Genetic variance and hormonal contraceptive effectiveness

Article

A new study aimed to better understand why birth control may fail for some women by looking at genetic variants.

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As the popularity of hormonal contraception continues to rise, there is an urgency to better understand to role of genetic variants on their serum concentrations, efficacy, and toxicity. A recent study in Obstetrics & Gynecology looked at how genetic variants might influence steady-state etonogestrel concentrations in contraceptive implant users. 

The study enrolled women between ages 18 and 45 who had been using etonogestrel implants for 12 to 36 months without concomitant use of hepatic enzyme inducers or inhibiters. Data on participant characteristics, including body mass index (BMI), were gathered along with two blood samples collected at a single time point. One blood sample was for serum etonogestrel concentration analysis and the other was for DNA extraction. 

The authors assessed 120 single nucleotide polymorphisms in 14 genes reported to be involved in metabolism, regulation, and function of estrogens and progestins. Generalized linear modeling was used to identify genetic variants associated with steady-state etonogestrel concentrations. 

The median serum etonogestrel concentration of the 350 women enrolled in the study was 137.4 pg/mL (range 55.8 – 695.1). Based on their linear modeling, the authors identified three genetic variants associated with serum etonogestrel concentration: NR1I2(PXR)rs2461817 (ß = 13.36, P= .005), PGR rs537681 (ß = -29.7, P= .007), and CYP3A7*1C(ß = -35.06, P= .025). The variant allele frequencies were 69.4%, 84.9% and 5.1%, respectively. In addition to the three genes, the linear model also identified two nongenetic factors associated with etonogestrel concentrations: higher BMI and duration of implant use. 

The authors believe their findings help illustrate why birth control may fail for some women. As more genetic data become available, ob/gyns should consider adding genetic screening and tailoring treatments to individual patients who express interest in hormonal contraception.

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