Paraovarian/paratubal cysts: comparison of transvaginal sonographic and pathological findings to establish diagnostic criteria.

OBJECTIVES: To describe the sonographic features of paraovarian cysts and to compare these features with pathological findings in order to define the best treatment options (surgical vs. conservative). METHODS: Fifty patients (mean age 48 (range, 14-68) years), each with a surgically proven paraovarian cyst, were retrospectively recruited. Preoperative transvaginal ultrasonographic B-mode and power Doppler observations were re-evaluated and histological reports were analyzed. RESULTS: All cysts were correctly diagnosed as paraovarian at preoperative transvaginal sonography (TVS). Paraovarian cysts appeared as unilocular ('simple') cysts in 33 (66%) cases and multilocular in two (4%). In 15 patients (30%) the cyst showed a variable number of papillary projections growing from the cyst wall (unilocular-solid cysts). Power Doppler examination of the papillae showed the presence of blood vessels in four of these patients (27%). Histological analysis of the masses containing papillary projections diagnosed eight cystadenofibromas, five cystadenomas and two serous papillary borderline tumors, while analysis of paraovarian cysts without papillations revealed benign, serous cysts of paramesonephric or mesothelial origin. CONCLUSIONS: Paraovarian cysts can show a wide range of sonographic features. Their risk of malignancy is low if no papillary projections are detected at transvaginal sonography, but when mural proliferations are present a borderline tumor can be found at pathological examination.

Transvaginal sonographic features of peritoneal carcinomatosis.

OBJECTIVES: Peritoneal carcinomatosis involves the dissemination of intra-abdominal tumor tissue often associated with gynecological malignancies. The objective of this study was to describe the transvaginal sonographic appearance of this condition. METHODS: The data of 60 patients with surgically and histologically proven peritoneal carcinomatosis were analyzed. Transvaginal sonograms performed within 7 days of admission to the operating theater were re-evaluated in order to identify the sonographic features associated with peritoneal carcinomatosis. RESULTS: Carcinomatosis was revealed in 53/60 cases (88%) by the presence of hypoechoic nodules attached to the peritoneum and visible on transvaginal sonography (TVS). The pouch of Douglas was the site most frequently involved. Power Doppler sonography showed the presence of blood vessels in 48 (91%) of these metastases. Ascites was found in 50 (83%) women. An adnexal mass suggestive of being the primary tumor was present in only 41 women (68%). CONCLUSIONS: Peritoneal carcinomatosis has typical features on TVS and, in the vast majority of cases, its genital origin can be correctly hypothesized. Power Doppler sonography strengthens the diagnosis by showing vascularity of the peritoneal implants. In a patient with a known pelvic malignancy or whenever peritoneal carcinomatosis is suspected, TVS can give useful information in order to better assess the presence and extension of metastatic nodules within the abdominal cavity.

Transvaginal sonographic appearance of peritoneal pseudocysts.

OBJECTIVE: To describe the sonographic features of peritoneal pseudocysts (PPCs) in order to determine the particular aspects that distinguish them from true ovarian cysts. METHODS: Thirty-one women with PPCs were investigated using transvaginal sonography immediately before surgery. The diameters of the cysts were measured, and the shape, margins, content, location, presence of septa and echogenic portions were analyzed. RESULTS: The PPCs were monolateral in 20 (65%) and bilateral in 11 (35%) women. A well-defined cystic structure was found in only six (19%) women, while in the other 25 (81%) women the PPCs showed blurred, undefined margins and a bizarre morphology, giving them a star-like tubular or lumpy shape. The ipsilateral ovary was identified in 26 (84%) cases either external to the cyst or entrapped within it like a 'spider in a web'. Septa were present in 25 (81%) cases and were often mobile, resembling a 'flapping sail' when touched by the endovaginal probe. CONCLUSION: Despite having a gross morphology resembling that of a true ovarian cyst, PPCs present some characteristic sonographic findings that allow a correct differential diagnosis in the vast majority of cases.

