# Influence of genetic variants on steroid hormone metabolism and progestin-related side effects in contraceptive implant users

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2022 · $77,750

## Abstract

PROJECT SUMMARY
Steroid hormones are some of the most commonly prescribed medications, yet little is known about the
determinants of their disposition, response, and toxicity. Pharmacogenomics is the study of the relationship
between genetic variations and interindividual variability in drug efficacy, metabolism, and safety. The results of
pharmacogenomic investigations have led to the Clinical Pharmacogenetics Implementation Consortium
developing actionable clinical guidelines for over 35 drug-gene pairs. Despite rapid progress in
pharmacogenomics for many areas of medicine, there is scant information about genetic determinants of
steroid hormone (i.e. estrogens and progestins) efficacy, metabolism, and safety. Steroid hormones are used
throughout a woman's life-span for a multitude of indications including contraception, preterm birth prevention,
hormone replacement therapy, and many others. Given the high prescription rate of steroid hormone
medications, it is imperative that we understand the relationship between individual genetic variation and these
medications. We aim to identify novel areas of the human genome that are associated with steroid hormone
metabolism and associated with clinically relevant side effects. We plan to use etonogestrel contraceptive
implant users for this study given the steady-release pharmacology of the contraceptive implant and its
independence from issues of protocol adherence. We also have preliminary data from a candidate gene study
of etonogestrel implant users, which demonstrated associations between genetic variants and both serum
etonogestrel concentrations and progestin related side effects. However, the majority of pharmacologic
variability remains unaccounted for and our candidate gene approach could not include all genetic regions
pertinent to steroid hormone metabolism and function. We plan to enrich our existing biobank of genomic
samples from 339 contraceptive implant users with another 561 using a contraceptive implant during its
steady-state period of 12-36 months of use to create a discovery cohort of 700 implant users and a replication
cohort of the remaining 200 women. We have currently enrolled 101 new participants and require 460
additional participants to meet our planned sample size. We will then perform a Genome Wide Association
Study with our discovery cohort and examine for associations with serum etonogestrel concentrations that are
indicative of possible increased or decreased metabolism. All participants will also complete a questionnaire to
gather pertinent lifestyle factors and side-effect data that we will analyze for associations with our genomic
results. We will utilize our replication cohort to duplicate associations for up to five single nucleotide
polymorphisms with the strongest associations identified in the discovery cohort. This study will identify novel
genetic targets that can directly inform future research endeavors and contribute data to the eventual creation
of preci...

## Key facts

- **NIH application ID:** 10356154
- **Project number:** 5R03HD101551-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Aaron Lazorwitz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,750
- **Award type:** 5
- **Project period:** 2021-02-18 → 2024-02-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356154

## Citation

> US National Institutes of Health, RePORTER application 10356154, Influence of genetic variants on steroid hormone metabolism and progestin-related side effects in contraceptive implant users (5R03HD101551-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10356154. Licensed CC0.

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