Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: an observational study.

PURPOSE OF INVESTIGATION: To evaluate the effect of soy isoflavones and inulin (SII) on hot flushes (HF) and quality of life in a clinical setting, the authors conducted an observational study. MATERIALS AND METHODS: The authors performed an observational, prospective, multicentric study on women in peri-/post-menopause treated or untreated with a product present on the Italian market, consisting in a mixture of calcium (500 mg), vitamin D3 (300 IU), inulin (3 g) and soy isoflavones (40 mg). RESULTS: A total of 135 patients, 75 (55.6%) in the SII group and 60 (44.4%) in the untreated group entered the study. After three months, the mean number of HF declined of 2.8 (SD 3.7) in the SII group and 0.0 in the untreated one. The corresponding values after six months were -3.7 (SD 2.7) in the SII group and -0.9 (SD 5.3) in the control group (p = 0.02). CONCLUSION: This observational trial suggests a possible beneficial effect of a dietary soy supplement containing 40 mg of isoflavone/day plus inulin in the management of menopausal symptoms such as hot flashes.

Uterine leiomyosarcoma: report of three cases and review of the literature.

This is the report of three cases of unsuspected uterine leiomyosarcoma diagnosed by pathologist after hysteroscopic resection. The literature on this issue has been reviewed. Mesenchymal uterine tumors are rare malignancies, occurring in only 17 per one million women annually. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma, and malignant mixed Müllerian tumour. Less than one percent of women believed to have a leiomyoma actually have a sarcoma at hysterectomy. According to the authors' experience and the available literature reviewed, the removal of the whole myomatosus lesion, even if its appearance suggests a typical submucosal myoma, represents the only method to definitively rule out the presence of sarcomatous tissue.

Frequency of human papillomavirus infection and genotype distribution among women with known cytological diagnosis in a Southern Italian region.

INTRODUCTION: In the Puglia region (South Italy) about 200 new hospitalizations for cervical cancer are registered every year. The study investigated the frequency of Human Papillomavirus (HPV) infection and the genotype distribution of HPV in a sample of women with known cytology attending the outpatient clinics of four Gynecological Departments of the University of Bari over a four-year period (2005-2008). METHODS: Cervical samples from 1,168 women were analyzed for the presence of HPV-DNA through Polymerase Chain Reaction (PCR) in L1 region and reverse hybridization. The cytological results were associated with HPV positivity and type-specific prevalence. RESULTS: Overall, HPV infection was found in 355 (30.4%) women. HPV-DNA was found in 34.4% of women with a cytological diagnosis of ASCUS, in 46.8% of women with Low-grade Squamous Intraepithelial Lesion (LSIL) and in 87.0% of women with High-grade Squamous Intraepithelial Lesion (HSIL)/carcinoma. Also 16.0% of women with normal Pap smear were found to be HPV-DNA positive. The most common HPVgenotype was type 16 found in 27.3% of positives, followed by type 53 (11.5%), type 66 (9.2%) and type 31 (9.0%). HPV genotype 18 was found in 6.4% of positives. Types 16 or 18 were detected in about 34% (120/355) of all infected women, in about 33% of LSIL and in 60% of HSIL/ carcinoma HPV-positive women. Among low risk (LR) genotypes, type 61 was found in 10.7% of HPV positive women, type 62 in 8.4%, type 42 in 8.1% and type CP6108 in 7.8%. DISCUSSION AND CONCLUSIONS: The findings of the study give evidence that HPV infection is frequent in the studied cohort of women. The most widespread genotypes found were 16 and 53. These data may represent a benchmark for future evaluation after the recent introduction of vaccination against HPV in 12-year-old girls.

[Reliability of the diagnostic fluid mini-hysteroscopy in the diagnosis of intrauterine pathologies]. / Affidabilità della mini-isteroscopia diagnostica a liquido per la diagnosi delle patologie intrauterine.

