Effects of Obesity on Pharmacokinetics of the Levonorgestrel Emergency Contraceptive Pill

Pharmacokinetics of the Levonorgestrel-only Emergency Contraception Regimen in Normal-weight, Obese and Extremely Obese Users: a Pilot Study

The purpose of this study is to determine the effects of obesity on the pharmacokinetics of the levonorgestrel (LNG) only emergency contraceptive (EC) regimen and on markers of ovulation

Primary hypothesis:

1) Obese users of LNG-EC have a pharmacokinetic profile that is consistent with a larger volume of distribution of LNG.

Secondary hypothesis:

1. Alterations in these pharmacokinetic parameters of the LNG-EC regimen in obese women affect the primary mechanism of action, which is inhibition of ovulation.
2. Obesity may affect other factors that alter levels of LNG, such as sex-hormone binding globulin (SHBG) and albumin, which bind LNG and potentially lowers the amount of free LNG.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Levonorgestrel 1.5mg by mouth once

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Non-smoking women between ages 18-35 years with regular menstrual cycles (24-35 days) will be enrolled, to include 10 normal weight (BMI = 18.5-24.9 kg/m2) women, 10 obese (BMI = 30-39.9 kg/m2) and 10 extremely obese (BMI ≥ 40 kg/m2) women

Description

Inclusion Criteria:

• Women between ages 18-35 years

  • Regular menstrual cycles (24-35 days) for the past 2 months
  • Ovulatory at defined by midluteal progesterone level >3 ng/mL (Day 18-25)
  • Belongs to one of the following categories: normal weight (BMI = 18.5-24.9 kg/m2), obese (BMI = 30-39.9 kg/m2) or extremely obese (BMI ≥ 40 kg/m2)
  • Participant has no intention of or desire to conceive (e.g., active attempt to become pregnant or in vitro fertilization) for the duration of the study
  • Participant agrees to consistently use an effective method of nonhormonal contraception throughout the duration of study, which could include: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, non-hormonal intra-uterine devise (IUD), or sterilization.
  • Able to give informed consent

Exclusion Criteria:

• • Known renal or liver disease

  • Known pituitary disorder
  • Known adrenal disorder
  • Known thyroid disorder
  • Use of medication known to alter the cytochrome P450 system
  • Use of depot-medroxyprogesterone acetate in the previous 6 months or any other hormonal contraceptive in the previous 3 months
  • Currently breastfeeding
  • Pregnant
  • Pregnancy in the prior month
  • Known allergy to medication
  • Other specific contraindications to LNG EC

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal weight women; Levonorgestrel 1.5mg by mouth once	Drug: Levonorgestrel 1.5mg by mouth once; Levonorgestrel 1.5mg by mouth given on menstrual cycle day 8; Other Names: Plan B One Step; Next Choice One Dose
Obese women; Levonorgestrel 1.5mg by mouth once	Drug: Levonorgestrel 1.5mg by mouth once; Levonorgestrel 1.5mg by mouth given on menstrual cycle day 8; Other Names: Plan B One Step; Next Choice One Dose
Extremely obese women; Levonorgestrel 1.5mg by mouth once	Drug: Levonorgestrel 1.5mg by mouth once; Levonorgestrel 1.5mg by mouth given on menstrual cycle day 8; Other Names: Plan B One Step; Next Choice One Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax)	Time 0, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum concentration (Tmax)	0, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours
Minimum concentration (Cmin)	Time 0, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours
Area under the concentration time-curve (AUC)	Time 0, 1, 2, 3, 4, 6, 8, 12, 6, 24, 48, 72 hrs

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Society of Family Planning
• Investigators: Principal Investigator: M Natavio, University of Southern California

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: April 1, 2014
• First Posted (Estimate): April 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Obesity; Emergency contraception; Levonorgestrel emergency contraception
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Emergencies; Obesity; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: HS-12-00602