Perfusion In Women Research Articles

Scientific Rationale and Design of a Phase I Safety Study of Relaxin in Women with Severe Preeclampsia

The pathophysiology of preeclampsia involves profound systemic vasoconstriction. Its etiology may be related to reduced blood flow to the placenta, leading to the elaboration of soluble, vasoactive factors which increase maternal systemic vascular resistance and cause renal dysfunction. Reduced bioactivity of vascular endothelial growth factor (VEGF) may play a central role in this pathophysiology. Previous clinical studies have strongly suggested that relaxin is a systemic and renal vasodilator. In nonclinical studies, relaxin administration to monkeys has been associated with increased vessel density in the endometrium, and in previous human trials relaxin administration has been highly correlated with increased menstrual bleeding in women. VEGF has been proposed as a mechanism for these endometrial effects. Together, these data suggest that relaxin may be able to relieve systemic and renal vasoconstriction and improve placental perfusion in women with preeclampsia. As a first step in the development program for relaxin in this indication, a multicenter, randomized, double-blind, placebo-controlled phase I safety study in women with severe preeclampsia has been launched in the USA. Three doses of relaxin, 3, 10, and 30 microg/kg of body weight/day, or placebo, will be administered for up to 72 h in women admitted to the hospital for management of their disease. Although the trial is primarily focused on safety, signs of efficacy, such as changes in blood pressure and renal markers, will also be assessed.

Optical properties of the breast during spontaneous and birth control pill-mediated menstrual cycles

Mastodynia is correlated with the menstrual cycle. Using frequency-domain near-infrared spectroscopy (FD-NIRS), we investigated changes in breast perfusion in women who were or were not using hormonal contraception. Healthy volunteers, on or not on hormonal contraception, were examined. Optical properties were measured in all quadrants of both breasts, and physiological parameters were calculated. Measurements were repeated every other day during one complete menstrual cycle. Measurements were comparable in all quadrants. Data remained unchanged during the entire cycle in patients using hormonal contraception. However, a biphasic variation of deoxyhemoglobin, oxyhemoglobin, total hemoglobin (tHb), and water content (H(2)O) was observed in women not using contraception. tHb and H(2)O distinctly increased during the ovulation period and remained elevated throughout the luteal phase. It was concluded that FD-NIRS allows accurate measurement of optical properties of human breasts. As opposed to the menstrual cycles of persons using oral contraception, spontaneous menstrual cycles exhibit biphasic variations of tissue perfusion parameters. These findings are important for the investigation of mastodynia.

Prognostic value of poststress left ventricular volume and ejection fraction by gated myocardial perfusion SPECT in women and men: Gender-related differences in normal limits and outcomes

Whether there are gender differences in the prognostic application of gated myocardial perfusion single photon emission computed tomography (SPECT) has not been assessed. Gender-specific normal limits of poststress volume and ejection fraction (EF) were obtained in 597 women and 824 men with a low likelihood of coronary artery disease and normal perfusion and were applied in a prognostic evaluation of 6713 patients (2735 women and 3978 men). Patients underwent rest thallium-201/stress technetium-99m sestamibi gated myocardial perfusion SPECT and were followed up for 35 +/- 14 months. The upper limit of the end-systolic volume (ESV) index was 27 mL/m2 in women and 39 mL/m2 in men, and the upper limit of the end-diastolic volume index was 60 mL/m2 in women and 75 mL/m2 in men. The lower limit of the EF was 51% in women and 43% in men. Gated SPECT variables provided incremental prognostic information in both genders. Women with severe ischemia and an EF lower than 51% or an ESV index greater than 27 mL/m2 were at very high risk of cardiac death or myocardial infarction (3-year event rates of 39.8% and 35.1%, respectively), whereas women with severe ischemia but an EF of 51% or greater or an ESV index of 27 mL/m2 or less were at intermediate or high risk (3-year event rates of 10.8% and 15.2%, respectively). Poststress EF and ESV index by gated myocardial perfusion SPECT provide comparable incremental prognostic information over perfusion in women and men. After separate criteria for abnormal EF and ESV index in women are used, the combination of severe ischemia and abnormal EF or ESV index identifies women at very high risk of cardiac events.

