Chronic levothyroxine and acute T₃ treatments enhance the amplitude and time course of uterine contractions in human

Abstract

This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term (n = 28). Spontaneous contractile activities from T4-treated pregnant women (n = 8) were compared with control patients (n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (-55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency (P < 0.05), which partially mimics the results obtained in strips from T4-treated women. Significant modifications of contractile properties were observed in strips from pregnant women treated with levothyroxine, consistent with those observed with the addition of exogenous T3. Clinical practices of modern obstetrics should take into account the effect of thyroid hormones on uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

Increased maternal TSH and decreased maternal FT4 are associated with a higher operative delivery rate in low-risk pregnancies: A prospective cohort study

“…Parija et al have demonstrated that hypothyroidism reduces calcium channel function in uterine tissue of the pregnant rat [ 29 ]. A study from Corriveau et al has found that the amplitude and time course of contractions is enhanced in patients treated with thyroid hormone compared to controls [ 30 ]. This suggests that thyroid function is of direct influence on myometrial contractility.…”

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model

“…The deiodinase type 1 (DIO1) is responsible for the conversion of T4 into its active T3 form. In keeping with a previous study which showed the presence of this isoform in uterine tissues [5] , DIO1 protein was quantified by Western blotting. Using a primary antibody raised against DIO1 (Santa Cruz, CA), an immunoreactive band of 78 kDa was consistently detected in all tested cytosolic samples while a 42 kDa band was detected using β-actin antibody ( Fig.…”

“…Recently, our research group observed dystonic in vitro uterine contractile patterns in uterine strips from pregnant women under T4 treatment for hypothyroidism during the entire course of their pregnancy. Uterine contractions of larger amplitude, longer duration and decreased frequency were observed in hypothyroid women treated with T4 compared to contractile activity in controls [5] . These results hence raise the issue of whether this modified contractile pattern is caused by hypothyroidism or T4 treatment.…”

“…ELISA assays were performed using a standard rat Thyroxine (T4) and T3 ELISA kit according to the manufacturer's protocol (Neobiolab, Cambridge, MA). Western blot analysis was performed exactly as previously described [5] .…”

“…Kreuzberg et al. demonstrated that in atria from patients presenting latent hyperthyroidism, expression levels of L-type Ca 2+ channels were increased more than threefold [7] which may potentially be correlated with the increase in amplitude observed in myometrial contractile activity [5] . Moreover, thyroid hormones have been shown to influence calcium homeostasis and flux responsible for excitation and contractility, with T4 and T3 modulating its pharmacological control and secretion [8] .…”