Comparison of uterine and spiral artery blood flow in women with unexplained and tubal infertility.

OBJECTIVE: To evaluate the possible difference in uterine and spiral artery impedance to blood flow among women with unexplained and tubal infertility during spontaneous and gonadotropin-stimulated cycles. METHODS: We prospectively compared uterine and spiral artery pulsatility index and peak systolic velocity in a longitudinal study in women with either unexplained infertility (n = 20) or tubal infertility (n = 18). Measurements of uterine and spiral artery impedance were taken on days 11-12, 16-17 and 21-23 of the spontaneous cycle and on days 1, 5 and 10 during gonadotropin stimulation. In addition, measurements were taken on the days of oocyte pick-up and embryo transfer. RESULTS: A clinical pregnancy was achieved in 8/20 (40%) women with unexplained and 6/18 (33.3%) women with tubal infertility with in-vitro fertilization treatment. There were no differences in the uterine artery pulsatility index or peak systolic velocity during the spontaneous or the in-vitro fertilization cycle between the two groups. The impedance to blood flow in the uterine or spiral artery did not differ between women conceiving with in-vitro fertilization-embryo transfer and those who did not. However, the spiral artery pulsatility index on the 5th day of gonadotropin stimulation was significantly lower among women with unexplained infertility (0.96 +/- 0.25) compared to women with tubal infertility (1.24 +/- 0.30; P < 0.05), but on the other days of gonadotropin stimulation the spiral artery pulsatility index and peak systolic velocity were similar. CONCLUSIONS: Impaired uterine or spiral artery blood flow is not an important factor in unexplained infertility.

Transvaginal sonography in the diagnosis of acute appendicitis.

OBJECTIVES: To evaluate transvaginal sonography with power Doppler capacity in the diagnosis of acute appendicitis and in discriminating appendicitis from pelvic inflammatory disease. PATIENTS AND METHODS: We describe transvaginal sonographic findings of six women with acute appendicitis selected from 31 women seen in an emergency room setting for clinically suspected pelvic inflammatory disease. The study population underwent gray-scale transvaginal sonography, and specific sonographic landmark findings for acute appendicitis and pelvic inflammatory disease were used. Hyperemia of any infectious complex was identified by power Doppler. Laparoscopy was performed after transvaginal sonography and was used as the gold standard. RESULTS: Laparoscopy showed acute appendicitis in six (19%) of the 31 patients. A thick walled non-compressible gas-containing tubular structure with a diameter exceeding 6 mm was seen by transvaginal sonography in four of the six cases, consistent with uncomplicated appendicitis. A heterogeneous complex with surrounding hyperechogenic soft tissue was seen in two cases with gangrenous appendicitis. Power Doppler detected hyperemia in all six cases. Normal adnexal structures were imaged next to the inflamed appendix. The sonographic criteria consistent with acute appendicitis were clearly different from those of acute pelvic inflammatory disease. CONCLUSIONS: Transvaginal sonography provides an opportunity to distinguish between appendicitis and acute pelvic inflammatory disease. Prospective trials are needed in order to evaluate the impact of transvaginal sonography in the diagnosis of acute appendicitis.

Paraquat embryotoxicity in the Xenopus laevis cleavage phase.

