Correlation of serum estrogen levels with uterine and carotid arteries flow in postmenopausal women on hormone replacement therapy.

OBJECTIVE: To determine the pattern of blood flow in the patients compliant and non-compliant to hormone replacement therapy. METHODS: In the period of 12 months, 106 postmenopausal women were examined by the color and pulsed Doppler ultrasonography of the blood flow through uterine, common, and internal carotid arteries (Resistance Index, RI). The study was retrospective-descriptive. Patients were divided into three groups: (1) 38 patients compliant with hormone replacement therapy and daily using Premarin/Provera, (2) 27 patients non-compliant with the treatment because of discontinuation of the therapy and/or irregular use of medicine, and (3) control group of 41 women who never used hormone replacement therapy. Results were compared with serum estrogen (E2) drawn on the day of the blood flow assessment. RESULTS: Mean E2 serum concentration in the hormone replacement therapy-compliant group was 90.1 pg/mL, 45.5 pg/mL in the non-compliant group, and 26.6 pg/mL in the control group (p<0.01). Serum E2 concentration correlated with the decrease in resistance to blood flow in the uterine artery (p=0.001), but did not in the common carotid (p=0.34) and internal carotid arteries (p=0.66). The compliant group and control group differed in the uterine artery blood flow (RI 0.78 vs. 0.87, respectively). CONCLUSION: Differences in E2 serum concentration between the groups are related to the hormone replacement therapy and the patients' compliance to the therapy. Small peripheral arteries readily respond to the serum E2 levels, whereas large peripheral arteries (common and internal carotid) are too "rigid" to respond to E2-induced vasodilatation.

Color and pulsed Doppler sonography, gray-scale imaging, and serum CA 125 in the assessment of adnexal disease.

OBJECTIVE: To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses. METHODS: Medical records of 109 patients referred with preexisting adnexal lesions were reviewed retrospectively by comparing preoperative ultrasonic data (gray-scale imaging and color and pulsed Doppler findings) with serum CA 125 levels. RESULTS: Eighty-three masses were removed surgically, confirming seven malignancies and 76 benign tumors, and 26 masses were followed; 15 regressed and 11 persisted. Color and pulsed Doppler sonography showed the highest sensitivity, followed by gray-scale imaging, whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors. All three methods had high negative predictive values (96-100%), whereas only serum CA 125 had a positive predictive value greater than 50%. CONCLUSION: Color and pulsed Doppler sonography, which demonstrate a tumor angiogenic activity, are as accurate as gray-scale imaging in the assessment of adnexal lesions. Together with serum CA 125 marker levels, they produce high negative predictive values, providing reassurance that an adnexal mass is benign.

Transvaginal color Doppler determination of the ovarian and uterine blood flow characteristics in polycystic ovary disease.

OBJECTIVE: To determine blood flow characteristics of ovarian and uterine arteries in patients with endocrinologically and clinically confirmed polycystic ovary disease (PCOD) in comparison with blood flow parameters observed in patients with spontaneous ovulatory cycles. DESIGN: Controlled clinical study. SETTING: Patients from Infertility Service in a tertiary care institution. PATIENTS: Forty patients with confirmed PCOD and 50 control patients in various phases of spontaneous menstrual cycles. MAIN OUTCOME MEASURE: Using transvaginal color Doppler sonography to determine ovarian morphology, ovarian blood vessel visualization rates, and ovarian and uterine arteries blood flow parameters (resistance index, pulsatility index, and maximal peak velocity). These parameters were correlated with serum hormone levels. RESULTS: Polycystic ovaries showed typical vascular pattern: increased stromal vascularity, a positive correlation between increased blood velocities and serum LH levels, and a trend toward lower resistance index and pulsatility index values, whereas uterine arteries revealed significantly increased resistance index and pulsatility index values. CONCLUSIONS: The observed specific intraovarian and uterine vascular pattern in PCOD patients may provide additional data for conventional endocrinologic and ultrasonic diagnostic methods for PCOD.

The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity: a prospective study using transvaginal color Doppler sonography.

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography-were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy. We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of uterine vascularity and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.

