Effects of estradiol alone or in combination with cyproterone acetate on carotid artery pulsatility index in postmenopausal women

OBJECTIVES: The incidence of cardiovascular disease (CVD) increases dramatically with the loss of ovarian function. Observational studies indicate that the risk of CVD may be reduced by up to 50% in postmenopausal women who take estrogen replacement therapy. Estrogen therapy reduces internal carotid artery pulsatility index (PI). The improvement in carotid PI following HRT has been proposed as a marker of the cardioprotective effect of estrogen therapy. Cyclical progesterone addition to ERT partially antagonizes the reduction on the carotid artery PI. As progesterone, androgens has been shown to decreases arterial vasodilatation and carotid PI. To our knowledge no information is available regarding the effect of CPA addition on the carotid artery PI in women taking estrogen replacement therapy. METHODS: We recruited a total of 30 women in postmenopause for at least 12 months and were in good health. Fifteen women were postmenopausal following surgical bilateral oophorectomy for benign condition. Fifteen postmenopausal women received estradiol valerate for 21 days and CPA (1 mg) for 10 days for 3 months (Group E/CPA). Ovarectomized women (n=15) received estradiol hemihydrate (2 mg) for 3 months (Group E). The main factor investigated was PI, an indicator of impedence to blood flow down stream. Doppler US were performed before the start and at the end of the therapy. RESULTS: The mean reductions respect to basal values were 11.5% in women treated with E and 10.8% in women treated with E/CPA. No significant difference was found between treatment values. CONCLUSIONS: The results of the present study demonstrate that cyproterone acetate addition to E do non-antagonize the effect of estrogen on carotid artery PI. The present study demonstrate that both estradiol hemihydrate and estradiol valerate plus cyproterone acetate lead to similar improvement in carotid artery; through this mechanism both treatments could potentially reduce the incidence of cerebrovascular disease in postmenopausal women.     

Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss.

BACKGROUND: Uterine perfusion appears to regulate uterine receptivity. However, vascular changes in recurrent pregnancy loss (RPL) remain poorly studied. METHODS: One hundred and twenty one women were enrolled into this study: normal women with sterility caused by male factor (control group: n = 72) and women with RPL (n = 49). Women with uterine anomaly, impaired glucose tolerance, abnormal thyroid function, or anti-phospholipid antibodies were excluded from the study. In the mid-luteal phase of a non-pregnant cycle, transvaginal pulsed Doppler ultrasonography of the uterine artery was performed. Uterine arterial pulsatility index (PI), endometrial thickness, serum estradiol, progesterone, and nitrite/nitrate concentrations were determined. RESULTS: In the RPL group, the PI in the uterine artery of women with antinuclear antibodies was significantly higher than that of women without antinuclear antibodies (P < 0.05). Among women without antinuclear antibodies, the mean (+/-SD) uterine artery PI in the RPL group (2.44 +/- 0.41) was also significantly higher than in the control group (2.19 +/- 0.40; P < 0.01). The PI was inversely correlated with serum progesterone levels (r = -0.47, P < 0.01). CONCLUSIONS: Elevated uterine arterial impedance is associated with RPL. Pulsed Doppler ultrasonography is useful in identifying women with unexplained RPL who have impaired uterine circulation.     

Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years

OBJECTIVE: To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years. DESIGN: This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized, placebo-controlled, double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a standardized questionnaire. RESULTS: At baseline, 16% of women reported hot flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes, vaginal dryness, or sleep difficulties than those who received placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness, uterine bleeding, or other symptoms often attributed to estrogen, but vaginal discharge was more common in women who received estradiol compared with those who received placebo. CONCLUSION: In this population of older, largely asymptomatic women, ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge. Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger, more symptomatic women.     

