Cervical length and risk of antepartum bleeding in women with complete placenta previa.

OBJECTIVE: To evaluate if cervical length predicts prepartum bleeding and emergency Cesarean section in cases of placenta previa. METHODS: Between September 2005 and September 2007, cervical length was measured by transvaginal ultrasound in women with complete placenta previa persisting into the third trimester of pregnancy. A complete follow-up of pregnancy was obtained in all cases. RESULTS: Overall, 59 women were included in the study group. The mean +/- SD gestational age at ultrasound was 30.7 +/- 2.7 weeks and the cervical length was 36.9 +/- 8.8 mm. Cesarean delivery was performed in all cases, at a mean gestational age of 34.7 +/- 2.3 weeks. Twenty-nine (49.1%) of the women presented prepartum bleeding and 12 (20.3%) required an emergency Cesarean section prior to 34 completed weeks due to massive hemorrhage. Cervical length did not differ significantly between cases with and those without prepartum bleeding (35.3 +/- 9.3 mm vs. 38.4 +/- 8.2 mm; P = 0.18), but was significantly shorter among patients who underwent emergency Cesarean section < 34 weeks due to massive hemorrhage compared with patients who underwent elective Cesarean section (29.4 +/- 5.7 mm vs. 38.8 +/- 8.5 mm; P = 0.0006). CONCLUSIONS: Transvaginal sonographic cervical length predicts the risk of emergency Cesarean section < 34 weeks in women with complete placenta previa.

Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.

BACKGROUND: The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. AIM: To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. MATERIALS AND METHODS: Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. RESULTS: Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups. CONCLUSIONS: Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

Phalangeal osteosonogrammetry study: age-related changes, diagnostic sensitivity, and discrimination power. The Phalangeal Osteosonogrammetry Study Group.

Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude-dependent speed of sound [AD-SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD-SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X-ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD-SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD-SOS was odds ratio (OR) 1.71 (CI, 1.58-1.84). The AD-SoS in fractured subjects was significantly lower than in a group of age-matched nonfractured subjects (p < 0.0001). In a small cohort of hip-fractured patients UBPI proved to be lower than in a control age-matched group (p < 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD-SoS we found a T score of -3.2 and for UBPI we found a T score of -3.14. Sixty-six percent of vertebral fractures were below the AD-SoS -3.2 T score and 62% were below UBPI -3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD-SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.

The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group.

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Monitoring bone effect of transdermal hormone replacement therapy by ultrasound investigation at the phalanx: a four-year follow-up study.

OBJECTIVE: A controlled 4-year follow-up study was conducted on a population composed of 112 healthy early postmenopausal women to evaluate the ability of ultrasound technology in detecting the effects of hormone replacement therapy (HRT) on bone. At the end of the study, 47 untreated and 25 treated women had been evaluated. Cyclic sequential estrogen/progestogen therapy, 50 microg/day of transdermal 17beta-estradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone (Wyeth-Ayerst) was used. DESIGN: Ultrasound transmission through the distal metaphysis of hand phalanxes was measured by DBM Sonic. Beside amplitude-dependent speed of sound (AD-SoS), three new parameters could be calculated: pure speed of sound (pSOS), bone transmission time (BTT), and ultrasound bone profile index (UBPI). Ultrasound measurements were taken at baseline and after 1, 2, and 4 years. RESULTS: Among untreated women a significant decrease of all ultrasound parameters was observed at follow-up measurements. In the HRT-treated group we observed a significant increase of AD-SoS, pSoS, and BTT. We qualified as "responders" women in the treated group for whom AD-SoS, pSoS, and BTT increased by more than 2.77 times the coefficient of variation of the measurement, i.e., 95% variability. Women in the treated group were identified as responders at 4 years of follow-up by AD-SoS (56%), pSOS (56%), and BTT (60%). Ultrasound bone profile index declined in both groups, although to a lower extent among HRT-treated subjects. CONCLUSIONS: The 4-year data confirm the results obtained at 1 and 2 years of follow-up. This study demonstrates that bone tissue investigation by ultrasound at the phalanx can be used to monitor the effect of HRT, and thus it should be considered a potential technology for the management of menopause by gynecologists.

Morning sickness control in early pregnancy by Neiguan point acupressure.