Transvaginal color and pulsed Doppler sonography of the endometrium: a possible role in reducing the number of dilatation and curettage procedures.

The objectives of the study were to establish color and pulsed Doppler sonographic characteristics of uterine vascularity in postmenopausal patients with pathologic endometrium in order to reduce the number of unnecessary diagnostic dilatation and curettage procedures. The prospective study involved 42 postmenopausal patients who were examined, prior to dilatation and curettage operation, with transvaginal color and pulsed Doppler sonography. Twenty patients had symptoms such as vaginal bleeding or clinically enlarged uterus and 22 postmenopausal women, from our screening group, were asymptomatic. Endometrial thickness (cut-off value of 8 mm), rates of visualization, and the density of uterine, myometrial (peritumoral) and endometrial (intratumoral) vessels were used, along with pulsatility and resistive indices of these vessels, to assess and correlate with endometrium pathology. Endometrial thickness was greater than 8 mm in all cases of endometrial carcinoma (14 of 14 cases), endometrial hyperplasia (eight of eight cases), and one endometrial polyp. In all cases of uterine myoma (nine cases) and in asymptomatic controls (11 subjects) the endometrium thickness was below 8 mm. Percentage of visualization of myometrial and endometrial vessels in cases of endometrial carcinoma was 93% and 43% respectively, which was significantly higher than for cases with benign endometrium (P < 0.05). RI and PI values of these studied vessels of endometrial carcinoma were significantly lower than those for endometrial hyperplasia (P < 0.05). In 80% of cases of endometrial carcinoma, dense vascularity was found in the myometrium (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of color Doppler in diagnosis of endometriomas.

The aim of this study was to characterize the appearance of the vascular pattern of endometriomas in terms of color Doppler and to verify the role of Doppler flow indices in differentiating endometriomas from other pelvic masses. Twenty patients with suspected endometriosis were referred for evaluation and surgical management of adnexal masses and/or infertility problems. Before surgery, transvaginal sonography was performed using an Ultramark 9 (ATL) Ultrasound system. The color Doppler was used for evaluation of the vascular color distribution. Flow parameters (resistance index (RI) and pulsatility index (PI) were obtained using pulsed Doppler. A total of 24 masses were identified in the 20 patients studied. Sixteen masses proved to be endometriomas, with a mean size of 3.5 +/- 0.4 cm. Of confirmed endometriomas, 81% had a regular internal surface and 63% showed the characteristic homogeneous low-level echoes filling the cyst. Eleven of 16 (69%) endometriomas showed flow by color Doppler. The flow was characteristically limited, with few spots of vascular color seen in each mass. Cases that showed dense vascularity with color Doppler proved not to be endometriomas. The mean +/- SE of the RI and PI for the endometriomas were 0.59 +/- 0.02 and 0.95 +/- 0.1, respectively. All endometriomas showed an RI of > 0.5 with a range of 0.5-0.74, while the PI was 0.59-1.59. No significant differences between flow indices for endometriomas and other benign cystic lesions were noted. Scattered vascularity, one feature of adnexal endometriomas, may help to differentiate them from other lesions of dense vascular distribution, such as corpora lutea or ovarian neoplasms.

The characterization of flow signals from tubal and ovarian arteries using intraoperative continuous wave Doppler.

Ovarian vascular Doppler is a promising screening test for early ovarian cancer detection. However, disagreements on flow indices used, flow signal shapes and ovarian vessel localization cause continuing controversy. We aimed at clarifying some of this confusion by directly measuring the adnexal arterial blood flow during laparotomy. A 10-MHz continuous Doppler probe was used to examine adnexal vessels in 24 patients undergoing laparotomy for benign gynecological pathology. Resistance (RI) and pulsatility (PI) indices were calculated for each vessel and the shape of the flow signals was noted. The tubal arteries showed a low-velocity flow pattern with relatively high end-diastolic flow when compared to the ovarian artery signals obtained from the infundibulopelvic ligament.The mean RIs for the tubal artery and ovarian artery in the infundibulopelvic ligament were 0.59 +/- 0.02 and 0.73 +/- 0.02, respectively. The mean PIs for the tubal and ovarian artery in the infundibulopelvic ligament were 1.11 +/- 0.09 and 1.53 +/- 0.1, respectively. The tubal artery showed a significantly lower RI and PI when compared to the ipsilateral ovarian artery at the infundibulopelvic ligament (p < 0.001 and p = 0.002, respectively) and its hilar branches (p = 0.03 for RI and p = 0.03 for PI). We conclude that tubal artery flow signals, which are measured directly for the first time in this study, are characteristic and are distinct from the ovarian artery signals. Tubal artery signals might be erroneously picked up during transvaginal color Doppler sonography of the ovaries, especially in the presence of conditions causing a decreased impedance to blood flow in the pelvis, such as ovarian tumors. Recognizing the flow signal from the tubal artery may help in differentiating ovarian and tubal vessels detected during color Doppler sonography.

