Department of Health and Kinesiology, Texas A&M University, College Station, TX, USA.
Department of Obstetrics & Gynecology, University of Saskatchewan, Saskatoon, SK, Canada.
Reprod Biol Endocrinol. 2021 Mar 22;19(1):47. doi: 10.1186/s12958-021-00729-w.
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. 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.
Intact, 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.
Prior 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.
Assessment 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.
长效、可逆避孕方法（LARC；仅孕激素）是一种越来越常见的生殖年龄妇女选择的激素避孕方法，旨在抑制卵巢功能和月经周期性。总体目标是开发和验证一种植入依托孕烯（ENG）LARC 的啮齿动物模型，其剂量相当于女性在前 3 年 ENG 皮下棒 LARC 使用期间每个剂量的等效剂量。
将 16 周龄的完整、处女、雌性 Sprague-Dawley 大鼠随机分为 4 组（每组 8 只）的 ENG LARC（高 0.30μg/d、中 0.17μg/d、低 0.09μg/d、安慰剂 0.00μg/d），通过皮下植入缓释微球。在植入微球前和植入后 21 天，通过阴道涂片、超声生物显微镜（UBM）、隐静脉血样采集、食物消耗和体重对动物进行监测。数据采用卡方检验、非参数、单变量和重复测量 2 因素方差分析进行分析。
在植入微球之前，治疗组之间发情周期阶段的时间没有差异（p>0.30）。植入微球后，发情和发情时间呈剂量依赖性（p<0.05），高剂量组发情时间延长，发情时间缩短。在插入微球之前，治疗组与发情周期分类之间没有关联（p=0.57），但在植入微球后，与发情周期分类呈剂量依赖性关联（p<0.02）。UBM（卵巢体积、卵泡计数、黄体计数）的测量值表明，植入微球后卵巢功能发生了改变。
发情周期性评估表明，在更多的无周期性大鼠和更长的发情期持续时间方面存在剂量反应关系。因此，该模型中的每个剂量都模拟了一些在使用 ENG LARC 的女性卵巢中观察到的变化，并为未来研究对非生殖组织的影响提供了机会。