The high Paraquat (PQ, 1-1'-dimethyl-4,4'bipyridylium dichloride) embryotoxicity in Xenopus laevis has been shown to be due to its rapid reduction and instantaneous re-oxidation which produces a reactive oxygen species, ROS. Nevertheless, PQ did not show any effects before hatching, stage 32, which showed a resistance, in early X. laevis development, to oxidative damage. Moreover, in view of its genotoxic properties in several experimental models, we studied PQ in the X. laevis cleavage phase that, characterized by a series of rapid mitotic divisions, might be damaged by genotoxic compounds. Embryos were exposed to 20, 40, 60, and 80 mg/l PQ concentrations from stage 2 to stage 9, and then left to develop in control FETAX solution until stage 47. The 80 mg/l PQ concentration gave 19% embryo mortality at the end of the exposure time, and 16.7% larvae mortality at the end of the test; both values were statistically different from the control, 5 and 6.8% respectively. These results confirmed the high resistance in early X. laevis development to PQ oxidative damage. The malformed larva percentages in the PQ exposed groups were higher as regards the control value but did not show any concentration-response; the most frequent malformed larvae found were affected by abnormal tail flexure coupled with abnormal gut coiling. A further experiment was carried out using the same methodology, but exposing embryos only to the 80 mg/l PQ concentration. The surviving blastulae were embedded in Paraplast, then the slides were stained with 4',6-diamidino-2-phenylindole (DAPI) and the nuclei were examined with a confocal microscope. This new preliminary procedure did not reveal any significant presence of micronucleated micromeres in PQ exposed blastulae with respect to the control. Nevertheless, the mechanism by which PQ induced abnormal tail flexure after cleavage exposure remained unknown. PQ seemed to pass through the jelly coats and vitelline membrane, but it expressed teratogenicity between the 2nd and 3rd day. PQ might be accumulated in the embryos during the exposure, and might express teratogenicity later, but it did not seem to induce genotoxicity during the cleavage phase of X. laevis even at very high concentrations.

Comparison between 1 year oral and transdermal oestradiol and sequential norethisterone acetate on circulating concentrations of leptin in postmenopausal women.

BACKGROUND: Oral and transdermal postmenopausal hormone replacement therapy (HRT) affects lipid and glucose metabolism differently, which is of significance in the release of leptin by adipocytes. Moreover, oestrogen and progesterone can stimulate leptin secretion in women of reproductive age. Therefore, we compared the effects of oral and transdermal oestrogen plus progestin regimen on plasma leptin in 38 healthy postmenopausal women with normal body mass index (BMI), who wished to use HRT to control incapacitating climacteric symptoms. METHODS: The women were randomized to treatment with oral HRT (2 mg oestradiol on days 1--12, 2 mg oestradiol plus 1 mg norethisterone acetate (NETA) on days 13--22, and 1 mg oestradiol on days 23--28, n = 19), or with transdermal HRT (50 microg/day of oestradiol on days 1--13, and 50 microg oestradiol plus 250 microg/day NETA on days 14--28, n = 19) for 1 year. Plasma samples were collected before and at oestradiol + NETA phase after 2, 6 and 12 months treatment and were assayed for leptin. RESULTS: The baseline leptin, ranging from 3.3 to 34.9 microg/l, was significantly associated with BMI (r = 0.78, P < 0.0001 ), but showed no difference between women in oral HRT (geometric mean 13.9 microg/l, 95% confidence interval (CI) 10.1--17.6 microg/l) or transdermal HRT group (geometric mean 12.0 microg/l, 95% CI 9.7--14.3 microg/l). Neither oral nor transdermal oestradiol + NETA caused any significant changes in plasma leptin (or BMI) after 2, 6, or 12 months of treatment. CONCLUSION: Leptin is an unsuitable factor to detect oestradiol + NETA-induced metabolic changes in postmenopausal women.

Vaginal clindamycin in preventing preterm birth and peripartal infections in asymptomatic women with bacterial vaginosis: a randomized, controlled trial.