Urinary and amniotic epidermal growth factor during normal and abnormal pregnancies. A comparison based upon umbilical Doppler velocimetry.

Fetal growth retardation is associated with abnormal umbilical flow velocity. We have begun a systematic study of growth factors and their relationship to this specific pattern of growth retardation. Using a specific double-antibody epidermal growth factor (EGF) 125I-radioimmunoassay, we studied urinary EGF in normal pregnancy from 5 to 42 weeks of gestation, and amniotic fluid EGF from 18 to 24 weeks. EGF levels increased from early pregnancy until 21-28 weeks, when they declined to a level at term similar to non-pregnant controls and first-trimester pregnancy levels. There was no significant difference in urinary EGF levels between women delivering appropriate-for-gestational-age (AGA) infants, and those delivering small-for-gestational-age infants (SGA). We conclude that the urinary EGF is not different in the SGA pregnancy from normal pregnancy.

Levels of pesticide residues in Egyptian human milk samples and infant dietary intake.

Contamination of human milk with residues of organochlorine pesticides and polychlorinated biphenyls was studied in a series of investigations concerned with the monitoring of these chemicals in Egyptian food. The DDT complex was the most frequently found pesticide, followed by total hexachlorocyclohexane isomers. Heptachlor and its epoxide, dieldrin, hexachlorobenzene, and oxychlordane were also found but less frequently. Estimated dietary intakes (EDIs) of these contaminants by the breast-fed infants were compared to acceptable daily intakes (ADIs). EDIs of DDT complex, lindane (gamma-HCH), heptachlor + heptachlor epoxide, and oxychlordane were below ADIs. Dieldrin EDI exceeded the acceptable daily intake.

Endovaginal sonography for the early diagnosis of intrauterine and ectopic pregnancies.

Endovaginal sonography, together with beta-HCG titre, was used to diagnose ectopic pregnancy in 58 patients. Transabdominal ultrasound failed to conclude this diagnosis. The data from endovaginal sonography revealed the presence of a gestational sac in all 15 patients with normal pregnancies at a beta-HCG level of 1042 mIU/ml. Of the 23 patients with pathological pregnancies only 61% had an intrauterine gestational sac. Only 15% of the 20 patients with ectopic pregnancies showed an increase in beta-HCG greater than 66% in 48 h, while in normal pregnancy, this increase was found in 71% of the patients. The endovaginal findings of the ectopic gestation revealed a complex adnexal mass in 55%, a cystic mass in 30% and fluid in the cul-de-sac in 20%. The diagnostic indices of adnexal and cul-de-sac sonographic findings in the ectopic group further improved specificity and positive predictive accuracy. The detection of ectopic versus intrauterine gestation showed a high sensitivity of 95%, a specificity of 100%, a positive predictability of 100% and a negative predictability of 97%. The data confirm the value and reliability of endovaginal and cul-de-sac sonography, combined with measurement of the beta-HCG level in the early diagnosis of ectopic pregnancy. This combined approach not only makes the differentiation between normal and extrauterine gestation more accurate but also helps to avoid unnecessary diagnostic laparoscopy and hospitalization.

Bromocriptine in polycystic ovarian disease: a controlled clinical trial.

