Oral Contraceptive Pill (OCP) Pharmacogenomics

Influence of Genetics Variants on the Pharmacokinetics and Pharmacodynamics of Combined Oral Contraceptive Pill Users

The goal of this clinical trial is to evaluate how differences in specific parts of our DNA can influence how individual bodies break down the hormones contained within oral contraceptive pills, which could affect how well these birth control pills work to prevent pregnancy. The investigators are also interested in exploring how these differences in our DNA can also explain why patients taking the exact same formulation of birth control pill will experience very different side effects. The main questions it aims to answer are:

• Do individuals with the CYP3A7*1C variant have increased metabolism of both desogestrel and ethinyl estradiol when taking a combined oral contraceptive pill?
• Do individuals with the CYP3A7*1C variant experience higher rates of breakthrough ovulation while taking a desogestrel/ethinyl estradiol combined oral contraceptive pill?
• What novel genetic loci are associated with alterations in steroid hormone pharmacokinetics and pharmacodynamics among a larger cohort of combined oral contraceptive pill users?

Participants will take a specific formulation of combined oral contraceptive pill (desogestrel/ethinyl estradiol) and undergo the following procedures:

• Blood draw to measure the amount of progestin and estrogen in their system from the combined oral contraceptive pill
• Questionnaires to assess side effects possibly caused by the combined oral contraceptive pill
• Blood draw to measure endogenous hormone levels and biomarkers that may be affected by the combined oral contraceptive pill
• A transvaginal ultrasound to measure any ovarian follicles (optional procedure)

Study Overview

• Status: Recruiting
• Conditions: Contraception; Pharmacogenomic Drug Interaction
• Intervention / Treatment: Drug: Desogestrel / Ethinyl Estradiol Pill

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Aaron M Lazorwitz, MD, PhD; Phone Number: 2037854688; Email: aaron.lazorwitz@yale.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • University of Colorado Anschutz Medical Campus
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: AmberJean Hansen; Phone Number: 203-737-7962; Email: BirthControlGene@yale.edu
      • Principal Investigator: Aaron Lazorwitz, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Female, aged 18-45 years old
4. In good general health as evidenced by medical history and no need for regular intensive medical interventions (e.g., inpatient admissions, surgical treatments). The Principal Investigator will be responsible for determining good general health for potential participants with complicated medical histories.
5. Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen
6. Body-mass index ≥18.5kg/m2
7. Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort) during the study
8. Normal blood pressure measurement at study screening
9. Negative urine pregnancy test at study screening

Exclusion Criteria:

1. Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort)43
2. Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis)

3. Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42)

   1. Current breast cancer or personal history of breast cancer
   2. Severe decompensated cirrhosis
   3. Personal history of deep venous thrombosis or pulmonary embolism
   4. Recent major surgery with prolonged immobilization
   5. Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease
   6. Current gallbladder disease
   7. Migraine headaches with aura
   8. History of malabsorptive bariatric surgery
   9. History of cholestasis due to past oral contraceptive pill use
   10. Personal history of hypertension
   11. Personal history of ischemic heart disease
   12. Known thrombogenic mutations
   13. Personal history of focal nodular hyperplasia of the liver, hepatocellular adenoma, or malignant hepatoma
   14. Multiple sclerosis with prolonged immobility
   15. History of peripartum cardiomyopathy
   16. Current tobacco smoker and age ≥35 years
   17. History of complicated solid organ transplantation
   18. Personal history of stroke
   19. Personal history of superficial venous thrombosis
   20. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies
   21. Complicated valvular heart disease
   22. Current use of fosamprenavir or lamotrigine
4. Use of injectable contraceptive method within 6 months or current use of an ENG implant
5. Childbirth within 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined oral contraceptive pill users; Administered a combined oral contraceptive pill containing desogestrel and ethinyl estradiol (Desogen, 0.15mg desogestrel and 0.03mg ethinyl estradiol per active pill) for at least one cycle (21 days) and up to 13 total cycles (one year)	Drug: Desogestrel / Ethinyl Estradiol Pill; Standard pill packs containing 21 active pills and 7 placebo pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum etonogestrel concentration	Pharmacokinetic measurement for progestin	Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)
Serum ethinyl estradiol concentration	Pharmacokinetic measurement for estrogen	Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum estradiol concentration	Pharmacodynamic measurement of endogenous estrogen	Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Serum progesterone concentration	Pharmacodynamic measurement of endogenous progesterone	Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Modified Hoogland score	Calculated based on serum estradiol, serum progesterone, and follicle-like structures. found on transvaginal ultrasound. Scores range from 1 to 5, with a higher score indicating a higher likelihood of pending ovulation with a score of 5 indicating suspected ovulation	Measured on Cycle 1, Day 22 (optional study procedure) (each cycle is 28 days)
Positive and Negative Affect Scheduled	Questionnaire designed to assess current affect. Scores range from 10-50 for positive affect items and 10-50 for negative affect items, with higher scores representing more positive affect or negative affect, respectively.	Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeated measurements again in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Sex hormone binding globulin levels	Marker of estrogenicity	Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)
Serum albumin concentration	Protein binding compound	Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Aaron M Lazorwitz, MD, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Contraceptive Agents, Hormonal; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Estrogens; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Progestins; Estradiol; Ethinyl Estradiol; Desogestrel
• Other Study ID Numbers: 2000037337; R01HD111436 (U.S. NIH Grant/Contract: NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be made available to other researchers at the conclusion of this study and after publication of its findings. Data will be uploaded to dbGaP with individual-level data for genotypes and phenotypes collected in this study.
• IPD Sharing Time Frame: De-identified data will be uploaded to dbGaP within one year of completion of the study and will be available indefinitely
• IPD Sharing Access Criteria: Per dbGaP requirements
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No