Raloxifene therapy does not affect uterine blood flow in postmenopausal women: a transvaginal Doppler study

OBJECTIVE: To monitor the effects of raloxifene therapy on the uterus of postmenopausal women by transvaginal ultrasonography and color flow Doppler. Methods: Twenty-five healthy postmenopausal women were enrolled in this prospective longitudinal study performed at Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeir?o Preto. The patients were treated with raloxifene hydrochloride (60 mg per day) for 6 months. All were submitted to transvaginal ultrasound examination with color flow Doppler (ATL-HDI 3000 equipment) before the beginning and after 1, 3 and 6 months of treatment. Resistance index (RI) and pulsatility index (PI) of the uterine arteries were determined by the Doppler method, being considered as indicators of uterine perfusion. The following variables were analyzed: endometrial thickness, uterine volume, RI, and PI. Data were analyzed statistically by repeated-measures analysis of variance. RESULTS: Before treatment, endometrial thickness was 3.38 +/- 0.73 mm, and similar values were observed after 1, 3 and 6 months of treatment (3.04 +/- 0.82; 3.3 +/- 0.83; and 3.37 +/- 0.79, respectively) (P > 0.05). No significant differences in uterine volume were observed between the pre- and post-treatment periods. Uterine artery perfusion as indicated by RI and PI measured by Doppler also showed no significant variation, with a high impedance flow being maintained throughout treatment. CONCLUSIONS: In the group studied here, raloxifene treatment at the dose of 60 mg per day for 6 months did not induce significant changes in endometrial thickness, uterine volume or uterine artery perfusion, confirming that short-term raloxifene treatment does not affect the uterus of postmenopausal women.     

Early impact of hormone replacement therapy on vascular hemodynamics detected via ocular colour Doppler analysis

Objective: To determine the effects of hormone replacement therapy (HRT) on ocular blood flow.

Study design: In a prospective controlled study, 40 healthy women who presented to the menopause clinic between December 2000 and December 2001 were randomly assigned into the study. The HRT-receiving group was administered estradiol 17-valerate 2 mg the first 11 days, and estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg the next 10 days of the monthly cycle for 6 months. The control group did not receive any HRT for 6 months. The ocular colour Doppler analysis were performed at baseline and after 3 and 6 months. The ocular Doppler analysis was performed in the first half of the cycle in the HRT-receiving group.

Results: Central retinal artery and ophthalmic artery basal Doppler index (peak systolic velocity, end-diastolic velocity, resistive index and pulsatility index) values of the two groups at the beginning of the study did not show any statistically significant difference. Both the right and the left central retinal artery pulsatility index (PI) values of the study group, who received HRT at the end of the third and sixth months, showed a statistically significant decline (paired-samples test, P < 0.05), while the decrease in the resistive indexes was not significant.

Conclusion: These results suggest that 6 months of combined hormone replacement therapy with estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg improves ocular vascular Doppler indices which may be a reflection of cerebral vascular status.     

Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy.

OBJECTIVE: To evaluate the effectiveness of vaginal danazol as progestin supplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), estrogen alone, and placebo. METHODS: Forty healthy women at least 12 months after natural menopause were randomly divided into four treatment groups: Group 1 (n=10), continuous transdermal estradiol (TE) (50 microg/day), plus a monthly 10-day course of MPA (10 mg/day); Group 2 (n=10), continuous TE plus a monthly 10-day course of vaginal danazol (200 mg/day); Group 3 (n=10), TE alone; Group 4 (n=10), placebo. At baseline and during the first, third, and sixth month of treatment, the endometrial thickness was assessed by transvaginal ultrasonography, while the pulsatility index (PI) of the carotid and uterine arteries was assessed by color Doppler. An endometrial biopsy was also performed before and after the treatment. RESULTS: At baseline, no significant differences between ages and other evaluated parameters were present in the four groups. In groups 1, 2, and 3, the values of carotid and uterine PI decreased significantly and similarly during the treatment, while in group 4 they were unchanged. In group 3 only, the endometrium was significantly thicker during treatment than before. No endometrial hyperplasia was present in the four groups at the end of the treatment. CONCLUSIONS: Vaginal danazol seems to be capable of counteracting the mitogenic effect of estrogen on the endometrium without reducing the effectiveness of estrogens to improve peripheral arterial perfusion.     

