Moderate and severe fetal pyelectasis: Correlation between prenatal aspects and postnatal outcome.

BACKGROUND: Renal pelvic dilatation (RPD) is a frequent finding in fetal ultrasound. The aim of the study is to correlate the prenatally detected moderate and severe pyelectasis with the postnatal outcome. METHODS: A retrospective analysis involving 90 cases of prenatally detected moderate and severe RPD referred to our prenatal diagnosis centre with 18 months of urological follow-up. Prenatal ultrasound was correlated with postnatal renal function, assessed by plasmatic creatinine and/or renal scintigraphy performed before surgery. RESULTS: Cases were divided between two groups according to postnatal management: group A including 35 newborns (38.9%) that needed surgical treatment and group B with 55 patients (61.1%) who were managed conservatively. The group A presented higher median RPD (18 mm, IQR 12-25 mm) compared to the group B (11 mm, IQR 10-14 mm). The most common anomaly detected within group A was pelvi-ureteric junction (PUI) obstruction (43%). Within group B 32 cases (58%) showed spontaneous resolution of hydronephrosis during postnatal follow up. In case of moderate pyelectasis the risk of postnatal surgery was 25% and raised to 60% for severe RPD. In our study, 29 newborns showed pathologic scintigraphies: 25 required surgery while 4 did not find indication for surgery due to ipsilateral renal function irreversible damage. 6 patients had high creatinine level (>0.6 mg/dl). 35 cases out of 90 (39%) developed monolateral irreversible renal function impairment. CONCLUSION: Moderate and severe RPD are often correlated with postnatal renal damage, therefore a close multidisciplinary follow-up is required. Prenatal scanning is highly predictive of postnatal outcome and can address properly the prenatal counseling.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Effects of recombinant follicle-stimulating hormone on bone turnover markers in infertile women undergoing in vitro fertilization procedure.

CONTEXT: There is experimental but limited clinical evidence that FSH may have direct effects on bone. OBJECTIVE: The aim of the study was to evaluate the effects of acute FSH stimulation on bone turnover in premenopausal women. DESIGN AND SETTING: We conducted a prospective study at a referral center. PATIENTS: Twenty-nine infertile women (age range, 30-40 yr) undergoing an in vitro fertilization procedure were included in the study. INTERVENTIONS: Pharmacological suppression of endogenous gonadotropin and estradiol (E2) production by GnRH analog (leuprolide 1 mg/d s.c.) was followed by stimulation with recombinant FSH (rFSH; starting dose, 375 IU/d s.c.). MAIN OUTCOME MEASURES: We measured serum osteocalcin, C-telopeptides of type-1 collagen (ß-CTX), FSH, and E2 at the beginning of leuprolide administration (T0), at the beginning of rFSH administration (T1), and 3 d (T2) and 10 d (T3) after the first dose of rFSH. RESULTS: At T1, the suppression of FSH and E2 secretion, as an effect of leuprolide administration, led to a significant increase in serum ß-CTX values vs. T0 (P < 0.001). After the administration of rFSH, a rapid increase in serum FSH was observed, whereas serum E2 values increased more slowly. At T2, the increase in serum FSH values above our reference range for early follicular phase (with E2 in the reference range) did not induce any significant change in median serum ß-CTX values as compared to T1. At T3 (when both FSH and E2 were high), serum ß-CTX values decreased significantly vs. T1 (P < 0.001). Osteocalcin did not change significantly throughout the study period. CONCLUSIONS: Our model suggests that FSH does not acutely exert relevant direct effects on bone metabolism in premenopausal women.

The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomized breast cancer chemoprevention trial.