AIM: The aim of this study was to determine the diagnostic accuracy of minihysteroscopy with fluid distention and vaginoscopic approach for the diagnosis of endometrial pathologies. METHODS: This controlled clinical study was conducted on 930 women with endometrial abnormalities who referred to our Department of Obstetrics and Gynecology, University Medical School of Bari, to perform hysterectomy. One week before hysterectomy all the patients underwent minihysteroscopy with fluid distention. Histological diagnoses were compared with the hysteroscopic findings, and the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were determined. RESULTS: Hysteroscopy was technically successful in all women and revealed sensitivity of 98%, specificity of 99%, a positive predictive value of 92%, a negative predictive value of 99%, and diagnostic accuracy of 99% for the diagnosis of endometrial carcinoma. CONCLUSIONS: Size reduction of the hysteroscope is of greatest importance for reducing pain and risk of vasovagal reaction. In conclusion, the best approach in terms of ease, reliability, acceptability, and safety to patients in whom intrauterine exploration is indicated should be simple diagnostic mini-hysteroscopy using a small-diameter, rod lens hysteroscope with a single-flow diagnostic sheath, vaginoscopic approach, and fluid distention. In this way in about 90% of patients, a correct diagnosis and proper choice for eventual subsequent operative strategy can be obtained, without discomfort and risk.

Pro-inflammatory M1/Th1 type immune network and increased expression of TSG-6 in the eutopic endometrium from women with endometriosis.

OBJECTIVE: The study aimed to explore the type 1 and type 2 cytokines expression in the endometrium from women affected by endometriosis compared to controls. The expression of TSG-6, a multifunctional protein involved in several inflammatory disease, was also evaluated. Study Design SETTING: Experimental clinical study. PATIENTS: 10 patients affected by endometriosis and 11 controls. INTERVENTIONS: Patients underwent to an ultrasound transvaginal examination and a diagnostic hysteroscopy in order to exclude any uterine abnormality. All patients underwent endometrial biopsy using a Novak's curette. MAIN OUTCOME MEASURES: The endometrial expression of type 1 (IL- 1 ß TNF-α, IL-8) and type 2 (IL-10) cytokines, and of TSG-6 was evaluated by immunohistochemistry and by real time PCR. The expression of TSG-6 was confirmed by western blot. RESULTS: Results of PCR analysis and of immunohistochemistry revealed an increased expression of IL-1ß, TNF-α, IL-8 and of TSG-6 in the endometrium of endometriosic patients. IL-10 expression did not show any difference. CONCLUSIONS: An increased expression of pro-inflammatory type 1 cytokines was demonstrated in the endometrium from endometriosic patients, suggesting an endometrial environment harmful for implantation due to the prevalence of Th1 related immunity. An increased expression of TSG-6 was also demonstrated for the first time. Our findings concur to better define the inflammatory imbalance and the abnormal endometrial receptivity, reported in literature, of the eutopic endometrium of women affected by endometriosis.

2D and 3D Ultrasonographic Evaluation of Fetal Midface Hypoplasia in Two Cases with 3-M Syndrome.

This paper highlights the utility of 2D and 3D ultrasonography in the prenatal diagnosis of facial dysmorphisms suggestive of very rare syndromes such as 3-M syndrome. Two pregnant women at risk for fetal skeletal dysplasias were referred to our clinic for 2D/3D ultrasound scan in the second trimester of pregnancy. Only one of the patients had a familial history of 3-M syndrome. Karyotyping and genetic testing of abortion material were performed in both cases. 2D ultrasonography revealed growth retardation of the long bones in both cases. In the case without a familial history of the syndrome, 2D and 3D ultrasonography showed an absence of nasal bones and a flat malar region suggestive of 3-M syndrome, although the difficult differential diagnosis included other dysmorphic growth disorders with prenatal onset. The karyotype was normal but the pregnancy was terminated in both cases. Postmortem examination confirmed 3-M syndrome as indicated by prenatal findings. In high-risk cases with a familial history of 3-M syndrome, prenatal diagnosis of 3-M syndrome is possible by analyzing fetal DNA. In the absence of risk, a definitive prenatal diagnosis is often not possible but may be suspected in the presence of shortened long bones, normal head size and typical flattened malar region (midface hypoplasia) shown on complementary 2D and 3D sonograms. 2D and 3D ultrasonography has been shown to offer reliable information for the prenatal study of skeletal and facial anomalies and can be useful if there is a suspicion of 3-M syndrome in a pregnancy not known to be at risk.

[Urinary incontinence in postmenopausal period: clinical and pharmacological treatments]. / Incontinenza urinaria in menopausa: trattementi clinici e farmacologici.