Increased Plasma Adrenomedullin in Women With Recurrent Pregnancy Loss

In Brief OBJECTIVE To evaluate vascular changes and uterine perfusion in women with recurrent pregnancy loss. METHODS We measured plasma levels of adrenomedullin of 100 pregnant women in the midluteal phase of a nonpregnant cycle (control group: n = 62; recurrent pregnancy loss group: n = 38). We measured the pulsatility index (PI) in the uterine arteries by transvaginal pulsed Doppler ultrasonography at the same time. RESULTS The plasma level of adrenomedullin in women with recurrent pregnancy loss (5.6 ± 1.9, mean ± standard deviation) was significantly higher (P > .001) than that in control women (3.6 ± 1.7). Uterine arterial PI of women with recurrent pregnancy loss (2.70 ± 0.47) was significantly higher (P > .001) than that in control women (2.09 ± 0.39). Plasma level of adrenomedullin had a significant positive correlation with uterine arterial PI both in the control group (r = .58, P < .001) and in the recurrent pregnancy loss group (r = .78, P < .001). Both plasma adrenomedullin concentration (7.2 ± 2.3) and uterine arterial PI (3.06 ± 0.36) were significantly high in women with antiphospholipid antibodies. CONCLUSION Plasma adrenomedullin may serve as a useful biochemical marker for recurrent pregnancy loss caused by impaired uterine perfusion. The plasma level of adrenomedull in in women with recurrent pregnancy loss is significantly higher than that in control women.

Increased plasma adrenomedullin in women with recurrent pregnancy loss.

To evaluate vascular changes and uterine perfusion in women with recurrent pregnancy loss. We measured plasma levels of adrenomedullin of 100 pregnant women in the midluteal phase of a nonpregnant cycle (control group: n = 62; recurrent pregnancy loss group: n = 38). We measured the pulsatility index (PI) in the uterine arteries by transvaginal pulsed Doppler ultrasonography at the same time. The plasma level of adrenomedullin in women with recurrent pregnancy loss (5.6 +/- 1.9, mean +/- standard deviation) was significantly higher (P >.001) than that in control women (3.6 +/- 1.7). Uterine arterial PI of women with recurrent pregnancy loss (2.70 +/- 0.47) was significantly higher (P >.001) than that in control women (2.09 +/- 0.39). Plasma level of adrenomedullin had a significant positive correlation with uterine arterial PI both in the control group (r =.58, P <.001) and in the recurrent pregnancy loss group (r =.78, P <.001). Both plasma adrenomedullin concentration (7.2 +/- 2.3) and uterine arterial PI (3.06 +/- 0.36) were significantly high in women with antiphospholipid antibodies. Plasma adrenomedullin may serve as a useful biochemical marker for recurrent pregnancy loss caused by impaired uterine perfusion.

The antiandrogenic effect of flutamide improves uterine perfusion in women with polycystic ovary syndrome

Objective: To evaluate whether, by blocking androgen action, flutamide can decrease and normalize vascular resistance in the uterine artery in patients with polycystic ovary syndrome (PCOS). Design: Prospective and controlled study. Setting: Endocrinological Centre of the Department of Obstetrics and Gynecology of the University of Cagliari, Italy. Patient(s): Twenty-two patients with PCOS were enrolled in the study and randomly assigned to one of the following two treatments for 3 months: oral administration of flutamide (250 mg twice daily) or placebo. Intervention(s): Doppler flow measurement of the uterine artery and serum hormone concentration determination during the early follicular phase of the menstrual cycle before treatment and during the third month of treatment. Main Outcome Measure(s): Pulsatility index (PI) of the uterine artery before and during treatment. Result(s): The PI of the uterine artery decreased significantly during treatment. No difference was found in patients treated with placebo. Correlation was found only between the PI values of the uterine artery and DHEAS. Conclusion(s): The low uterine perfusion that characterizes patients with PCOS can be improved by the antiandrogenic effect of flutamide.

The antiandrogenic effect of flutamide improves uterine perfusion in women with PCOS.