OBJECTIVE: To evaluate the antiemetic effect of acupressure at the Neiguan point. METHODS: Sixty women in early pregnancy were entered into a randomized, double-blind, cross-over, placebo-controlled trial. During a 12-day period, organized in four steps of 3 days each, the women were divided into two homogeneous groups to test the effectiveness of unilateral and bilateral acupressure. RESULTS: Use of acupressure resulted in a significantly lower frequency of morning sickness compared with placebo treatment. More than a 60% positive effect was found with unilateral and bilateral acupressure, compared with an approximately 30% positive effect of placebo acupressure. Changing from unilateral to bilateral pressure on the Neiguan point caused no significant statistical difference. No noteworthy side effects occurred. CONCLUSION: Acupressure on the Neiguan point relieves morning sickness.

The effect of dietary soy supplementation on hot flushes.

OBJECTIVE: To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in postmenopausal women. METHODS: We carried out a double-blind, parallel, multicenter, randomized placebo-controlled trial of 104 postmenopausal women. Fifty-one patients (age range 48-61 years) took 60 g of products containing 40 g of isolated soy protein [corrected] daily and 53 patients (age range 45-62 years) took 60 g of placebo (casein) daily. The study lasted 12 weeks. Using analysis of covariance, we analyzed changes from baseline in mean number of moderate to severe hot flushes (including night sweats) during treatment. RESULTS: Soy was significantly superior to placebo (P < .01 in reducing the mean number of hot flushes per 24 hours after 4, 8, and 12 weeks of treatment. In particular, women taking soy had a 26% reduction in the mean number of hot flushes by week 3 and a 33% reduction by week 4 (P < .001 by the Wilcoxon exact test). By the end of the 12th week, patients taking soy had a 45% reduction in their daily hot flushes versus a 30% reduction obtained with the placebo (P < .01). The overall rates of adverse effects were similar for soy and casein-placebo. Twenty-five patients dropped out of the study: 11 in the soy group and 14 in the placebo group. Gastrointestinal side effects were the most common cause of premature withdrawal from the study (seven patients in each group). CONCLUSION: Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women.

Dietary soy supplementation and phytoestrogen levels.

OBJECTIVE: To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. METHODS: Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. RESULTS: Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. CONCLUSION: Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.

Plasma catecholamines in pre- and in postmenopausal women with mild to moderate essential hypertension.

The sympathetic nervous system (SNS) is thought to play an important role in the pathogenesis of essential hypertension and many studies have established a relationship between plasma levels of norepinephrine (NE) and epinephrine (E) and sympathetic nervous activity (SNA). Furthermore, it has been suggested that climacteric women are more exposed to psychosocial stress which can produce a transient rise in blood pressure (BP) and, with time, determine a hypertensive state. Plasma NE and E levels were measured at rest and after physiological stimulation (head-up tilt test) in 20 hypertensive (BP: 146 +/- 13/101 +/- 4 mm Hg) and in 20 normotensive women (BP: 132 +/- 7/85 +/- 4 mm Hg). Women in each of these two groups were further subdivided according to their climacteric status (10 premenopausal and 10 postmenopausal women). No difference in NE values at rest was found between groups and subgroups. During head-up tilt test, Ln NE plasma values increased in normotensive and hypertensive groups; the rise was significantly higher in hypertensive than in normotensive women (P < 0.01). In climacteric subgroups, Ln NE appeared markedly increased above resting levels in pre- and postmenopausal hypertensive women when their position was changed from supine to upright (P < 0.01). Since high plasma NE levels after stimulation (head-up tilt) are associated with sympathetic overactivity, we conclude that SNA is involved in the pathogenesis of essential hypertension in climacteric women.

Female sexual activity as a function of climacteric conditions and age.

By establishing a statistical profile of the average sexual behaviour of women during the climacteric period, an attempt was made to determine what influence the climacteric had on female sexual activity. With the advancement of age, the sexual activity of women tends to decline. The menopause itself tends to further reduce the retrogression of the sexual activity in women.

Analysis of the climacteric syndrome.

The climacteric syndrome (CS) was investigated in a large sample of women (over 4000) who spontaneously attended the Menopause Clinic at the University of Bologna between 1976 and 1986. The participants selected had received no hormonal replacement therapy for at least 6 mth or any other drug for at least 3 mth previously. They were all free from any disease that could influence any of the CS symptoms. The frequency of 12 symptoms considered typical of the CS was investigated. The interrelationships between these symptoms were determined as well as the frequency of the occurrence of individual symptoms in association with various climacteric complaints. The results indicated (a) that the CS is not uniform but both variable and individual, (b) that the frequency of its constituent symptoms remains high in advanced fertile age and the advanced postmenopause, (c) that the symptoms are preferentially interlinked, (d) that many, but not all, symptoms exhibit a differentiated pattern during the course of the natural and surgical menopause/age progression, and (e) that hot flushes and sweating, and to some extent insomnia and headache, are menopause-dependent.

