Obesity and Oral Contraceptive Failure

Obesity Clinical Trial

Official title:

Prenatal Growth Programs Oral Contraceptive Metabolism and Effectiveness

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01944306
• Other study ID #: IRB00009569
• Secondary ID: 2K12HD043488-11
• Status: Terminated
• Start date: August 2013
• Est. completion date: April 2015

Study information

• Verified date: December 2019
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Contraception
• Fetal Growth Retardation
• Infant, Small for Gestational Age
• Obesity

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Cherala G, Thornburg K, Edelman A. Birthweight and cytochrome P4503A4/5 activity in obese women. Br J Clin Pharmacol. 2013 Jan;75(1):275-6. doi: 10.1111/j.1365-2125.2012.04309.x. — View Citation

Edelman A, Cherala G, Lim JY, Jensen JT. Contraceptive failures in overweight and obese combined hormonal contraceptive users. Obstet Gynecol. 2013 Jul;122(1):158-9. doi: 10.1097/AOG.0b013e3182995811. — View Citation

Edelman AB, Carlson NE, Cherala G, Munar MY, Stouffer RL, Cameron JL, Stanczyk FZ, Jensen JT. Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity. Contraception. 2009 Aug;80(2):119-27. doi: 10.1016/j.contraception.2009.04.011. Epub 2009 Jun 4. — View Citation

Edelman AB, Cherala G, Munar MY, Dubois B, McInnis M, Stanczyk FZ, Jensen JT. Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users. Contraception. 2013 Feb;87(2):220-6. doi: 10.1016/j.contraception.2012.10.008. Epub 2012 Nov 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure pharmacokinetic parameters of oral contraceptives including drug clearance.	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.	on day 21 of oral contraceptive use
Secondary	Measure levels of gonadotropins and ovarian hormones	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.	Days 21-25 of oral contraceptive use