OBJECTIVE: To determine whether treatment of bacterial vaginosis (BV) in early pregnancy decreases the risk of preterm delivery and peripartum infectious morbidity. METHODS: In this multicenter, randomized, double-masked, placebo-controlled intervention trial, screening for BV was performed by vaginal Gram stain obtained from 5432 healthy women with singleton pregnancies during the first antenatal clinic visit at 10--17 weeks' gestation. Bacterial vaginosis-positive women with no past history of preterm delivery were randomized to a single course of treatment with either 2% vaginal clindamycin cream or identical placebo cream for 7 days. Repeat Gram stains were taken 1 week after treatment and at 30--36 weeks' gestation. Preterm delivery was defined as spontaneous delivery before 37 gestational weeks. Peripartum infectious morbidity was defined as postpartum endometritis, postpartum sepsis, postcesarean wound infection, or episiotomy wound infection, necessitating antimicrobial therapy. According to the power analysis, 180 patients were needed for both treatment arms to show a three-fold difference in the rates of preterm births. RESULTS: The overall prevalence of BV was 10.4%. Of all BV-positive women, 375 (66%) were randomized to the treatment arms. The primary cure rate was 66% in the clindamycin group; in the placebo group, 34% spontaneously cleared BV (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.3, 2.8). The rate of preterm deliveries was 5% in the clindamycin group and 4% in the placebo group (OR 1.3, 95% CI 0.5, 3.5). The rate of peripartum infectious morbidity was 11% in the clindamycin group and 18% in the placebo group (OR 1.6, 95% CI 0.9, 2.8). Bacterial vaginosis recurred in 7% of women. The rate of preterm deliveries was 15% in this subgroup compared with 2% among women who remained BV negative (OR 9.3, 95% CI 1.6, 53.5). CONCLUSION: Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum infections, but recurrent or persistent BV increased the risk for these complications.

Transvaginal power Doppler findings in laparoscopically proven acute pelvic inflammatory disease.

OBJECTIVES: To evaluate the usefulness of power Doppler transvaginal sonography (TVS) in the diagnosis of pelvic inflammatory disease (PID) and to assess the diagnostic reliability of specific sonographic findings. POPULATION: The study population consisted of 30 women admitted for suspected acute PID. The reference group consisted of 20 women with proven hydrosalpinx formation. METHODS: Both conventional TVS and power Doppler TVS were performed. All patients with suspected acute PID underwent laparoscopy in order to confirm the diagnosis. Sonographic criteria described earlier were used for the diagnosis of acute PID. Power Doppler was used to assess the vascularity of any adnexal mass. RESULTS: Laparoscopy confirmed the diagnosis of PID in 20 (67%) of the 30 women with clinically suspected acute PID. Specific TVS findings, including wall thickness > 5 mm, cog-wheel sign, incomplete septa, and the presence of cul-de-sac fluid, discriminated women with acute PID from the control women with hydrosalpinx formation. Power Doppler TVS revealed hyperemia in all women with acute PID, but in only two women with hydrosalpinx (P = 0.01). Pulsatility indices were significantly lower in the acute PID group than in the control group (pulsatility index 0.84 +/- 0.04 vs. 1.50 +/- 0.10; P < 0.01). CONCLUSION: Power Doppler TVS was 100% sensitive and 80% specific in the diagnosis of PID (overall accuracy 93%). Specific sonographic landmark findings and power Doppler findings augment the clinical diagnosis of PID and allow simple classification of the severity of the disease.

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women.

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II-III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (+/-SD) follow-up time was 2.3 +/- 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 +/- 2.7 mm) to 6.8 +/- 4.2 mm at 6 months (P< 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment.

Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women.

