scholarly journals Effects of the Selective Progesterone Receptor Modulator Asoprisnil on Uterine Artery Blood Flow, Ovarian Activity, and Clinical Symptoms in Patients with Uterine Leiomyomata Scheduled for Hysterectomy

2008 ◽  
Vol 93 (12) ◽  
pp. 4664-4671 ◽  
Author(s):  
Julia Wilkens ◽  
Kristof Chwalisz ◽  
Cong Han ◽  
Jane Walker ◽  
Iain T. Cameron ◽  
...  

Introduction: Asoprisnil, a novel orally active selective progesterone receptor modulator, is being studied for the management of symptomatic uterine leiomyomata. The exact mechanism of action is not yet discerned. The primary objectives of this double-blind, randomized, placebo-controlled study included evaluation of the effect of asoprisnil on uterine artery blood flow. Furthermore, we assessed effects of asoprisnil on leiomyoma symptoms. Patients and Methods: Thirty-three premenopausal patients scheduled for hysterectomy due to symptomatic uterine leiomyomata were recruited in four centers and treated with 10 or 25 mg asoprisnil or placebo for 12 wk before surgery. At baseline and before hysterectomy, all patients underwent sonographic assessment to measure impedance to uterine artery blood flow, determined by resistance index and pulsatility index, as well as volumes of largest leiomyoma and uterus. In addition, patients recorded intensity and frequency of menstrual bleeding on a menstrual pictogram. Each asoprisnil treatment was compared with placebo. Results: The increased pulsatility index in both asoprisnil groups and the statistically significantly increased resistance index within the 25-mg asoprisnil group suggest a moderately decreased uterine artery blood flow. Analysis of menstrual pictogram scores showed a statistically significant larger decrease in frequency and intensity of bleeding for both asoprisnil groups compared with placebo. Bleeding was suppressed by asoprisnil 25mg in 91% of patients. Asoprisnil treatment was well tolerated when administered daily for a 12-wk period, and no serious adverse events occurred. Conclusion: Asoprisnil moderately reduced uterine artery blood flow. This effect may contribute in part to the clinical effects of asoprisnil.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 137-138
Author(s):  
Allison M Meyer ◽  
Natalie B Duncan ◽  
Katy S Stoecklein ◽  
Emma L Stephenson

Abstract To determine parity effects on late gestational uteroplacental blood flow, uterine artery hemodynamics were measured in 13 primiparous and 11 multiparous (parity 3 and 4) non-lactating, fall-calving crossbred females beginning 109 d prepartum. Females were nutritionally managed as one group to meet or exceed nutrient requirements. Transrectal color Doppler ultrasonography of the both uterine arteries was conducted 3 to 6 times per female across late gestation, ending at approximately 20 d prepartum. Data were analyzed with parity (primiparous vs. multiparous), day prior to calving, and their interaction in the model; day was a repeated effect. Dam BW was greater (P < 0.001) for multiparous than primiparous females, and increased (P = 0.004) as gestation progressed. Calf birth weight was unaffected (P = 0.87) by parity. The parity x day interaction tended to affect (P = 0.06) ipsilateral uterine artery blood flow (L/min), where multiparous cows had a greater increase per day. Total and contralateral uterine artery blood flow were unaffected (P ≥ 0.11) by parity, but increased (P < 0.001) with day of gestation. When expressed relative to dam BW, total and contralateral blood flow were greater (P ≤ 0.04) in primiparous than multiparous females; ipsilateral blood flow was unaffected (P ≥ 0.13) by parity, however. Ipsilateral pulsatility index and both resistance indices were unaffected (P ≥ 0.28) by parity and day, but day tended to affect (P = 0.07) contralateral pulsatility index. Parity did not affect (P ≥ 0.11) cross-sectional area, mean velocity, peak systolic velocity, and end diastolic velocity of either uterine artery, but all increased (P < 0.001) as gestation progressed. Heart rate was greater (P = 0.03) in primiparous than multiparous females. Data suggest that uterine artery blood flow and heart rate may be altered in primiparous females, even when birth weight is unaffected by parity.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed A ElKady ◽  
Noha H Rabie ◽  
Mohammed H Mostafa ◽  
Amany M Hafez