Bromocriptine and placebo were given to a group of 20 polycystic ovarian disease patients on a double-blind, cross-over basis. Patients were studied for three cycles: a baseline cycle without any medication, a placebo-treated cycle, and a bromocriptine-treated cycle with multiple plasma samples taken during the different phases of the menstrual cycle. The clinical response to bromocriptine was compared with that of a placebo for the following hormones: prolactin (PRL), luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, androstenedione, estradiol-17 beta (E2), estrone (E1), and progesterone. Patients were divided into two subgroups: hyperprolactinemic (basal PRL greater than 20 ng/mL) and normoprolactinemic (basal PRL less than 20 ng/mL), and the response of both subgroups to bromocriptine was compared. Prolactin, LH/FSH ratio, testosterone, and E1 showed a significant drop with bromocriptine, whereas E2 significantly increased. Two out of nine amenorrheic polycystic ovarian disease patients menstruated during bromocriptine treatment, and three patients showed evidence of ovulation.

Ovarian follicular fluid beta-endorphin levels in normal and polycystic ovaries.

The possibility of local ovarian production of beta-endorphin prompted us to measure beta-endorphin levels in 19 follicular fluid samples obtained from normal ovaries and compare them with beta-endorphin plasma levels in 19 women with normal ovulation. beta-Endorphin was extracted through Sepharose-treated chromatography columns and assayed with a specific anti-beta-endorphin antibody. Follicular fluid beta-endorphin levels (21.3 +/- 10.8 pg/ml) were significantly higher (p less than 0.01) than the plasma levels (15.5 +/- 3.35 pg/ml). There was no significant correlation between plasma and follicular fluid beta-endorphin concentrations. Follicles greater than 1 cm in size contained more beta-endorphin than follicles less than 1 cm in size (22.7 +/- 3.5 versus 18.7 +/- 4.4 pg/ml, p less than 0.05). Five follicular fluid samples were obtained from polycystic ovaries. The mean beta-endorphin content (45.1 +/- 7.7 pg/ml) in these follicles was significantly higher than that of normal ovaries (p = 0.001). It is concluded that the ovaries produce beta-endorphin and that polycystic ovaries produce more beta-endorphin than normal ovaries.

A controlled clinical trial for the effect of bromocriptine on the adrenal contribution in polycystic ovarian disease.

Adrenal involvement in polycystic ovarian disease was assessed by measuring dehydroepiandrosterone sulphate in 20 polycystic ovarian disease patients. The response of dehydroepiandrosterone sulphate to bromocriptine treatment was compared to that of placebo, both being given for one cycle on a double-blind, cross over basis. The mean basal DHEA-S was above the upper limit of the normal range (6793 nmol/l) in three patients. The mean basal dehydroepiandrosterone sulphate in the polycystic ovarian disease group was significantly higher than the mean of the normal control group (P less than 0.01). Dehydroepiandrosterone sulphate showed a significant drop with bromocriptine as compared to placebo (P less than 0.001) and a significant correlation with prolactin both before (P less than 0.001) and after treatment with bromocriptine (P less than 0.001). These findings support the hypothesis of adrenal involvement in polycystic ovarian disease and prove the significant effect of bromocriptine on the adrenal which might be of therapeutic value.

Correlation of the ultrasonic appearance of the ovaries in polycystic ovarian disease and the clinical, hormonal, and laparoscopic findings.

The ovarian ultrasonic appearance in 20 patients with polycystic ovarian disease was studied and correlated to the clinical, hormonal, and laparoscopic findings. Ultrasound studies showed that both ovaries were enlarged in 15 patients (15.46 +/- 2.5 cm3). Maximum ovarian surface area was 9.75 +/- 3.38 cm2. Three ultrasonic patterns were detected: (1) isoechoic, with no discernible cysts (four patients); (2) hypoechoic, with multiple small cysts of less than 1 cm (11 patients); (3) hypoechoic, with single cyst of greater than 1 cm (five patients). Ultrasonic estimation of ovarian size was superior to clinical assessment and equal to that of laparoscopic examination. Subtle differences existed between the ultrasonic appearance of the ovaries in hyperprolactinemic subgroups of polycystic ovarian disease compared to normoprolactinemic ones. However, no significant relationship was found between the ovarian size and any of the hormones studied. Obesity, amenorrhea, hirsutism, hyperprolactinemia, and elevated testosterone and dehydroepiandrosterone sulfate levels were more common in the group with enlarged ovaries, whereas oligomenorrhea, elevated luteinizing hormone/follicle-stimulating hormone ratio, and elevated androstenedione and estrone levels occurred more frequently in the group with normal-sized ovaries. The value of ultrasound studies in the management of polycystic ovarian disease is emphasized.

