Obesity and Oral Contraceptive Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01944306
Recruitment Status : Terminated (Due to lack of funds, the study has been terminated upon recruiting less than desired number of subjects)
First Posted : September 17, 2013
Last Update Posted : April 17, 2015
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Ganesh Cherala, Oregon Health and Science University

Brief Summary:

Contraceptive failure is the primary cause of unintended pregnancy in the United States. With obesity rates at epidemic proportions, any association between obesity and strategies that prevent undesired pregnancies constitutes a significant public health and economic concern. Evidence from recent epidemiological studies and our preliminary data (sub-therapeutic levels of steroid hormones due to drug clearance and half-life) suggest that obesity reduces oral contraceptive efficacy. Furthermore, preliminary analysis suggested that a sub-group of obese women, defined by their own birth weight, are at higher risk of contraceptive failure. Further studies are necessary to investigate whether birth weight, a surrogate marker of in utero growth restriction, is a useful diagnostic marker for the identification of women prone to contraceptive failure. Such an understanding is critical to finding a contraceptive strategy with better efficacy for these women.

The overall goal of this project is to test pharmacokinetics of oral contraceptive agents in obese women with low birth weight and compare to obese women with normal birth weight. The main hypothesis for this proposal is that an adverse in utero environment programs the expression and function of enzymes and transporters that underlie pharmacokinetics of oral contraceptives, and leads to contraceptive failure.

Reproductive-aged, ovulatory women of obese BMI >30 kg/m2 with normal birth weight (5.5-8 lbs; n=10) and low birth weight (<5.5 lbs; n=10), will be placed on oral contraceptives for 1 month. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (luteinizing hormone, follicle-stimulating hormone) and ovarian hormone levels (estradiol, progesterone) will be monitored.

Condition or disease
Contraception Fetal Growth Retardation Infant, Small for Gestational Age Obesity

Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prenatal Growth Programs Oral Contraceptive Metabolism and Effectiveness
Study Start Date : August 2013
Actual Primary Completion Date : April 2015
Estimated Study Completion Date : December 2015

Low birth-weight, obese
Low birth-weight, normal body weight
Normal birth-weight, obese
Normal birth-weight, normal body weight

Primary Outcome Measures :
  1. Measure pharmacokinetic parameters of oral contraceptives including drug clearance. [ Time Frame: on day 21 of oral contraceptive use ]
    Serum concentration-time data for each subject will be analyzed using a non-compartmental model assumption. Serum concentrations below the lower limit of quantitation (LLOQ) at the beginning and end of the profile will be set to zero. Serum concentration-time profiles will be summarized using descriptive statistics and graphical display. Student t-tests will be used to test whether the average values of each of the pharmacokinetic parameters, including free concentrations, differ between the four groups of women.

Secondary Outcome Measures :
  1. Measure levels of gonadotropins and ovarian hormones [ Time Frame: Days 21-25 of oral contraceptive use ]
    To compare gonadotopin levels, average leutinizing hormone and follicle stimulating hormone levels measured for days 21-25 will be calculated. In addition, the follicle stimulating hormone/leutinizing hormone ratio will be calculated at each time point. The average levels of these measures will then be compared between the four groups of women using a student's t-test.

Biospecimen Retention:   Samples With DNA
Blood, Plasma, and Urine will be collected for the analaysis of drug levels and genotyping of various genes that could explain pharmacokinetics of oral contraceptives.

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Reproductive-aged, ovulatory women seeking to initiate contraception with combined oral contraceptives will be recruited from the female population of the Portland, OR area. Subjects must have access to their birth weight record. Enrollment will be confined to women who have not used a hormonal contraceptive method for 30 days or more prior to enrollment.

Inclusion Criteria:

  • age 18 to 35.
  • single progesterone level of 3 ng/mL or greater during the luteal phase (days 18 to 25) in the menstrual cycle prior to dosing with oral contraceptives.

Exclusion Criteria:

  • absolute/relative contraindications to ethinyl estradiol and levonorgestrel.
  • impaired liver function.
  • history of deep venous thrombosis.
  • hypertension (> 140/90).
  • diabetes with vascular changes.
  • migraines with aura or neurological changes.
  • history of myocardial infarction, pulmonary embolus, stroke or breast cancer.
  • anemia (hematocrit < 36%).
  • actively seeking or involved in a weight loss program (must be weight stable)
  • pregnancy, breastfeeding, or seeking pregnancy.
  • diagnosis of Polycystic Ovarian Syndrome.
  • recent (4 week) use of hormonal contraceptives (patch or ring included), intrauterine, or implantable hormonal contraception.
  • DepoProvera use within six months.
  • current use of drugs that interfere with metabolism of sex steroids.
  • smokers.
  • uncontrolled thyroid dysfunction.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01944306

United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Ganesh Cherala, PhD Oregon Health and Science University

Responsible Party: Ganesh Cherala, Assistant Professor, Oregon Health and Science University Identifier: NCT01944306     History of Changes
Other Study ID Numbers: IRB00009569
2K12HD043488-11 ( U.S. NIH Grant/Contract )
First Posted: September 17, 2013    Key Record Dates
Last Update Posted: April 17, 2015
Last Verified: April 2015

Keywords provided by Ganesh Cherala, Oregon Health and Science University:
Pharmacology, Clinical
Drug Efficacy
Drug Failure
Contraceptive Agents

Additional relevant MeSH terms:
Fetal Growth Retardation
Nutrition Disorders
Body Weight
Signs and Symptoms
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Contraceptive Agents
Contraceptives, Oral
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female