Carotid and uterine vascular resistance in short-term hormone replacement therapy postmenopausal users

Objective: To compare the short-term effects of oral hormone replacement therapy (HRT) and placebo on carotid and uterine vascular impedance. Methods: 80 postmenopausal women selected from the outpatient clinic of the Hospital Leonor Mendes de Barros in São Paulo, Brazil, were randomized to oral HRT (estradiol 2 mg/norethisterone acetate 1mg—Kliogest^r) or placebo. Carotid and uterine arteries pulsatility indices (PIs) were assessed by color Doppler at baseline, after 4 and 12 weeks of treatment. Seventy-six women completed the trial, 38 in each group. Results: The carotid PI did not decrease significantly in either group. In the uterine arteries, the drop in PI was steeper and greater for HRT women. Drops occurred despite the supposed counteracting effect of norethisterone acetate. In placebo group, there was no significant difference between 4 and 12 weeks of treatment compared with the baseline. The results did not change when analyzed in a real treatment approach. Conclusion: Oral continuous HRT are effective at 12 weeks in reducing impedance to flow in uterine, but not in carotid circulation. These results suggest that the effects of HRT vary by vascular site, and do not have a detectable short-term vascular effect in the carotid area.     

Hormone therapy and ophthalmic artery blood flow changes in women with primary open-angle glaucoma

OBJECTIVE: To compare the effects of hormone therapy (HT) on plasma viscosity and Doppler flow parameters in normal, healthy, postmenopausal women and in women with normal-tension and chronic, open-angle glaucoma. DESIGN: Eight postmenopausal women with glaucoma (group I) and 15 controls (group II) were given HT. The duration of the study was 6 months, and the women were examined in basal condition and at the end of the treatment. All women underwent ultrasonographic evaluation of pelvic organs and color Doppler analysis of uterine, internal carotid, and ophthalmic arteries. Also, plasma viscosity was assayed. RESULTS: The ultrasonographic analysis showed that none of the women presented with irregular endometrial echoes, polyps, or intracavitary fluid. In addition, endometrial thickness never exceeded the normal range (5 mm). Plasma viscosity and Doppler parameters significantly improved during therapy. However, the ophthalmic artery mean improvements of pulsatility index (-43% v -28%; P = 0.001), peak systolic blood flow velocity (+35% v +24%; P = 0.026), and time-averaged maximum velocity (+44% v +32%; P = 0.031) were significantly more evident in the control group than in the glaucoma group. CONCLUSIONS: Although, in people with glaucoma, vasospasm can increase the risk of visual loss by inducing a retrobulbar blood flow reduction, HT seems to beneficially affect the ocular vascularization.     

Long term effects of Tibolone on postmenopausal women with uterine myomas.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of Tibolone (Livial) on uterine myomas volume as well as on uterine arteries pulsatility index (PI) in postmenopausal women. METHODS: This study included 66 naturally menopausal women. Twenty of them (group A) had no uterine myomas; 23 of them (group B) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter less or equal than 2 cm; 23 of them (group C) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter between 2 and 5 cm. The volume of the myomas as well as the pulsatility index of the uterine arteries was assessed by transvaginal ultrasonography every 6 months after administration of Tibolone (2.5 mg daily). RESULTS: No statistically significant difference on myomas volume was found after a 3-year period of Tibolone administration. The uterine artery basal PI was significantly higher in group A compared to that of groups B and C. After 6 months of Tibolone administration the PI in group A was significantly lower compared to the basal one whereas in groups B and C was significantly higher compared to the basal value. CONCLUSIONS: Our results suggest that treating postmenopausal woman with Tibolone on a long-term basis: (a) does not increase the volume of uterine myomas and (b) has an early effect on uterine haemodynamics (decrease of PI in women without myomas and increase of PI in women with myomas).     