Use of Org OD 14 for the treatment of climacteric complaints.

The effects of treating climacteric complaints in post-menopausal women were studied in an open trial in which Org OD 14, a placebo and no treatment were compared. In addition to the symptomatic effects, clinical and laboratory parameters were also studied. One hundred and twenty-four women who had undergone a natural or surgical menopause completed 4 mth of randomized treatment; 35 received Org OD 14 (2.5 mg/day, per os), 46 a placebo, and 43 no treatment. The mean ages and time in years since menopause were comparable for each group. The parameters were assessed before treatment and after 4 mth. The results in the group treated with Org OD 14 were compared statistically with those for the other two groups using the chi 2 test, Student's t test or analysis of variance. A beneficial effect on clinical parameters was seen following Org OD 14 treatment. The results as regards hot flushes and sweating were significantly better statistically than those in the other groups. Org OD 14 was found to have no effect on the endometrium, breasts, body weight or blood pressure, while vaginal atrophy was slightly improved. Serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and phosphate were slightly reduced by Org OD 14. Liver function tests, clotting factors and the other routine laboratory parameters were not affected by Org OD 14 treatment. It was concluded that Org OD 14 is an effective and safe compound for the treatment of climacteric syndrome.

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT.

OBJECTIVES: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. METHODS: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. RESULTS: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. CONCLUSIONS: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth.

High blood pressure and 'ischaemic' ECG patterns in climacteric women.

A study to evaluate the prevalence of high blood pressure (HBP) and resting 'ischaemic' electrocardiogram (ECG) patterns in the climacteric was carried out in 494 outpatients aged up to 65 yr. The study group was made up of 91 pre-menopausal women, 235 natural post-menopausal women, 91 surgical post-menopausal women and 77 women of advanced reproductive age, who comprised the control group. High systolic and/or diastolic blood pressure values were seen in 26.6% of the overall climacteric group (C), i.e. in 23.1% of the pre-menopausal women (PM); 28.9% of the natural post-menopausal women (NMt); and 24.2% of the surgical post-menopausal women (SMt), these frequencies being statistically significant compared to that in the control group (K) (6.5%). 'Ischaemic' ECG patterns (according to the Minnesota Code definition) were observed in 20.3% of the C group, in 22.0% of the PM group and in 27.5% of the SMt group, these rates being statistically significant compared to that in the control group (9.1%). Minnesota Code 4:1 and 5: 1-2 patterns were present in 5.7%, and 4:2 and 5:3 patterns in 14.6% of the C group. A significant correlation was found between HBP (systolic and diastolic) and 'ischaemic' ECG patterns.

Non-invasive 24-hr monitoring of high blood pressure in climacteric outpatients.

Blood pressure (BP) monitoring was carried out over a period of 24 hr in 28 hypertensive women selected among the outpatients attending the Menopause Clinic at Bologna University. Seven (7) of the women (mean age 50 +/- 1 yr) were in the pre-menopause, 7 had undergone a natural menopause at 6 to 36 mth previously (mean age 52 +/- 4 yr) and a further 7 had had a natural menopause 37-120 months previously (mean age 56 +/- 5 yr). The control group was made up of 7 women in late fertile age (mean age 47 +/- 1 yr). It was found that: high blood pressure was not confirmed in all patients; there was a significant increase in systolic and diastolic BP values in natural post-menopause subjects (P less than 0.01) temporarily related to ovarian failure, but BP reached a steady state in elderly women when a new hormonal balance is established; 24-hr monitoring made it possible to identify a group of climacteric outpatients at higher cardiovascular risk whose suitability for antihypertensive treatment could thus be assessed.

A study of thyroid function in the pre- and post-menopause.

Serum levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triidotthyronine (FT3), free thyroxine (FT4) and thyroxine-binding globulin (TBG) were measured in 382 healthy women who were attending a menopause clinic. Of these women, 140 were in the pre-menopausal phase, 162 had been post-menopausal for less than 3 yr and 60 had been post-menopausal for greater than 3 yr. Analysis of the results as a function of climacteric situation, revealed that the only significant difference was a lower serum concentration of FT3 in the women who had been post-menopausal for over 3 yr than in the women who were in the pre-menopausal phase. Statistical analysis of the results as a function of both climacteric situation and age showed that the serum level of TBG increases with age, while serum levels of circulating thyroid hormones decrease, and that although the menopause does not bring about marked changes in thyroid function, it nevertheless tends to reduce that function, especially when menopause occurs at the expected time. Finally, by correlating values with T4 values on an individual basis, it was possible to ascertain that when physiological changes in thyroid function do occur in the climacteric, they are not caused by primary changes in TSH secretion.

