An exploratory analysis on the influence of genetic variants on weight gain among etonogestrel contraceptive implant users.

OBJECTIVE: To identify genetic variants associated with weight gain related to etonogestrel contraceptive implant use. STUDY DESIGN: We conducted a retrospective analysis from a parent pharmacogenomic study of healthy, reproductive-aged women using etonogestrel implants. We reviewed medical records to calculate objective weight changes from implant insertion to study enrollment and asked participants about subjective weight gain (yes/no) during contraceptive implant use. We used genotyping data (99 genetic variants) from the parent study to conduct backward-stepwise generalized linear modeling to identify genetic variants associated with objective weight changes. RESULTS: Among 276 ethnically diverse participants, median body-mass index (BMI) was 25.8 kg/m2 (range 18.5-48.1). We found a median weight change of +3.2 kg (range -27.6 to +26.5) from implant insertion to study enrollment. Report of subjective weight gain had minimal agreement with measured weight gain during implant use (Cohen's kappa = 0.21). Our final generalized linear model contained two variables associated with objective weight change that met conservative statistical significance (p < 5.0 × 10-4). Participants with two copies (homozygous) of the ESR1 rs9340799 variant on average gained 14.1 kg more than all other participants (p = 1.4 × 10-4). Higher enrollment BMI was also associated with objective weight gain (ß = 0.54, p = 9.4 × 10-12). CONCLUSION: Genetic variants in the estrogen receptor 1 (ESR1) do not have known associations with obesity or metabolic syndrome, but there is physiologic plausibility for a progestin-mediated genetic association between ESR1 and weight gain. Additional genetic research is needed to substantiate our findings and elucidate further advances in individualized counseling on the risk of weight gain with exogenous steroid hormones. IMPLICATIONS: Genetic variation in the estrogen receptor 1 gene may account for variability in weight gain among etonogestrel contraceptive implant users. If these findings can be replicated with other progestin-containing medications, we may be able to better individualize contraceptive counseling.

Pre- and post-operative counseling for women on hormonal contraceptives receiving sugammadex at an academic hospital.

Sugammadex is a steroid binder and can potentially bind the estrogens and progestins contained within hormonal contraception. Therefore, the FDA label for sugammadex contains a drug-drug interaction warning between this medication and hormonal contraception, advising that women taking hormonal contraception use a backup contraceptive method or abstinence for seven days after exposure to sugammadex. However, given concerns that this warning may not be appropriately provided to at-risk patients, we conducted a retrospective chart review to identify women administered sugammadex while using hormonal contraception to identify documented counseling on this drug-drug interaction prior to implementation of a formalized counseling process. We reviewed 1000 randomly selected charts from the University of Colorado Hospital between January 2016 and December 2017. We identified 134 women using hormonal contraception at the time of sugammadex exposure; only one patient (0.7%, 95% CI 0.0, 4.1) had documented counseling. One patient had an unintended pregnancy within the same cycle as her exposure to sugammadex. Improved counseling processes are needed to avoid unnecessary risk for unintended pregnancies.

Relationship Between Etonogestrel Concentrations and Bleeding Patterns in Contraceptive Implant Users.

OBJECTIVE: To estimate whether serum etonogestrel concentrations influence bleeding patterns and related side effects in contraceptive implant users. METHODS: We conducted a prospective cross-sectional study with healthy, reproductive-aged women using etonogestrel implants for 12-36 months. Participants completed a brief questionnaire to assess their current bleeding pattern and any experience of abnormal bleeding with the implant. We then measured serum etonogestrel concentrations. We also reviewed the charts of participants to determine whether a prescription for oral contraceptive pills was ever given for treatment of implant-related bothersome bleeding. We performed multivariable logistic regression to test for associations between serum etonogestrel concentrations and both bleeding patterns and related side effects. RESULTS: We enrolled 350 women, and 59.4% reported having experienced abnormal bleeding with the contraceptive implant. Only 14.9% of participants reported amenorrhea and 37.7% reported monthly periods. Among participants with reviewable medical records (n=253), roughly 20% had received a prescription for oral contraceptive pills during implant use. Increasing serum etonogestrel concentrations were significantly associated with increasing odds of reporting abnormal bleeding (adjusted odds ratio [aOR] 1.005, P=.015) and increasing odds of having received an oral contraceptive pill prescription (aOR 1.008, P=.002). For every 100 pg/mL increase in serum etonogestrel concentration, contraceptive implant users in this study had 1.6 times the odds of reporting abnormal bleeding and 2.3 times the odds of having received a prescription as treatment for bothersome bleeding. CONCLUSION: We found both objective and subjective evidence that higher levels of progestin from the contraceptive implant were associated with bleeding side effects experienced by women in this study. Pharmacologic variation may influence the side effects women experience with a variety of hormonal contraceptive methods, in turn affecting patient satisfaction and discontinuation rates.