OBJECTIVE: The aim of this study was to assess whether oral delivery and transdermal delivery of sequential combined hormone replacement therapy have similar effects on systemic blood pressure, as measured by 24-hour automated ambulatory recordings. STUDY DESIGN: Eighty-two healthy postmenopausal women, of whom 73 completed the study, were randomly assigned to start hormone replacement therapy with either orally (n = 38) or transdermally (n = 35) administered medication. Ambulatory blood pressure was recorded for a 24-hour period before the start of hormone replacement therapy and again 2 and 6 months later. Analysis of variance was used for data analysis. RESULTS: Hormone replacement therapy by both oral and transdermal routes was associated with slight but nonsignificant drops in mean 24-hour systolic and diastolic ambulatory blood pressure. Daytime systolic ambulatory blood pressure (mean +/- SE) fell significantly (P <.05) and similarly at 2 months in the oral (3.8 +/- 0.2 mm Hg) and transdermal (4.0 +/- 0.3 mm Hg) treatment groups. The daytime ambulatory blood pressure remained significantly lower than baseline at 6 months in the oral treatment group (-3.6 +/- 0.3 mm Hg), whereas the fall at 6 months in the transdermal group (-3.1 +/- 0.3 mm Hg) was not significant. Mean daytime diastolic ambulatory blood pressure was reduced in both the oral (-1.8 +/- 0.8 mm Hg) and transdermal (-3.5 +/- 0.7 mm Hg; P <.05) treatment groups at 2 months but not at 6 months. Nighttime ambulatory blood pressures in both groups remained unaffected by hormone replacement therapy. CONCLUSION: Sequential combined hormone replacement therapy delivered by both oral and transdermal routes caused significant falls in the daytime ambulatory blood pressure of normotensive postmenopausal women at 2 months of treatment. This fall persisted as long as 6 months of treatment in the oral treatment group but not in the transdermal treatment group.

Uterine artery impedance to blood flow on the day of embryo transfer does not predict obstetric outcome.

OBJECTIVE: To evaluate the influence of uterine artery impedance to blood flow on the day of embryo transfer for prediction of early pregnancy loss and obstetric outcome. METHODS: The uterine artery pulsatility index (PI) and resistance index (RI) were evaluated prospectively by transvaginal Doppler in 102 infertile women, who conceived as the result of fresh or frozen embryo transfer. Uterine artery impedance to blood flow was compared to the obstetric outcome. RESULTS: The 111 treatment cycles studied resulted in 31 spontaneous abortions, four ectopic pregnancies, and 76 deliveries. There were no differences in uterine artery PI and RI (mean +/- SD) between cycles resulting in normal delivery (2.69 +/- 0.71 and 0.88 +/- 0.06) and those resulting in spontaneous abortion (2.71 +/- 0.67 and 0.88 +/- 0.05) or ectopic pregnancy (2.36 +/- 0.54 and 0.85 +/- 0.06). There were no differences in PI and RI between uncomplicated singleton pregnancies (2.74 +/- 0.78 and 0.88 +/- 0.06) and those developing intra-uterine growth restriction (IUGR), pregnancy-induced hypertension (PIH), or preterm birth (2.54 +/- 0.47 and 0.87 +/- 0.04, pooled data). CONCLUSIONS: Uterine artery PI and RI on the day of embryo transfer were unrelated to the risk of the pregnancy ending in spontaneous abortion or ectopic pregnancy. These values were of no value in the prediction of IUGR, PIH or preterm birth.

Laparoscopic management of suspected acute pelvic inflammatory disease.

STUDY OBJECTIVE: To evaluate the efficacy of acute-phase operative laparoscopy in women with suspected pelvic inflammatory disease (PID). DESIGN: Open series (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Thirty-three patients with clinically suspected PID. INTERVENTION: Acute-phase operative laparoscopy. MEASUREMENTS AND MAIN RESULTS: Laparoscopy confirmed the diagnosis of PID in 20 (61%) patients; 11 (33%) women had other disease and 2 (6%) had no evidence of disease. Laparoscopic procedures in women with PID were pelvic irrigation (all patients), lysis of adhesions (most cases), drainage and irrigation of unilateral or bilateral pyosalpinx (7), drainage and irrigation of tubo-ovarian abscess (3), and extirpation of disease (2). Laparoscopic intervention was also performed in 11 (85%) of 13 women without PID. No major complications occurred. CONCLUSION: Acute-phase operative laparoscopy provided a final diagnosis in all but three patients (91%).

Short-term metabolic effects of isradipine and metoprolol in pre-eclampsia.