Physiopathological aspects of body overweight in the female climacteric.

The correlation between overweight and the climacteric was studied in 550 menopause clinic patients by investigating certain clinical and sociocultural parameters (age, marital status, educational level, occupation and type of work, calorie intake, smoking habits, parity, blood pressure, previous hormonal therapy and climacteric symptoms), evaluating plasma levels of various hormones (17 beta-oestradiol, follicle-stimulating hormone (FSH), luteinizing (LH), testosterone, hydrocortisone, adrenocorticotrophic hormone (ACTH), triiodothyronine (T3), thyroxine (T4), growth hormone (GH) and insulin), glucose and various lipid fractions (total lipids, total cholesterol, nonesterified fatty acids (NEFA), triglycerides and phospholipids) and exploring the blood-clotting pattern ( Owren 's test, euglobulin lysis time, antithrombin III and prothrombin agglutination time (PAT). The subjects were classified as normal weight or overweight by reference to Broca's Index, as modified by Brusch , and the degree of overweight was determined by means of the Body Mass Index (BMI). Of the subjects examined, 49% were overweight and, in successive years following the menopause, there was a growing bipolarization of the weight increase. The correlation between overweight in the climacteric and the parameters considered was found to be significant only in regard to calorie intake, age and educational level. Post-menopausal gonadotrophin levels in blood were significantly lower in the overweight than in the normal-weight women. With the onset of menopause, the plasma level of testosterone fell in the normal-weight women, while it increased, along with that of hydrocortisone, in the overweight women. In the normal-weight women at menopause, it was found that there was a tendency towards a substantial increase in lipid fractions and glycaemia, as well as a state of hypercoagulability. In the overweight women, the tendency was towards an even more marked increase in both glycaemia and the various lipid fractions, and, besides the hypercoagulative state, there was an associated reduction in fibrinolytic activity. It is concluded that the menopause not only causes metabolic changes but also aggravates the metabolic and endocrine tendencies which characterize overweight subjects and thus, clinically, constitutes an obesity risk factor in those women who already demonstrate a tendency towards overweight in the pre-menopausal phase.

Body mass index distribution in climacteric women.

Body Mass Index (BMI) was calculated in 2481 climacteric women selected from among the outpatients attending the Menopause Clinic at Bologna University in absence of hormonal replacement therapy and diseases that could cause weight gain. Analysis of variance of the W/H2 (weight/height squared) distribution in different age and climacteric situations demonstrates that the pre-menopause is a weight-gain inducing state and that ageing seems to cause a progressive increase in W/H2.

Bone effects of transdermal hormone replacement therapy in postmenopausal women as evaluated by means of ultrasound: an open one-year prospective study.

OBJECTIVES: To evaluate the effectiveness of transdermal oestrogen replacement therapy plus medrogestone (HRT) in postmenopausal bone loss prevention by means of US. METHODS: We enrolled 112 healthy postmenopausal women in an open, prospective study. These women, after a gynaecological evaluation and an US assessment of the skeletal status, were advised to take cyclic sequential oestrogen/progestagen therapy: 50 microg/day of transdermal 17beta-oestradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone, for 12 days per cycle (Wyeth-Ayerst). After 1 year we recalled these women: only 32 of them were taking HRT, while 49 had declined HRT without taking alternative therapies. The remaining women were excluded from the study as they were either unavailable for the check-up or they were taking prohibited therapies. We used DBM Sonic 1200 (Igea, Italy) to assess US parameter changes at phalanxes at enrollment and after 1 year. This device enabled us to evaluate US transmission velocity (AD-SoS) and US attenuation pattern (UBPS). In a previous study we had evaluated the intra- and inter-observer reproducibility of AD-SoS measurements (0.4 and 1.0% respectively). Using the same data we evaluated the intra- and inter-observer precision of UBPS. RESULTS: The UBPS intra-operator reproducibilities were 5.3% and 6.1% (for the 1st and the 2nd operator, respectively), while inter-observer precision was 8.8%. Both AD-SoS and UBPS significantly decreased in the non-user group(-0.7%, P < 0.001 and -14.3%, P < 0.001 respectively). In the user group AD-SoS showed a significant increase (+0.7%, P < 0.01), while a slight but significant decrease was observed for UBPS (-2.8%, P < 0.05). CONCLUSIONS: Our findings show that the effectiveness of transdermal HRT in slowing or even arresting postmenopausal bone loss can be monitored by quantitative US studies. The trend difference observed between AD-SoS and UBPS with and without therapy is at least partially explained by a different response to HRT with regard to bone density as well as structure.