Objective Abnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions. Study design Female non-pregnant Sprague–Dawley rats ( N ?=?22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20?μg/kg/day) and 4) with high T4 doses (100?μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in?vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect. Results Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (?17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (?51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Conclusion Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients. Highlights ? Hypothyroidism decreased duration while increasing the frequency of contractile activity. ? T4-treatment induces a dose-dependent increase in the duration of contractions. ? However, this treatment decreases the frequency of the contractile events. ? Abnormal uterine contractile pattern are induced by T4-treatment.
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机译：目的最近在接受左甲状腺素（T4）治疗的孕妇的子宫条中证实了子宫收缩异常。这些异常与剖腹产和相关手术并发症的风险增加有关。迄今为止，尚无研究调查甲状腺功能减退或T4治疗可改善子宫收缩力。本文中，我们分析了T4对子宫收缩的生理作用。研究设计使用雌性非妊娠Sprague-Dawley大鼠（N = 22）分为四组：1）对照，2）甲状腺功能减退，3）低T4剂量（20？μg/ kg /天）治疗甲状腺功能减退4）高T4剂量（100？μg/ kg /天）。甲状腺功能低下症是由碘缺乏饮食引起的。等距张力测量是在离体器官浴中对子宫肌层组织进行的。使用药理学工具评估收缩活动参数（幅度，持续时间，频率和曲线下面积）以评估其效果。结果筛查甲状腺功能证实了所有大鼠在无碘饮食下的甲状腺功能减退状态，随后给予T4平衡甲状腺功能减退症。结果表明，甲状腺功能减退显着减少了收缩持续时间（约17％）和增加了收缩频率（+ 26％），而高剂量的T4增加了持续时间（+ 200％）和降低了频率（约51％）。因此，这些结果模拟了先前在接受T4治疗的甲状腺功能减退孕妇的子宫组织中观察到的异常收缩模式。结论我们的数据表明，T4处理可引起肌层反应性的改变。因此，结合我们先前对人类子宫肌条的观察，应改善甲状腺功能减退症的治疗，以降低该组患者的剖宫产率。强调 ？甲状腺功能减退症减少持续时间，同时增加收缩活动的频率。 ？ T4处理可引起收缩持续时间的剂量依赖性增加。 ？但是，这种治疗降低了收缩事件的频率。 ？ T4治疗可引起子宫收缩异常。
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