The pharmacogenomics of contraception: genetic determinants of etonogestrel pharmacokinetics
Contraception
Awarded 2017
Complex Family Planning Fellowship Research
Aaron Lazorwitz, MD
University of Colorado
$99,922

Pharmacogenomics is the study of how individual genetic differences affect drug metabolism, efficacy, and side effects. Women using the exact same contraceptive method for the same period of time have wide variability in both serum drug levels and side effect profiles from their contraception. This pharmacogenomic study aimed to help us better understand how individual genetic differences affect both the serum drug levels and side effect profiles in women using the same contraceptive method.
We performed a candidate gene study where we chose 120 unique variants in genes involved in steroid hormone (e.g. progestins and estrogens) metabolism, regulation, and function. We enrolled 350 reproductive age women who had an etonogestrel contraceptive implant in place between 12 and 36 months. We measured the amount of drug (etonogestrel) in each woman’s serum and genotyped them for the 120 genetic variants selected. We found body-mass index, duration of implant use, and three genetic variants that were associated with serum drug levels.
One of the significant genetic variants, CYP3A7*1C, was associated with lower drug levels. This variant causes adults to create an enzyme (CYP3A7) normally only produced by fetuses that can break down steroid hormones, like etonogestrel. Thus, women with the CYP3A7*1C variant have increased metabolism of hormone medications and could be at higher risk of decreased efficacy. We also found that suspected high-yield genetic variants that should have changed drug levels in implant users did not have any effect. These findings demonstrate that more research is needed to find new areas of the human genome that can help us further explain this variability in hormone drug levels.

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