OBJECTIVE: To study the effects of isradipine or metoprolol on insulin sensitivity and lipid profiles as well as on blood pressure and umbilical vascular resistance in pre-eclamptic women in the third trimester of pregnancy. DESIGN: A single-centre, prospective, randomized, double-blind, double-dummy and parallel-group study. SETTING: Helsinki University Central Hospital, a tertiary referral centre. PATIENTS: Twenty-four previously healthy pregnant women with normal findings in an oral glucose-tolerance test who were hospitalized for preeclampsia, of whom 17 completed the study. INTERVENTIONS: Between 29 and 39 weeks of gestation, measurements were made of insulin sensitivity (the minimal model), magnitude of proteinuria, and the fasting levels of serum uric acid, lipids and lipoproteins. Subsequently, treatment with isradipine 2.5 mg (n = 9) or metoprolol 50 mg (n = 8) twice daily was started, and these women were reinvestigated 5-7 days later. Blood pressure was recorded during 24 h by automated ambulatory blood pressure measurement. Umbilical artery resistance index was measured by Doppler ultrasound. MAIN OUTCOME MEASURES: Insulin sensitivity, uric acid, degree of proteinuria, lipids and lipoproteins, blood pressure, umbilical artery resistance index. sensitivity, degree of proteinuria, blood pressure, or the umbilical artery resistance index. Serum uric acid increased in both groups (P<0.05). High-density lipoprotein2 cholesterol increased 15.6% in the isradipine group (P<0.05), but no significant changes appeared in other lipids and lipoproteins in either group. CONCLUSIONS: In this study, short-term antihypertensive treatment with isradipine or metoprolol in preeclampsia had no detrimental effect on serum lipid and lipoprotein levels or insulin sensitivity.

Menorrhagia and uterine artery blood flow.

Menorrhagia is a significant problem in women of reproductive age. In half of the cases no specific aetiology is known. Vascular factors play a role but remain poorly understood. We chose to study whether any association exists between the flow impedance of uterine arteries and the amount of menstrual blood loss. The study population consisted of 60 spontaneously menstruating 35- to 49-year-old women without endometrial hyperplasia, polyps, or submucous fibroids. The pulsatility index (PI) from uterine arteries, arcuate arteries, and radial arteries was measured by transvaginal colour Doppler. Menstrual blood loss was measured by the alkaline haematin method. A significant inverse correlation was found between uterine artery PI and the amount of menstrual blood loss, suggesting that women with lower uterine flow impedance bleed more. A regression model confirmed that this association was specific and not explained by uterine size, fibroids or any other of the 11 potential confounders included in the model. The correlation between uterine artery PI and amount of menstrual blood loss suggests that vascular factors may be involved in the pathogenesis of menorrhagia.

Randomized comparison of oral and transdermal hormone replacement on carotid and uterine artery resistance to blood flow.

OBJECTIVE: To compare the long-term effects of oral and transdermal hormone replacement therapy (HRT) on carotid and uterine vascular impedance. METHODS: Sixty-three postmenopausal women were randomized to 1 year's treatment with oral or transdermal sequential combined HRT. Carotid and uterine artery pulsatility indices (PIs) were assessed by color Doppler at baseline, and after 2, 6, and 12 months of treatment. Fifty-eight women completed the trial, 27 in the oral and 31 in the transdermal group. In a subgroup of 30 women, we also performed Doppler measurements in the estrogen-progestin combined phase. The study had 90% power to detect a difference between treatment groups of 0.05 in the carotid artery and of 0.25 in uterine artery PI at the 5% significance level. RESULTS: The carotid PI decreased significantly (P < .001) and similarly during both regimens. This drop was already clearly detectable during the second month, from 0.97 (0.95, 1.01) (mean and 95% confidence intervals [CII) to 0.94 (0.91, 0.97) in the oral and from 0.98 (0.94, 1.00) to 0.92 (0.89, 0.95) in the transdermal group, but it continued up to 12 months (0.85 [0.82, 0.88], 13% of baseline values in the oral group and 0.84 [0.81, 0.871, 14% in the transdermal group). In the uterine arteries, the drop in PI was steeper and greater and reached its maximum at 6 months (39% and 40%, respectively). Drops in carotid and uterine PI correlated positively with baseline PI values, but were not affected by patient age, time from menopause, previous HRT and smoking. Addition of norethisterone acetate did not counteract drops in carotid and uterine PI in either group. CONCLUSION: Oral and transdermal sequential HRT are similarly effective at 1 year in reducing impedance to flow in carotid and uterine circulation. This long-term vascular effect might explain how HRT protects women from cardiovascular disease.

