participant flow

Pre-assignment details

Although 46 completed informed consent, only 36 initiated the study. Among The participants who did not begin the study were lost to follow-up prior to beginning the protocol, were no shows, or withdrew from the study before beginning study procedures.

Participants by arm

Arm	Count
Obese Women Women with Body Mass Index (BMI) \>30 kg/m². Note: Only two arms were analyzed for the results. Women who were candidates for taking oral contraceptive pills and had the metabolic syndrome could not be recruited. That is because some inclusion criteria for metabolic syndrome are actually exclusion criteria for safe oral contraceptive use.	21
Lean Women Women with Body Mass Index)BMI \<25 kg/m²	15
Total	36

Baseline characteristics

Characteristic	Lean Women	Obese Women	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants	21 Participants	36 Participants
Age, Continuous	21.4 years STANDARD_DEVIATION 2.3	25.3 years STANDARD_DEVIATION 6.9	23.4 years STANDARD_DEVIATION 5.8
Region of Enrollment United States	15 participants	21 participants	36 participants
Sex: Female, Male Female	15 Participants	21 Participants	36 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	— / —	— / —
other Total, other adverse events	2 / 21	2 / 15
serious Total, serious adverse events	1 / 21	0 / 15