A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women

OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on the vaginal blood flow and sexual function in postmenopausal women with previous hysterectomy. DESIGN: Fifty-seven women were randomized to receive either oral (0.625 mg of conjugated equine estrogens per tablet; n = 27) or topical (0.625 mg conjugated equine estrogens per 1 g vaginal cream; n = 30) estrogen administered once daily. All women underwent estradiol measurements, urinalysis, pelvic examination, introital color Doppler ultrasonographies, and personal interviews for sexual symptoms using a validated questionnaire before and 3 months after ET. RESULTS: A higher serum level of estradiol was noted in the oral group compared with the topical group after 3 months of ET. There were significant increases in the number of vaginal vessels and the minimum diastole (P < 0.01), and marked decreases of pulsatility index values (P < 0.01) in both groups after ET. Regarding the systolic peak, we found a significant decrease only in the topical group (P < 0.05). Although the post-ET prevalence of anorgasmia decreased significantly in both groups (P < 0.05), changes in other domains, including the rates of low libido and coital frequency, were not statistically significant (P > 0.05). In the topical group, ET improved sexual function on the vaginal dryness and dyspareunia domains in a statistically significant manner (P < 0.05), but this was not the case in the oral group (P > 0.05). However, the efficacy of oral ET for vaginal dryness and dyspareunia reached 80% and 70.6%, respectively. The corresponding figures of the topical ET were 79.2% and 75%. CONCLUSIONS: The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function, but it may not have an impact on diminished sexual desire or activity. Compared with systemic therapy, topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol.     

Effects of hormone replacement therapy on postmenopausal uterine myoma

OBJECTIVES: To evaluate the effects of sequential continuous hormone replacement therapy (HRT) on myoma size and on pulsatility index (PI) of uterine arteries and to verify the correlation between uterine artery flow impedance and the growth rate of myoma in women receiving HRT. METHODS: In a prospective 1-year study 60 postmenopausal women were enrolled into three study-groups to receive continuous transdermal 17beta-oestradiol 0.05 mg/day plus nomegestrolo acetate 5 mg/day sequentially added: 20 patients (group A) unaffected by uterine myomas, 20 patients (group B) with single asymptomatic myoma <3 cm/14 cm3, 20 patients (group C) with single asymptomatic myoma >3 cm/14 cm3. The changes in myoma volume and in PI were assessed by means of transvaginal ultrasonographic scan every 3 months. The patients with myoma were divided into two subgroups: quiescent myoma (B1, C1) and growing myoma (B2, C2). RESULTS: No significant increase of uterine fibroids volume was found after 1-year HRT (24.14+/-20.02-->28.81+/-30.02 cm3). Six out of eight myomas growing during HRT belonged to group C. The uterine artery basal PI value of group A was significantly higher (P<0.01) than the corresponding PI in group B and C. At 3 months follow-up, uterine artery PI was significantly higher (P<0.01) than the basal value in both group B (1.70+/-0.22-->1.88+/-0.16) and C (1.59+/-0.28-->1.92+/-0.21). The baseline PI values in group B1 and C1 were significantly higher than the baseline values observed in group B2 and C2 (1.76+/-0.17 vs. 1.32+/-0.02, 1.76+/-0.16 vs. 1.24+/-0.08) and significantly lower than those observed in group A (2.39+/-0.47). After 3 months of HRT, the PI values were not significantly higher than the baseline values in groups B1 and C2 (1.76+/-0.17-->1.90+/-0.17; 1.24+/-0.08-->1.74+/-0.16), while they were significantly higher in group C1 (1.76+/-0.16-->2.01+/-0.17). CONCLUSIONS: Sequential continuous HRT does not increase the volume of the uterine myoma. The findings of very low resistance index in the uterine arteries of women with growing myoma may indicate the risk of growth of the neoplasia during HRT. The assessment of PI in the uterine arteries could be helpful in predicting the growth rate of the myomas before starting HRT.     