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation.

OBJECTIVE: We studied whether transdermal nitroglycerin, a donor of nitric oxide, affects uterine, umbilical, and fetal cerebral blood flow in pregnancies complicated by preeclampsia and impaired uteroplacental blood flow. STUDY DESIGN: Seventeen patients with preeclampsia were treated with a nitroglycerin patch, 10 mg per 24 hours, for three consecutive days between 28 and 36 weeks' gestation. The uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index were assessed by color Doppler ultrasonography before the start of treatment, daily during treatment, and on the first 2 days after the removal of the last patch. RESULTS: The nitroglycerin patch caused a significant fall in the mean uterine pulsatility index and resistance index that reached its maximum (18% +/- 4% and 17% +/- 3%, respectively, from baseline) on the last treatment day. After the removal of the last patch, uterine pulsatility index and resistance index rose to the pretreatment value within 12 hours. No significant changes in umbilical or middle cerebral artery pulsatility index and resistance index were observed during treatment. Maternal mean arterial pressure fell from 122 +/- 8 to 117 +/- 7 mm Hg (P = .05). CONCLUSION: Transdermal administration of nitroglycerin may offer a potential for treatment for patients with preeclampsia who have increased uteroplacental impedance.

The long-term effects of oral and transdermal postmenopausal hormone replacement therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane.

OBJECTIVE: Oral postmenopausal hormone replacement therapy (HRT) decreases the risk of cardiovascular disorders, but the mechanisms of this protection are largely unknown. We compared the long-term effects of sequential oral HRT and transdermal HRT on vasodilatory nitric oxide and prostacyclin as well as vasoconstrictive endothelin- and thromboxane A2, all of which may be factors in the protective effect of HRT against cardiovascular disorders. DESIGN: Prospective, randomized study. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Fifty-two healthy postmenopausal female nonsmokers (n = 42) or smokers (n = 10) who had climacteric symptoms. INTERVENTION(S): The women received either oral HRT (2 mg of estradiol on days 1-12, 2 mg of estradiol plus 1 mg of norethisterone acetate on days 13-22, and 1 mg of estradiol on days 23-28; n = 21) or transdermal HRT (50 microg/d of estradiol on days 1-28 followed by 250 microg/d of norethisterone acetate on days 14-28; n = 21) for 1 year. Ten female smokers received transdermal HRT for 1 year. MAIN OUTCOME MEASURE(S): Plasma levels of nitrate as an index of nitric oxide production, endothelin-1, and urinary output of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha) and that of the thromboxane A2 metabolite (2,3-dinorthromboxane B2) were measured before and during the combined phases of the 2nd, 6th, and 12th treatment months. RESULT(S): Both regimens increased plasma estradiol levels and alleviated vasomotor symptoms. Neither regimen caused significant changes in nitrate, endothelin-1, prostacyclin, or thromboxane A2 in nonsmoking women. Female smokers had significantly higher levels of endothelin-1, which were significantly reduced by transdermal HRT at 6 months of treatment. CONCLUSION(S): Nitric oxide, endothelin-1, prostacyclin, and thromboxane A2 are not of primary importance in the protective effect of sequential oral HRT against cardiovascular disorders in otherwise healthy nonsmoking postmenopausal women. In this regard, transdermal HRT appears comparable to oral HRT. Postmenopausal female smokers have high levels of endothelin-1 that are reduced by transdermal HRT.