Re-Evaluating the Association Between Hormonal Contraception and Breast Cancer Risk.

This review aims to summarize and assess key studies investigating the relationship between hormonal contraception and breast cancer risk. Approximately two-thirds of breast cancers express the estrogen receptor, and long-term exposure to estrogen is a debated risk factor for breast cancer development. This hypothesis is based on prior studies looking at reproductive risk factors (endogenous estrogen exposure) along with hormone replacement therapy (exogenous hormone exposure). Historically accepted reproductive risk factors include age at menarche, age at first delivery, and parity. Exogenous hormone exposure encompasses both receipt of hormonal contraception and menopausal hormone replacement therapy. This review highlights the reported risks associated with the most common hormonal contraception methods including oral, transdermal, and transvaginal routes. Large observational studies of the past and more recent works are summarized highlighting gaps in knowledge. Several themes emerge: difficulty accounting for well-established risk factors in analyses of epidemiologic studies, challenges determining whether associations between hormonal contraception and breast cancer are due to the exogenous hormones themselves or to increased engagement with the medical system, and discrepancies between statistically significant and clinically significant risk, odds, and hazard ratios. Understanding the strengths and limitations of these studies will help providers in and outside of oncology support women making decisions regarding both cancer risk-reduction and family planning.

Comparison of plasma etonogestrel concentrations sampled from the contralateral-to-implant and ipsilateral-to-implant arms of contraceptive implant users.

OBJECTIVE: To compare plasma etonogestrel concentrations sampled from the contralateral- versus ipsilateral-to-implant arm. STUDY DESIGN: Sub-analysis of a cross-sectional study in Botswana in 33 participants who provided contralateral and ipsilateral blood samples. RESULTS: Plasma etonogestrel concentrations in contralateral and ipsilateral specimens were highly correlated (correlation coefficient = 0.99; p < 0.0001). Bland-Altman analysis of agreement showed that etonogestrel levels were on average 5.9 pg/mL higher (2.1%) in ipsilateral compared to contralateral specimens (95% confidence interval: -4.1, 15.9 pg/mL). CONCLUSIONS: We found no meaningful differences in plasma etonogestrel concentrations between samples taken from the contralateral- versus ipsilateral-to-implant arm. IMPLICATIONS: Our data suggest that etonogestrel plasma concentrations are unlikely to be meaningfully different between samples drawn from the ipsilateral- versus the contralateral-to-implant arms in etonogestrel contraceptive implant users.

Etonogestrel concentrations among contraceptive implant users in Botswana using and not using dolutegravir-based antiretroviral therapy.

OBJECTIVES: To evaluate whether etonogestrel concentrations are reduced to a level that could potentially reduce contraceptive efficacy when the etonogestrel contraceptive implant is used concomitantly with dolutegravir-based antiretroviral therapy (ART). STUDY DESIGN: We conducted a non-randomized, open-label, cross-sectional pharmacokinetic study among women using single-rod etonogestrel contraceptive implants in Botswana. We compared plasma etonogestrel concentrations, sampled at a single time-point between 3 and 12 months from implant insertion, among implant users living with HIV and receiving dolutegravir-based ART with HIV-negative implant users. We also assessed concentrations among implant users living with HIV and receiving efavirenz-based ART. We compared geometric mean etonogestrel concentrations analyzing data from 142 participants: 97 HIV-negative, 30 using dolutegravir, and 15 using efavirenz. RESULTS: The groups were similar. Duration of implant use was between 3 and 12 months (median = 5). Geometric mean etonogestrel plasma concentrations and 90% confidence intervals of the mean were 227.5(212.4-243.8), 289.6(251.8-333.0) and 76.4(63.9-91.4) pg/mL among the HIV-negative, dolutegravir- and efavirenz-based ART groups, respectively. All women in the HIV-negative and dolutegravir-based ART groups had etonogestrel concentrations above 90 pg/mL; 9/15 women (60%) using efavirenz-based ART had concentrations below 90 pg/mL. On average, etonogestrel levels were lower among individuals who had implants inserted for longer durations. CONCLUSIONS: Implant users receiving dolutegravir-based ART had a higher mean etonogestrel concentration compared to HIV-negative women, and none had etonogestrel concentrations below the posited threshold for ovulation suppression. In contrast, women in the efavirenz-group had much lower etonogestrel concentrations. Overall, these data provide evidence that the etonogestrel implant may be effectively combined with dolutegravir-based ART regimens. IMPLICATIONS: The etonogestrel implant remains a highly effective contraceptive option for women living with HIV who use dolutegravir-based ART.