Doppler ultrasound examination of uterine arteries on the day of oocyte retrieval in patients with uterine fibroids undergoing IVF

BACKGROUND: There is no consensus as to whether uterine fibroids have any adverse effects on the outcomes of assisted reproduction treatment. This prospective study compared implantation/pregnancy rates of women with and without fibroids undergoing IVF-embryo transfer and measured uterine blood flow indices of the fibroid group. METHODS: Patients who had fibroids that, during transvaginal scanning, were found to be not distorting the endometrial lining were placed in the fibroid group, while patients with normal uteri were controls. Those with previous myomectomy or pedunculated subserosal fibroids only were excluded. All received a standard ovarian stimulation regimen. Doppler ultrasound examinations of uterine arteries were carried out in the fibroid group prior to oocyte retrieval. RESULTS: Similar implantation/pregnancy rates, multiple pregnancy rates and pregnancy outcomes were noted in both groups. In the fibroid group, significantly lower pulsatility index (PI) and resistance index (RI) of the right uterine artery and the average of right and left uterine arteries were found in those failing to conceive than in those patients who subsequently conceived (P < 0.001). CONCLUSION: The presence of fibroids not distorting the endometrial lining does not adversely affect implantation and pregnancy rates during IVF-embryo transfer. Significantly lower uterine artery PI and RI were found in non-pregnant women with fibroids than in their pregnant counterparts.     

Diagnostic techniques: Blood flow changes in uterine and ovarian vasculature, and predictive value of transvaginal pulsed colour Doppler ultrasonography in an in-vitro fertilization programme

The role of transvaginal pulsed colour Doppler ultrasound inthe prediction of the outcome of in-vitro fertilization (IVF)therapy was assessed longitudinally in 30 patients during stimulatedcycles. The pulsatility index (PI) of the uterine arteries didnot change significantly until the mid-luteal phase. Within6 days after the beginning of stimulation the maximum peak systolicvelocity of the uterine blood flow had increased significantlyfrom 27.6 ± 8.9 to 36 ± 12.8 cm/s. No differencewas found in uterine PI between pregnant and non-pregnant women.The PI of intra-ovarian flow was also similar in both groups.However, there was an insignificant increase in uterine receptivitywhen the PI of the uterine artery was between 2.0 and 2.99 onthe day of embryo transfer. Nevertheless, the appraisal of theprognostic outcome of the treatment could not be made with Doppler.     

The effects of a copper-intrauterine device on the uterine artery blood flow in regularly menstruating women

The aim of the study was to evaluate the effect of a copper- intrauterine device (IUD) on uterine artery blood flow during the midluteal phase and on the first day of the menstrual cycle using pulsed colour Doppler ultrasonography. Twenty-one regularly menstruating women (18-45 years) who were willing to use copper-IUD contraception participated in the study. The patients were first examined without the IUD in the midluteal phase 6-9 days before the expected onset of menstruation and on the first day of menstruation, after which the IUD was inserted. Three months later the patients were examined again on the corresponding cycle days. The patients estimated the level of dysmenorrhoeic pain with a scoring system. Transvaginal ultrasonography with colour flow imaging was used to measure the pulsatility index (PI) in the uterine arteries. There were no significant changes in the uterine artery blood flow after the insertion of the IUD during menstruation or in the midluteal phase. In patients with increased IUD-related pain during menstruation (n = 5), however, there was a decrease in PI (2.87 +/- 0.52 versus 2.41 +/- 0.23, P = 0.05) after IUD insertion. The decrease in the mean PI was present in all five patients. In conclusion, copper-IUD does not induce any major changes in the resistance of the uterine artery blood flow, although during menstruation in patients with increased menstrual pain after IUD insertion there seems to be a decrease in the uterine artery PI.      

Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment

BACKGROUND: The impact of intramural fibroids on the success of IVF treatment is controversial and the mechanisms leading to poor treatment outcomes remain unknown. We compared endometrial and subendometrial blood flow between women with and without intramural fibroids during IVF treatment. METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed on the day of oocyte retrieval in 50 patients with intramural fibroids not distorting the uterine cavity and in 50 matched controls to measure endometrial thickness, uterine pulsatility index (PI)/resistance index (RI), endometrial volume and vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. Smokers, patients with serum estradiol concentrations > or =20,000 pmol/l on the day of HCG and previous history of myomectomy were excluded. RESULTS: Endometrial thickness and pattern, averaged uterine PI and RI and endometrial and subendometrial VI/FI/VFI were similar between the fibroid group and the control group. There was no correlation between the total volume of fibroids and endometrial and subendometrial 3D power Doppler flow indices in the fibroid group. CONCLUSION: Endometrial and subendometrial 3D power Doppler flow indices were similar in patients with and without small intramural fibroids.     