Urinary incontinence is a common clinical problem in female sex and occurs especially in postmenopausal women; this disease, that represents an economical problem for society, begins in young age, arises in middle age and increases in women more than 65 years old. Studies carried out on etiological factors involved in urinary incontinence show that estrogens enhance the trophism and vascularization of the muscular and fascial support of the pelvic floor, the growth of fibroblasts and the collagen metabolism in the superficial fascia in postmenopausal women. The postmenopausal estrogenic deficit could be related to many urogenital problems, but many researches performed on the effects of estrogens in urogenital postmenopausal homeostasis and of hormonal replacement therapy in postmenopausal incontinent women, did not show conclusive findings; for this reason, even if many authors attributed to menopause a role of major risk factor for incontinence, a direct correlation has never been confirmed. The treatment of postmenopausal female incontinence may be clinical and pharmacological, and includes a first step therapy (bladder training, biofeedback techniques, electrical pelvic floor stimulation) and a second step therapy (pharmacological therapy, bladder devices and surgical operations). In this review the clinical and pharmacological treatments, their efficacy and their application in incontinent postmenopausal women are described.

Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy.

Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P < 0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P < 0.05). In conclusion, patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.

Transabdominal sonohysterography, transvaginal sonography, and hysteroscopy in the evaluation of submucous myomas.

OBJECTIVE: To assess the usefulness of transabdominal sonohysterography in the diagnosis and evaluation of submucous myomas. METHODS: Fifty-two premenopausal women hospitalized for hysterectomy for benign gynecologic indications underwent preoperative conventional transvaginal sonography, transabdominal sonohysterography, and hysteroscopy. The results of the three techniques in terms of diagnosis, size, intracavitary growth, and location of the submucous myomas were compared with those revealed by direct inspection of the surgical specimens. RESULTS: Conventional transvaginal sonography for the diagnosis of submucous myomas had a sensitivity of 90% and a specificity of 98%; the predictive values of abnormal and normal scans were 90 and 98%, respectively. Transabdominal sonohysterography had sensitivity, specificity, and predictive values of 100%, as did hysteroscopy. In all cases, the sonographic techniques measured tumor size more accurately than did hysteroscopy. The transabdominal sonohysterography measurements differed from direct evaluation by no more than 2 mm, and the hysteroscopic measurements were significantly different from those of the surgical specimens. The sonohysterographic evaluation of intrauterine growth was significantly more precise than that of the other techniques, differing from direct measurements by no more than 5-10%. Conventional transvaginal sonography failed to localize three of 11 myomas; hysteroscopy and transabdominal sonohysterography provided the exact location in all cases. CONCLUSION: Transabdominal sonohysterography is the most accurate technique for detecting submucous myomas and evaluating their size, intracavitary growth, and location.

Direct transport of progesterone from vagina to uterus.

OBJECTIVE: To compare progesterone concentrations in serum and endometrial tissue from hysterectomy specimens after vaginal or intramuscular (IM) administration of progesterone gel. METHODS: This was a randomized open study of 14 post-menopausal women undergoing transabdominal hysterectomies. Participants received either vaginal progesterone gel, 90 mg, or IM progesterone, 50 mg, at 8:00 AM and 8:00 PM on the day before surgery and at 6:00 AM on the day of surgery. Venous blood samples for progesterone measurement were collected at 8:00 AM on the day before surgery (baseline) and during surgery. After removal of the uterus, the endometrium was sampled from the anterior and posterior walls. Results were expressed as ratios of endometrial to serum progesterone concentrations x 100. RESULTS: Ratios of endometrial to serum progesterone concentrations were markedly higher in women who received vaginal progesterone (14.1 median, 8.5-59.4 range; 95% confidence interval [CI] 9.89, 38.79) compared with IM injections (1.2 median, 0.5-13.1 range; 95% CI -0.48, 7.39) (P < .005). CONCLUSION: Ratios of endometrial to serum progesterone concentrations were higher after vaginal administration of progesterone than after IM injections. Our findings in endometrial tissue specimens from hysterectomies excluded the possibility of contamination by progesterone that remained in the vagina.

Ontogenesis of autonomic receptors in detrusor muscle and bladder sphincter of human fetus.