Immunoreactive beta-endorphin in human ovaries.

Beta-endorphin (beta-EP) immunostainable cells were demonstrated in human ovarian tissue using a non-cross-reacting anti-beta-EP serum and the avidin-biotin-peroxidase detection technique. In ovaries from ovulating and premenopausal women, beta-EP immunoreactivity was localized in the luteinized cells of theca interna of maturing follicles with almost negligible staining in granulosa cells; cells of primary follicles did not stain. In corpora lutea, luteinized cells in both theca interna and granulosa, layers were equally positive. In postmenopausal ovaries, staining was detectable only in scattered luteinized stromal cells. This is the first report on the presence of immunoreactive beta-EP in human ovaries, in which beta-EP seems to be produced by the same sex cord cells engaged in active steroidogenesis and may be under gonadotropin central regulation. The significance of this finding is discussed.

Menopausal syndrome: plasma levels of beta-endorphin in post-menopausal women measured by a specific radioimmunoassay.

beta-Endorphin (beta-EP) levels were measured in 13 post-menopausal women (7 surgical, 6 physiological) using a new highly specific and accurate radioimmunoassay, and were found to be significantly lower than among 10 normally menstruating controls (48.6 +/- 13.8 pg/ml vs. 70.0 +/- 18 pg/ml, P less than 0.005). beta-EP levels were measured prior to and 5 days after surgery in 3 of the oophorectomized women, and were found to have decreased by an average of 41%. beta-EP levels were measured immediately after hot flashes experienced by 4 of the post-menopausal women during regular clinic visits, and were found to be significantly elevated above baseline levels (P less than 0.02). Our data confirmed the findings of Genazzani et al. [10], a significant lowering of beta-EP at menopause. Also, the data from the small number of beta-EP plasma levels we studied during hot flashes, suggests a possible role of beta-EP either directly or indirectly on the genesis of hot flashes.

Elevated plasma levels of beta-endorphin in a group of women with polycystic ovarian disease.

The relationship of endogenous opiates in patients with polycystic ovarian disease (PCOD) and their influence on body weight was studied. The study group consisted of 19 women with PCOD. They were amenorrheic, hirsute, and hyperandrogenic, and their average weight was 124% of the ideal body weight. They had luteinizing hormone/follicle-stimulating hormone ratios greater than or equal to 2. The control group consisted of ten women with regular ovulatory menses. Plasma beta-endorphin (beta-EP) was measured by using a very specific radioimmunoassay. beta-Lipotropin (beta-LPH) was entirely removed from the sample by preincubation of the plasma with rabbit anti-beta-LPH/Sepharose complex (Pharmacia, New Brunswick, NJ). The mean +/- standard deviation of the plasma beta-EP in the control group was 70.18 +/- 18.06 pg/ml, and the mean +/- standard deviation of beta-EP in the study group was 185.6 +/- 93.4 pg/ml, which was significantly higher than the control levels (P less than 0.001). A significant correlation was also found between plasma beta-EP level and the patient's weight in the PCOD group (r = 0.462, P = 0.025). The data from this study suggest that the elevated levels of endogenous opiates may be involved in the pathophysiology of PCOD and be related to inappropriate secretion of gonadotropins influencing body weight.

Familial 46,XX gonadal dysgenesis.

Two sisters, ages 16 and 17, presented with secondary amenorrhea. In addition, primary ovarian failure, gonadal dysgenesis, and normal karyotypes were demonstrated. The most significant finding was a history of mumps, which they caught at the same time, 10 years before the onset of the amenorrhea. This disorder suggests that etiologic and environmental factors could prevail either in utero or during childhood. These patients are presented to emphasize the importance of considering gonadal dysgenesis as a differential diagnosis in patients with secondary amenorrhea, especially when the menstrual life has been a short one.