Abstract
BackgroundLong-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use.MethodsIntact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA.ResultsPrior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation.ConclusionAssessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.
Highlights
Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity
Subdermal rod and intrauterine device (IUD) LARC modalities provide multiple advantages to women, including a high efficacy independent of patient compliance, long term unattended use (3 or more years), highly effective ovarian and menstrual suppression [10] and reduced risk for venous thromboembolism and breast cancer compared with combined oral contraception use [11]
For subdermal rod and IUD LARC modalities the secretion of progestin decreases slowly over time [12], while remaining well above the contraceptive efficacy threshold
Summary
Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. Hormonal contraception (HC) is routinely used by reproductive age women (18–49 years old) to suppress ovarian function and menstrual cycling. Subdermal rod and IUD LARC modalities provide multiple advantages to women, including a high efficacy independent of patient compliance, long term unattended use (3 or more years), highly effective ovarian and menstrual suppression [10] and reduced risk for venous thromboembolism and breast cancer compared with combined oral contraception use [11]. For subdermal rod and IUD LARC modalities the secretion of progestin decreases slowly over time [12], while remaining well above the contraceptive efficacy threshold. Adequate estrogen exposure is important in neurological, cardiovascular, and musculoskeletal protection, atrial vasodilation, healthy immunity and liver protein function, as well as breast and endometrial tissue health [14, 15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