An investigation was made of the distribution and the ontogenesis of various types of receptors in the bladder detrusor muscles and sphincter isolated from human fetuses at different stages of pregnancy. Cholinergic receptors appear very early in the fetal urinary bladder since contractile responses to bethanechol, competitively blocked by atropine, are observed in detrusor muscle preparations at three months and in the sphincter at four months. Later on, the density of cholinergic receptors increases in the detrusor muscle whereas there is a progressive reduction in the sphincter.

Effects of the repetitive administration of progesterone by nasal spray in postmenopausal women.

OBJECTIVE: To study the effects of 10 days of nasal spray P treatment on P serum levels and the endometrium. DESIGN: Prospective. SETTING: University Medical School. PATIENTS: Eight postmenopausal women received oral conjugated estrogens at a daily dose of 0.625 mg for 4 weeks immediately before vaginal surgery for prolapse. For the first 9 of the last 10 days the patients also received a nasal spray dosage of 11.2 mg P three times a day; on the 10th day they received only one dose. MAIN OUTCOME MEASURES: Blood samples were taken at 8:00 A.M. on treatment days 1, 3, 5, 7, 10, and 11 to follow P serum concentration levels. Endometrial samples for histologic examination were collected before P administration and immediately after surgery to evaluate the end-organ effect. RESULTS: Mean P serum levels increased sixfold after 9 days of nasal spray P administration [from 0.612 +/- 0.280 ng/mL (1.958 +/- 0.896 nmol/L) to 3.925 +/- 1.553 ng/mL (12.560 +/- 4.970 nmol/L)] and declined thereafter, returning to the before treatment levels 24 hours after the last administration. In all subjects, the first histologic evaluation showed proliferative endometrium; the second showed clear secretive changes. CONCLUSIONS: Repetitive nasal spray P administration for 10 days in postmenopausal women led to increasing P serum levels and, when the estrogen stimulation was adequate, to secretory changes in the endometrium (end-organ effect).

Progesterone administration by nasal spray.

The bioavailability and the clinical usefulness of the P administered by nasal spray were investigated. Ten healthy menopausal women received an IN spray administration (4 doses of an oleic P solution 20 mg/mL, corresponding to nearly 11.2 mg of P) and the circulating P levels were calculated. Sixty minutes after administration, the maximum concentration (CMax, 3.75 +/- 0.214 ng/mL) was reached. High P levels (greater than 2 ng/mL) lasted until 360 minutes, and the AUC 0 to 720 was 1,481.6 +/- 343 ng.h/mL. Progesterone administration by spray formulation has proven to be effective in reaching therapeutic levels and to be acceptable to patients and, probably, clinically safe.

PIP: The bioavailability of progesterone administered by a nasal dose was investigated in 10 healthy menopausal women (average age. 56.4 years). Each woman received 2 spray doses per nostril, for a total progesterone dosage of 11.2 mg. Physiological circulating progesterone levels (greater than 2 ng/mL) were achieved within 2 minutes after intranasal spray administration, lasted an average of 6 hours, and returned to baseline values after 12 hours. The highest mean circulating level of progesterone was achieved at 60 minutes (3.750 + or - 0.214 ng/mL) and a secondary peak was recorded at 240 minutes (2.700 + or - 0.244 ng/mL). Variability in circulating levels of progesterone after spray administration did not exceed 34% in any patient until the final measurement point (720 minutes). There was no evidence of nasal irritation, but all subjects complained of the unpleasant taste of the spray. The effectiveness of intranasally administered progesterone appears due to progesterone's high solubility in the oleic carrier and the wide surface of the nasal mucosa covered by the nebulized solution. Considering the liver first-pass metabolic effect when progesterone is administered orally and the insufficient bioavailability of progesterone produced by rectal or vaginal administration, further investigation of the nasal spray approach is urged.

Circulating levels of nitric oxide in fertile women in relation to the menstrual cycle.

OBJECTIVE: To investigate nitric oxide (NO) production in the two phases of normal menstrual cycle. DESIGN: Prospective clinical study. SETTING: Normal human volunteers in an academic research environment. PATIENT(S): Fifteen normally cycling women. INTERVENTION(S): Follicle growth monitoring by ultrasound, serum, and plasma sampling in the midfollicular phase, at ovulation, and in the midsecretory phase. MAIN OUTCOME MEASURE(S): Plasma concentration of NO stable oxidation products and serum concentrations of E2 and P. RESULT(S): Plasma concentration of NO metabolites resulted higher in the follicular phase with respect to the secretory phase and peaked at midcycle. CONCLUSION(S): The results strongly support the existence of an E2 control of NO production and release. The significant reduction in NO metabolites observed in the secretory phase suggests a possible opposing action of P on either NO production or release.

