Pharmacogenomics of Contraception: Genetic Variants and Etonogestrel Pharmacokinetics

NCT03092037 | Completed

• 1 other identifier: 16-2462
• Study Type: observational
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study will investigate the relationship between genetic variants and serum contraceptive hormone levels, specifically the progestin etonogestrel. This study will provide the foundation for future pharmacogenomic investigations of more commonly used contraceptive methods with higher failure rates.

Conditions

Contraception

Outcome Measures

Primary Outcomes (2)

• Proportion of genetic variants in cases versus controls

  Genetic variants will be analyzed using a Taqman microarray chip for 120 pre-selected variants

  DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 12 months.

• Genome wide genotyping results

  Participants will undergo genotyping using a custom MEGA chip at the Colorado Center for Personalized Medicine. Imputation of the chip results will be performed.

  DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 15 months.

Study Arms (2)

All participants

All participants will have their blood drawn. DNA will be extracted from whole blood, and serum will be analyzed for ENG concentrations. Genotyping data will be analyzed for associations with serum ENG concentrations.

Procedure: Blood draw

All participants (side-effects)

All participants will have their blood drawn and complete a brief questionnaire regarding bleeding patterns and side-effects. DNA will be extracted from whole blood and genotyping data will be analyzed for associations with specific bleeding patterns and side-effects.

Procedure: Blood draw

Interventions

Blood draw PROCEDURE

The Investigators will collect serum and whole blood from participants.

All participants; All participants (side-effects)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Eligible participants must be females as we are studying the ENG contraceptive implant.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

We will enroll 900 women of reproductive age (18-45 years) who have had an ENG contraceptive implant in place for 12-36 months.

You may qualify if:

• women of reproductive age (18-45 years)
• have had an ENG contraceptive implant in place for 12-36 months

You may not qualify if:

• Use of medications or supplements in the past four weeks which could impact serum ENG levels through inhibition or induction of CYP enzymes (specifically CYP-3A4)
• Medical conditions that could impact baseline liver function (e.g. hepatitis, cirrhosis)
• Body mass index (BMI) less than 18.5

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Society of Family Planning: collaborator

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (7)

• Lazorwitz A, Aquilante CL, Shortt JA, Gignoux CR, Teal S, Sheeder J. Pharmacogenomics of the Etonogestrel Contraceptive Implant: A Genome-Wide Association Study of Steady-State Etonogestrel Concentrations. O G Open. 2025 Feb 27;2(1):e066. doi: 10.1097/og9.0000000000000066. eCollection 2025 Feb.

  PMID: 41000562 DERIVED

• Lazorwitz A, Sheeder J, Teal S. The influence of lifestyle factors on serum etonogestrel concentrations among contraceptive implant users. Contraception. 2024 Dec;140:110539. doi: 10.1016/j.contraception.2024.110539. Epub 2024 Jul 11.

  PMID: 39002624 DERIVED

• Lazorwitz A, Sheeder J, Teal S. Variability in repeat serum etonogestrel concentrations among contraceptive implant users during the steady-release pharmacokinetic period. Contraception. 2022 Apr;108:65-68. doi: 10.1016/j.contraception.2021.12.008. Epub 2021 Dec 29.

  PMID: 34973207 DERIVED

• Lazorwitz A, Aquilante CL, Shortt JA, Sheeder J, Teal S, Gignoux CR. Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception. Clin Transl Sci. 2021 Sep;14(5):1713-1718. doi: 10.1111/cts.13014. Epub 2021 May 2.

  PMID: 33650294 DERIVED

• Lazorwitz A, Sheeder J, Teal S. An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users. Eur J Contracept Reprod Health Care. 2021 Aug;26(4):323-325. doi: 10.1080/13625187.2021.1887475. Epub 2021 Feb 17.

  PMID: 33596152 DERIVED

• Lazorwitz A, Aquilante CL, Sheeder J, Guiahi M, Teal S. Relationship between patient characteristics and serum etonogestrel concentrations in contraceptive implant users. Contraception. 2019 Jul;100(1):37-41. doi: 10.1016/j.contraception.2019.03.045. Epub 2019 Apr 10.

  PMID: 30980827 DERIVED

• Lazorwitz A, Aquilante CL, Oreschak K, Sheeder J, Guiahi M, Teal S. Influence of Genetic Variants on Steady-State Etonogestrel Concentrations Among Contraceptive Implant Users. Obstet Gynecol. 2019 Apr;133(4):783-794. doi: 10.1097/AOG.0000000000003189.

  PMID: 30870275 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples will be collected at the enrollment visit and will undergo DNA extraction using commercial Qiagen® kits in Dr. Christina Aquilante's laboratory.

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Aaron Lazorwitz, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 27, 2017
• Study Start: March 23, 2017
• Primary Completion: April 29, 2022
• Study Completion: April 29, 2022
• Last Updated: August 16, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)