The effect of HRT on cerebral haemodynamics and cerebral vasomotor reactivity in post-menopausal women

BACKGROUND: Cerebral vasomotor reactivity (CVR) is an index of cerebrovascular dilatory capacity which can readily be assessed using trans-cranial Doppler ultrasound. Impaired CVR is associated with elevated risk of stroke. We performed a randomized, double-blind placebo-controlled trial to investigate the effect of two HRT preparations upon CVR. METHODS: We examined middle cerebral artery mean flow velocity (MFV), internal carotid artery pulsatility index (PI) and CVR to an i.v. acetazolamide bolus using ultrasound in three groups of post-menopausal women randomized to oral estradiol 1 mg+norethisterone 0.5 mg (group N), estradiol 1 mg+dydrogesterone 5 mg (group D) or placebo (group P). The MFV, PI and CVR were measured before and after 3 months treatment. RESULTS: Thirty-eight post-menopausal women were recruited (N=12, D=14, P=12); mean (SE) age was 56.7 (4) years. Neither HRT preparation affected CVR [% (SE) change from baseline N +4.2 (11); D +3.8 (5.5); P +4.0 (3.8); all comparisons P = NS]. PI was significantly reduced in recipients of dydrogesterone [% (SE) change from baseline D -5.4% (4.6); N +12.3 (6.9); P +11.6 (6.9). P=0.025]. Middle cerebral artery velocity was significantly increased following dydrogesterone treatment compared with placebo [% (SE) change from baseline D +6.8 (3.4) N +3.9 (4.2) P -4.6% (3.4) P=0.03 for D versus P]. CONCLUSION: HRT did not alter CVR. The reduced PI and increased MFV suggest HRT-induced intracranial vasodilatation, which is more apparent in dydrogesterone recipients. Differences may exist between progestogens with regard to changes in intracranial haemodynamics.     

Plasma adiponectin levels in postmenopausal women with or without long-term hormone therapy

OBJECTIVE: Recent large, prospective, randomized studies show that hormone therapy (HT) does not confer a protective effect against cardiovascular disease (CVD) but may in fact increase cardiovascular events. Low plasma adiponectin levels are considered to be related to the development of atherosclerosis and CVD. The purpose of this study was to determine the effect of long-term hormone therapy on plasma adiponectin levels in postmenopausal women. METHODS: We recruited a total of 88 postmenopausal women aged 55-69 years old. Our sample consisted of 44 women who had undergone estrogen plus progestogen therapy (EPT) for more than 5 years and 44 age-matched women who had not received HT. We measured plasma adiponectin levels, the serum levels of their lipid profiles, high-sensitivity C-reactive protein (hs-CRP), fasting glucose levels, fasting insulin levels and estradiol levels. Their medical histories including their age at menopause, vitamin use, exercise, alcohol ingestion and cigarette smoking were also assessed by a questionnaire. RESULTS: The mean duration (mean+/-S.D.) of HT was 8.4+/-2.4 years. The mean serum estradiol level (mean+/-S.D.) of the HT group was 47.9+/-36.8 pg/L, significantly higher than that of the non-HT group (p<0.01). Plasma adiponectin levels were significantly lower in the HT group than in the non-HT group (p<0.05). Plasma adiponectin levels were inversely correlated to cholesterol, triglycerides and HOMA-IR (r=-0.33, p<0.05; r=-0.40, p<0.01 and r=-0.30, p<0.05, respectively) in the non-HRT group, but such correlations were not seen in the HT group. In the multivariate analysis, hormone therapy and serum estradiol levels were the independent factors associated with plasma adiponectin levels after adjustments were made for potential confounders. CONCLUSION: Plasma adiponectin levels were significantly lower in postmenopausal women with long-term HT than in those without HT, suggesting that long-term HT may modulate plasma adiponectin level in postmenopausal women.     

Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy.

Doppler ultrasound was used to investigate circadian variations in uterine artery blood flow in 20 post-menopausal women in the oestrogen-only phase of combined oestrogen hormone replacement therapy with cyclical oral norethisterone or dydrogesterone. All women were examined between 0800 and 0830 h and then again between 1800 and 1830 h on the same day. Mean arterial blood pressure, heart rate and a blood sample for measurement of serum oestradiol were taken at each visit. Indices of uterine artery blood flow included the pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity. No significant differences in the mean arterial blood pressure, pulse rate and oestradiol concentrations were detected between morning and evening visits. Significant fluctuation was observed in the pulsatility index (P < 0. 001), resistance index (P < 0.001) and time-averaged maximum velocity (P < 0.01). The assessment of uterine artery blood flow in post-menopausal women should take into account the presence of circadian variations to ensure accuracy and reproducibility of Doppler investigations.     

Clinical effects of a standardized soy extract in postmenopausal women: a pilot study

OBJECTIVE: This double-blind, randomized study was aimed at evaluating comparatively, in postmenopausal women, the activity of a standardized soy extract (SOYSELECT) and placebo when given alone or in combination with conjugated equine estrogens (CEE) on early climacteric symptoms. Lipid profile, pituitary hormones, osteocalcin and endothelin levels, and vaginal and endometrial parameters were also evaluated. DESIGN: Participants in the control group were given placebo, and participants in the treated group were given 400 mg/day of a standardized soy extract, corresponding to 50 mg/daily of isoflavones. After 6 weeks of treatment, CEE was also then given to each participant at a dose of 0.625 mg/day for 4 weeks. At the end of this period, soy and placebo treatment were suspended, and, until the end of the study (week 12), participants were administered 10 mg/day of medroxyprogesterone acetate in association with CEE (0.625 mg/day). RESULTS: When compared with pretreatment data, on week 6 of the study, a significant (p < 0.01) reduction in the mean number of hot flushes per week was observed in participants who were receiving the standardized soy extract, whereas a more marked relief was observed in both soy and placebo groups during CEE administration. Concurrently, the severity of hot flushes, assessed by means of the Greene climacteric scale, was also reduced in the soy group participants (p < 0.001, by paired t-test). No soy-related changes were observed on vaginal cytology, endometrial thickness, uterine artery pulsatility index, or metabolic and hormonal parameters tested. Finally, CEE-related changes on genital tract, uterine vascular compartment, and pituitary hormones were not modified by soy treatment. CONCLUSIONS: SOYSELECT may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy.     

No evidence of increased uterine vascular impedance with patient ageing following IVF

A study was conducted to determine if uterine vascular impedance increases with advancing age in women undergoing ovarian stimulation for IVF. A group of 162 women who had undergone conventional IVF and embryo transfer was subdivided into three subgroups by age: 30-34 years (n = 49), 35-39 years (n = 79) and 40-44 years (n = 34). The pulsatility index (PI) and resistance index (RI) of the right and left uterine arteries were measured at baseline, on the day of oocyte retrieval, and at the mid-luteal phase. There were no differences in the average PI or RI by age at any phase of the cycle. In all age groups, the luteal phase values of PI and RI were lower than those observed earlier in the cycle. Endometrial thickness was not associated with age. There was no significant correlation between PI, RI and serum oestradiol and progesterone concentrations at any phase of the cycle. Ovarian response, as measured by average number of oocytes retrieved, decreased significantly with age. Thus, reduced pregnancy rates in older women undergoing ovarian stimulation are more likely to occur because of oocyte quality and quantity rather than uterine senescence. If future studies determine that the use of ovarian stimulation does decrease implantation rates more in older versus younger women, a mechanism other than increased uterine vascular impedance must be sought.