Acute effects of transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To investigate the acute effects of transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: Normal human volunteers in an academic research environment. PATIENT(S): Twenty healthy postmenopausal women. INTERVENTION(S): Transdermal administration of 100 micrograms/d E2 or placebo. MAIN OUTCOME MEASURE(S): Plasma concentrations of NO stable oxidation products and serum concentrations of E2 were assessed before and 24 hours after the administration. RESULT(S): In the group treated with E2 mean concentration of NO metabolites 24 hours after patch application (37.31 +/- 7.62 mumol/L) resulted significantly higher than baseline (21.04 +/- 5.71 mumol/L) and the control group (23.50 +/- 4.03 mumol/L). The correlation between the mean percent increase in NO metabolites and absolute E2 concentrations 24 hours after the E2 administration was statistically significant. CONCLUSION(S): Transdermal administration of E2 to healthy postmenopausal women increases the plasma levels of NO and this supports the hypothesis that a NO-related mechanisms may contribute to the cardiovascular protective effect of estrogens in postmenopause.

Resectoscopic treatment of uterus didelphys with unilateral imperforate vagina complicated by hematocolpos and hematometra: case report.

OBJECTIVE: To describe a technique for treating hematocolpos and hematometra in patients with uterus didelphys and unilateral imperforate vagina involving the use of resectoscopy under ultrasonographic control. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 13-year-old girl with uterus didelphys with unilateral hematometra, hematocolpos, and ipsilateral renal agenesis. The girl complained of severe abdominal pain, which appeared with each of her menses. INTERVENTION(S): The intervention was performed by a vaginoscopic approach to preserve the integrity of the hymen. The first incision on the vaginal wall was performed in correspondence with the hematocolpos under continuous ultrasonographic guidance with the use of a straight resectoscopic loop. Resection of the vaginal septum was continued with the use of an angled resectoscopic loop until almost complete excision of the septum was achieved. MAIN OUTCOME MEASURE(S): Clinical, echographic, and vaginoscopic findings before the operation and 2 and 6 months after the operation. RESULT(S): The surgical procedure was easy to perform. Almost complete excision of the septum was achieved with just a few passages of the resectoscope. Complete drainage of both the hematocolpos and the hematometra was confirmed by ultrasonography. The postoperative period was completely uneventful. Clinical and vaginoscopic evaluations 6 months after the operation confirmed the integrity of the hymen, the complete resolution of clinical symptoms, and the persistence of a large communication between the two vaginas. CONCLUSION(S): Resectoscopic excision under ultrasonographic guidance of the vaginal septum in a girl with uterus didelphys with unilateral hematometra and hematocolpos was effective and easy to perform, and it fully respected the integrity of the reproductive system.

Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women.

OBJECTIVE: To verify the occurrence of preferential distribution of vaginally administered progesterone to the uterus compared with extrapelvic regions in vivo and in humans. DESIGN: Prospective clinical study. SETTING: University medical school. PATIENT(S): Twenty postmenopausal women undergoing transabdominal hysterectomy for benign pathologies. INTERVENTION(S): Forty-five minutes before surgery, the women received a single vaginal administration of an oil-based micronized progesterone (100 mg) solution currently available on the market for IM use. During the operation, parallel blood samples were drawn from the uterine and radial arteries. MAIN OUTCOME MEASURE(S): Plasma levels of progesterone were measured by RIA. RESULT(S): Mean (+/- SD) plasma levels of progesterone were significantly higher in the uterine artery than in the radial artery (9.75 +/- 3.21 vs. 5.12 +/- 2.06 ng/mL, respectively). CONCLUSION(S): Vaginal administration allows a preferential distribution of progesterone to the uterus, which confirms the existence of the so-called "first uterine pass effect."

Pharmacokinetics and endometrial effects of the vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women.

