SAT-LB039 Development of an Animal Model of Long-acting, Reversible Contraception at Physiologic Equivalent Doses

Abstract

Hormonal contraception is used routinely by premenopausal women to suppress ovarian function and menstrual cyclicity for various reasons. The most commonly chosen hormonal contraceptive types are combined oral contraceptive pills (ethinyl estradiol and a progestin) and long-acting, reversible contraceptives (LARC; progestin only). The overall objective was to develop and validate a rodent model of implanted LARC, using etonogestrel (ENG) doses at physiologic equivalents to the average dose received by women during the first 3 years of LARC use. Intact, virgin, female Sprague-Dawley rats (n=32; 16-wk-old) were randomized to 1 of 4 groups (n=8/group) of ENG LARC use (high-0.30ug/d, medium-0.17ug/d, low-0.09ug/d, placebo-0.00ug/d) via a slow-release pellet inserted under the skin. Animals were monitored for 21 days prior to pellet insertion and 29 days following pellet insertion using vaginal smears, ultrasound biomicroscopy, saphenous blood draws, food consumption, and body weights. At termination, serum and ovarian/uterine weights were collected. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. Weekly average body weight and daily food consumption did not differ among groups across the study (p>0.63). Weekly blood sampling did not reveal differences in serum estradiol among groups across the study (p=0.22). Ovarian volume and number of ovulatory sized follicles, assessed by ultrasound biomicroscopy, did not differ among groups across the study (p>0.071). Ovarian and uterine weights did not differ among groups at termination (p>0.16). The percentage of time spent in diestrus, proestrus, estrus, and metestrus prior to pellet insertion did not differ among groups (p>0.30). Following pellet insertion, the percentage of time spent in proestrus and metestrus did not differ among groups (p>0.08). The medium dose group spent more time in diestrus than the placebo group and the high dose group spent more time in diestrus than the placebo and low dose groups (p<0.05). Low and medium dose groups spent less time in estrus than the placebo group; the high dose group spent less time in estrus than placebo and low dose groups (p<0.05). An association between LARC dose group and estrus cycle classification was not observed prior to pellet insertion (p=0.57). Following pellet insertion, there was an association between LARC dose and estrus cycle classification (p<0.02). Further, the high dose group had a significantly greater proportion of acyclic animals and a smaller proportion of cyclic animals (p<0.05) compared to the placebo group. The every-other-day ultrasound assessment used in this investigation was unable to detect differences in ovarian function. Assessment of estrus cyclicity indicated a dose-response relationship based on the shift to a larger number of acyclic rats and longer in duration of time spent in the diestrus phase. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.