Objective: To study if the reduction of androgen action induced by flutamide can improve vascular resistance of uterine arteries in patients with polycystic ovary syndrome (PCOS). Design: Prospective and randomized study. Materials/Methods: Twenty-two patients affected by PCOS were enrolled in the study and were randomly assigned to one of the two treatment for three months: oral administration of flutamide (250 twice a day) or placebo. Fifteen women without PCOS were enrolled as control group. All patients were submitted to Doppler flow measurement of uterine artery and serum hormone concentration determination during the early follicular phase. In PCOS-patients the Doppler flow measurements and the hormonal assessments were repeated in the third month of treatment. Results: In PCOS-patients the mean pulsatility index (PI) of uterine artery was significantly higher than that of control group (3.34 ± 0.7 vs 2.11 ± 0.5, p < 0.05). Similarly, in PCOS-patients LH, total Testosterone, free Testosterone and Androstenedione levels and LH/FSH ratio were significantly higher than those of control group (Table 1). In PCOS-patients treated with Flutamide a significantly decrease of PI of uterine artery was observed during treatment (3.48 ± 0.8 vs 2.66 ± 0.4, p < 0.05). No difference was found in patients treated with placebo. As for hormonal features, during treatment with flutamide or placebo non significantly changes in hormone assessment were observed, even if DHEAS showed a non significantly decrease. Correlation was found between PI of uterine artery and DHEAS (r = 0.68, p < 0.03).Table 1Hormonal parameters in patients with PCOS and in the control group.Control groupPCOS groupFlutamidePlaceboBeforeDuringBeforeDuringLH (IU/L)6.27 ± 2.59.14 ± 6.310.23 ± 6.88.86 ± 5.29.14 ± 6.4FSH (IU/L)5.46 ± 1.34.63 ± 1.05.04 ± 1.74.81 ± 1.64.46 ± 2.1LH/FSH1.16 ± 0.72.33 ± 1.52.26 ± 1.42.14 ± 0.92.37 ± 1.3E2 (pg/mL)25.8 ± 20.327.14 ± 23.118.28 ± 14.630.81 ± 27.326.87 ± 22.6PRL (ng/mL)12.7 ± 9.711.5 ± 7.515.9 ± 8.114.1 ± 6.312.8 ± 7.4t Testosterone (ng/mL)0.56 ± 0.10.73 ± 0.20.69 ± 0.30.74 ± 0.20.68 ± 0.1f Testosterone (pg/mL)1.48 ± 1.12.81 ± 1.22.76 ± 1.42.90 ± 1.32.79 ± 1.5DHEAS (ug/mL)1.35 ± 0.41.99 ± 1.50.99 ± 0.412.16 ± 1.41.85 ± 1.517-OHP (ng/mL)0.87 ± 0.21.22 ± 0.31.24 ± 0.91.19 ± 0.21.31 ± 0.6A (ng/mL)2.0 ± 0.62.96 ± 1.122.24 ± 1.163.05 ± 1.213.14 ± 1.6 Open table in a new tab Conclusions: The present study seems to suggest that androgens are the most important cause of the high resistance observed in uterine arteries of patients affected by PCOS. In fact, the low uterine perfusion that characterizes these patients is improved by the antiandrogenic effect of flutamide.

F27A correlation of the uterine and ovarian perfusion with parity of women having a history of recurrent spontaneous abortions

BackgroundTo explore a relationship between the incidence of recurrent spontaneous abortions (RSA) and values of Doppler indices characterizing the uterine and ovarian perfusion in women with history of Primary and secondary RSA.MethodA prospective study was carried out in which color Doppler transvaginal ultrasonography was used to estimate the endometrial thickness (ETH), the uterine pulsatility index (UTAP) and the intraovarian arterial resistance index (IOARI) on the 21st day of a regular 28‐day menstrual cycle in a control group of 19 healthy fertile nonpregnant parous women and 81 cases of nonpregnant women having a history of RSA.ResultsA highly significant difference (P &lt; 0.001) was observed between UTAPI and IOARI values of control group and women with primary RSA. The same results were obtained for secondary RSA women who had some more 3 abortions. No difference was found for ETH values in control and study groups.ConclusionOur study has demonstrated the presence of a significantly decreased uterine and ovarian perfusion in nonpregnant women with primary RSA and secondary RSA if more than 3 abortions occurred. The significance of this result in the management of RSA requires further study. There was no difference between UTAPI and IOARI values in the control group and secondary RSA women with only 3 abortion.

Effect of chronic administration of cabergoline on uterine perfusion in women with polycystic ovary syndrome

Objective: To confirm whether patients with polycystic ovary syndrome (PCOS) have a reduction in uterine perfusion and to verify whether chronic administration of cabergoline can decrease this high vascular resistance. Design: Prospective randomized trial. Setting: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. Patient(s): Thirty patients were enrolled in the study: 20 affected by PCOS and 10 healthy controls. Patients with PCOS were randomly assigned to one of two treatments for 3 months: oral administration of cabergoline (0.5 mg) every week or oral administration of placebo every week. Intervention(s): All patients underwent transvaginal ultrasonography associated with Doppler flow measurement of the uterine artery, and serum hormone concentrations were determined during the early follicular phase. In women with PCOS, Doppler flow measurement and hormonal assessment were repeated in the early follicular phase of the third month of treatment. Main Outcome Measure(s): Pulsatility index of the uterine artery before and during treatment. Result(s): The mean pulsatility index of the uterine artery in patients with PCOS was significantly higher than that of the control group (3.29 ± 0.5 and 2.01 ± 0.2, respectively). Patients with PCOS treated with cabergoline showed a significant increase in uterine perfusion, with a pulsatility index of 3.14 ± 0.6 before and 2.39 ± 0.5 during the treatment. No difference was found in patients with PCOS treated with placebo. Conclusion(s): Patients with PCOS have high resistance in the uterine arteries, but chronic administration of cabergoline can increase uterine perfusion.