OBJECTIVE: To study the pharmacokinetics of the transvaginal absorption of 100 mg micronized P from an oil-based solution in postmenopausal women before and after the estrogenization of the vaginal mucosa and to evaluate the endometrial effects of 10 days of once daily P vaginal administration. DESIGN: Prospective clinical trial. SETTING: University Medical School. PATIENTS: Nine postmenopausal women undergoing hormone replacement therapy. INTERVENTIONS: A micronized P (100 mg) oil-based solution currently available on the market for IM use was administered vaginally by means of a Teflon cannula without the aid of a speculum. Subsequently, the women received 4 weeks 0.1 mg/d transdermal E2 treatment combined on the last 10 days with the once daily vaginal administration of P in the same way as before. MAIN OUTCOME MEASURES: At the first (before estrogen) and second (during estrogen therapy) P administrations, P serum levels were measured at time 0, and then after 15, 30, 45, 60, 120, 240, 480, and 1440 minutes. Endometrial samples were collected at the end of treatment. RESULTS: After the first administration, a mean Cmax of 5.40 +/- 0.92 ng/mL (mean +/- SD) was reached at a Tmax of 45 minutes (range 30 to 480 minutes). The serum concentrations returned to their initial values after 24 hours. The second P administration reached a mean Cmax of 5.30 +/- 1.04 ng/mL at a Tmax of 60 minutes (range 30 to 240 minutes); after 24 hours, the serum P levels still were significantly higher than at baseline and at the same time after the first administration. None of the women complained of significant vaginal losses. No signs of vaginal phlogosis or irritation were observed. In all subjects, histologic evaluation showed clear endometrial secretory changes. CONCLUSIONS: The daily vaginal administration of one vial of micronized P for 10 days allowed useful serum P levels to be reached, especially after estrogen therapy, and induced clear secretory changes in the endometrium.

Effects of short-term transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women.

OBJECTIVE: To assess the effects of short-term transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Twenty-eight healthy postmenopausal women. INTERVENTION(S): Transdermal administration of E2 (100 microg/d) or placebo on days 1 and 4 of a 1-week treatment regimen. MAIN OUTCOME MEASURE(S): Serum concentrations of E2 and plasma concentrations of NO stable oxidation products were assessed on day 1, before placement of the patch, and subsequently on days 2, 3, and 6. RESULT(S): The mean concentration of NO metabolites on days 2, 3, and 6 was significantly greater in the E2 group (40.08+/-15.42 micromol/L, 38.05+/-18.82 micromol/L, and 42.03+/-16.81 micromol/L on days 2, 3, and 6, respectively) compared with both baseline levels (23.07+/-5.79 micromol/L) and the placebo group (23.51+/-4.06 micromol/L, 21.64+/-4.72 micromol/L, and 21.81+/-4.46 micromol/L on days 2, 3, and 6, respectively). CONCLUSION(S): During a 1-week treatment regimen with transdermal E2, plasma levels of NO in postmenopausal women were significantly higher than baseline levels on days 2, 3, and 6. This suggests that the effect of estrogens on NO synthesis is rapid and that it is maintained with repeated administration.

Tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy and minihysteroscopy) versus hysterosalpingography in an outpatient infertility investigation.

OBJECTIVE: To compare the acceptance and tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy [THL] combined with minihysteroscopy) versus hysterosalpingography (HSG) for evaluating tubal patency and the uterine cavity in an outpatient infertility investigation. DESIGN: Randomized controlled study. SETTING: University hospital. PATIENT(S): Twenty-three infertile patients without obvious pelvic pathology. INTERVENTION(S): Women were randomly divided into two groups. One group underwent minihysteroscopy and THL with tube chromoperturbation as first investigation and HSG within the following 7 days, while in the other group the investigation sequence was inverted. Women reported pain experienced before and at the end of procedures. MAIN OUTCOME MEASURE(S): Mean duration of procedures, level of pain experienced, diagnostic agreement about tubal patency and uterine cavity normality. RESULT(S): THL and minihysteroscopy took significantly more time but was significantly less painful than HSG. Regarding tubal patency, in 95.5% of cases THL agreed with HSG. In one case, HSG diagnosed a bilateral obstruction of tubes, whereas at THL a bilateral spreading of methylene blue was seen. Agreement on intrauterine pathologies between minihysteroscopy and HSG was poor (43%); the number of intrauterine abnormalities found at hysteroscopy was significantly greater than at HSG. CONCLUSION(S): THL in association with minihysteroscopy provided more information and was better tolerated than HSG in an outpatient infertility investigation.