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.

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 back-up 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.