Abstract Background Preeclampsia is pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation. Aim of the Work to assess the effect of injecting magnesium sulfate on Doppler parameters of uterine artery, umbilical and fetal middle cerebral arteries (MCA) in women with severe preeclampsia. Patients and Methods This study included eighty pregnant with severe preeclampsia or eclampsia who were given magnesium sulphate therapy in Ain Shams University Maternity hospital. The Study group included 80 pregnant patients Doppler flow velocity parameters (resistance index [RI], pulsatility index [PI] and systolic/diastolic [S/D] ratio) were evaluated in the uterine, fetal umbilical and middle cerebral arteries before and 20 minutes after intravenous administration of 6 grams of magnesium sulfate (Loading dose). Results Magnesium sulfate had significant hemodynamic effects with significant reduction of systolic and diastolic blood pressure. Regarding the Doppler studies, it was found that after administration of magnesium sulfate there was significant reduction in the Doppler velocimetry parameters (Resistance index[RI], Pulsatility index[PI] and systolic/diastolic[S/D] ratio) in the uterine, umbilical and fetal middle cerebral arteries denoting decreased vascular resistance with increased blood flow in these vessels. Conclusion Intravenous administration of magnesium sulfate in pregnant women with severe preeclampsia and eclampsia resulted in a decrease in uterine artery, fetal umbilical and middle cerebral arteries Doppler indices with reduced resistance to blood flow in these vessels.


2017 ◽  
Vol 35 (05) ◽  
pp. 521-526 ◽  
Author(s):  
Ira Bernstein ◽  
Joan Skelly ◽  
Sarah Heil ◽  
Stephen Higgins ◽  
Kylie Cooper

Objective This study aims to evaluate the relationship of maternal smoking to uterine artery hemodynamics and examine independent contributions to birth weight and fetal body composition. Study Design Women were enrolled in a prospective randomized controlled study targeting smoking abstinence. Uterine artery Doppler ultrasound was performed and volumetric blood flow was calculated. Third trimester ultrasound estimates of fetal body composition were performed and birth weight was recorded. Results Uterine artery volumetric flow and resistance index (RI) were significantly correlated with birth weight adjusted for gestational age (R = 0.35, p = 0.002; R = − 0.27, p = 0.02). Volumetric flow was significantly associated with fetal fat mass (R = 0.30, p = 0.018). Smoking status did not have significant effects on lean body mass (t [61] = 0.60, p = 0.55), fat mass (t [61] = 1.67, p = 0.10), or volumetric flow (t = 0.86, df = 87, p = 0.39). Stepwise regression identified volumetric flow (β = 0.81, 95% confidence interval [CI]: 0.35–1.27, p < 0.001), maternal prepregnancy body mass index (β = 16.04, 95% CI: 2.57–29.50, p = 0.02), and fetal sex (β = 346.28, 95% CI: −532.64 to 159.91, p < 0.001, where male = 0 and female = 1) as independent contributors to birth weight adjusted for gestational age. Conclusion No direct relationship of smoking to uterine artery hemodynamics was demonstrated. Volumetric flow was an independent contributor to birth weight and was associated with fetal fat deposition, while smoking was not independently associated with either outcome.


2006 ◽  
Vol 28 (4) ◽  
pp. 569-569
Author(s):  
S. Boito ◽  
S. Rigano ◽  
G. Pennati ◽  
L. Mandia ◽  
A. Padoan ◽  
...  

Author(s):  
Jay S Mishra ◽  
Sathish Kumar

Abstract Preeclampsia is a pregnancy-related hypertensive disorder with unclear mechanisms. While hypersensitivity to angiotensin II via vasoconstrictive angiotensin type-1 receptor (AT1R) is observed in preeclampsia, the importance of vasodilatory angiotensin type-2 receptor (AT2R) in the control of vascular dysfunction is less clear. We assessed whether AT1R, AT2R and eNOS expression is altered in placental vessels of preeclamptic women and tested if ex vivo incubation with AT2R agonist Compound 21 (C21; 1 μM) could restore AT1R, AT2R and eNOS balance. Further, using a rat model of gestational hypertension induced by elevated testosterone, we examined whether C21 (1 μg·kg−1·day−1, oral) could preserve AT1R and AT2R balance and improve blood pressure, uterine artery blood flow, and vascular function. Western blots revealed that AT1R protein level was higher while AT2R and eNOS protein were reduced in preeclamptic placental vessels, and AT2R agonist C21 decreased AT1R and increased AT2R and eNOS protein levels in preeclamptic vessels. In testosterone-dams, blood pressure was higher, and uterine artery blood flow was reduced, and C21 treatment reversed these levels similar to those in controls dams. C21 attenuated the exaggerated Ang II contraction and improved endothelium-dependent vasorelaxation in uterine arteries of testosterone-dams. These C21-mediated vascular effects were associated with decreased AT1R and increased AT2R and eNOS protein levels. C21 also increased serum nitrate/nitrite and bradykinin production in testosterone-dams and attenuated the feto-placental growth restriction. Thus, AT1R upregulation and AT2R downregulation is observed in preeclampsia and testosterone-model, and increasing AT2R activity could help restore AT1R and AT2R balance and improve gestational vascular function.


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