BACKGROUND: We have previously reported the favourable effect of transdermal estradiol (E2), relative to oral conjugated equine oestrogen (CEE), on ultrasensitive C-reactive protein after 12 months of treatment in a retinoid-placebo controlled two-by-two randomized breast cancer prevention trial (Decensi A et al (2002) Circulation106 10 1224-8). Here, we investigate the changes in lipids and clotting profile in patients of the same trial. METHODS AND RESULTS: Recent post-menopausal women were randomised to either oral CEE 0.625 mg/day and placebo (n = 55), CEE and fenretinide 200 mg/day (n = 56), transdermal E2 50 mg/day and placebo (n = 59) or E2 and fenretinide 200 mg/day (n = 56). Sequential medroxyprogesterone acetate 10 mg/day was given in each group. After 12 months, there was a statistically significant effect of the route of administration of hormone replacement therapy (HRT) on fibrinogen levels; the median percentage change being -5.7% with CEE and -1.1% with E2 (p = 0.012). Total cholesterol decreased in all arms (p < 0.0001). HDL-C decreased significantly with transdermal E2 (p = 0.006) compared to oral CEE and with fenretinide relative to placebo (p<0.001). Triglycerides exhibited an opposite modulation in the HRT route, with a 21.4% median increase with oral CEE and an 8.6% reduction with transdermal E2 (p < 0.0001). Antithrombin-III showed a 4% borderline significant reduction in the fenretinide arm relative to placebo, irrespective of the HRT administration route (p = 0.055). CONCLUSIONS: Our data indicate that transdermal E2 may be preferable to oral CEE based on its safer cardiovascular risk profile. Fenretinide modified some cardiovascular risk biomarkers and confirmed a safer profile compared to other retinoids.

Chromosome abnormalities and Yq microdeletions in infertile italian couples referred for assisted reproductive technique.

This study analyses the prevalence of karyotype aberrations and Yq microdeletions in infertile couples undergoing intracytoplasmic sperm injection (ICSI). Before undergoing ICSI, each partner of 470 infertile couples was screened for karyotype aberrations by QFQ-banding technique on peripheral blood lymphocytes; male partners were also screened for Yq microdeletions. In 2.55% of the couples karyotype aberrations were found including numerical and structural alterations of autosomes and sex chromosomes. The female group had a high prevalence of low-level sex chromosome mosaicism (1.28%) and 5 cases of structural autosomal abnormalities (1.06%). The male group had 7 structural abnormalities of the autosomes (1.49%), 2 supernumerary marker chromosomes (0.42%), one case of low level gonosomal mosaicism (0.21%), and 2 cases of Y chromosome inversion (0.42%). Eight cases of Yq microdeletions (1.70%) were also found. Screening for genetic factors, chromosomal abnormalities and Yq microdeletions is indicated for couples undergoing assisted reproductive techniques due to the higher prevalence of these factors in infertile couples compared to the population as a whole although different chromosome aberrations have been reported elsewhere.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Endometrial thickness and histological abnormalities in women on hormonal replacement therapy: a transvaginal ultrasound/hysteroscopic study.

OBJECTIVES: The aim of this study was to assess if endometrial thickness could be used to select postmenopausal women on hormonal replacement therapy (HRT) at increased risk for endometrial abnormalities. The secondary aim was to assess if endometrial abnormalities were more likely to occur in patients with increased endometrial thickness or in patients with unexpected bleeding. METHODS: Bi-endometrial thickness was measured by transvaginal ultrasound (TVS) in postmenopausal patients on sequential or combined HRT regimens. Women following a sequential regimen underwent TVS examination immediately after their withdrawal bleed, always between 5 and 10 days after the last progesterone tablet. A hysteroscopy with endometrial biopsy was performed within 5 days after the TVS examination, when endometrial thickness was > or = 4 mm, or when unscheduled bleeding was observed. RESULTS: A total of 190 women were recruited. In 138 women on sequential regimens, the mean value of endometrial thickness was 3.6 mm +/- 1.5, and in 52 women on combined regimens it was 3.2 mm +/- 1.8 (P = n.s.) Twenty-eight patients (15%) had an endometrial thickness > 4 mm, 35 patients (18.4%) reported unexpected bleeding. The percentage of abnormal endometrial findings (9%; three of 35) in patients selected for unscheduled bleeding was significantly lower than the percentage of abnormal findings in patients selected for hysteroscopy for endometrial thickness > 4 mm (36%; 10 of 28) (P < 0.01). All patients with unexpected bleeding and endometrial thickness < or = 4 mm (24 cases) were found to have an atrophic endometrium. CONCLUSIONS: Endometrial thickness in patients on sequential HRT, measured soon after withdrawal bleeding, is not significantly different from thickness measured in patients on combined HRT. Patients on HRT with an endometrial thickness of > 4 mm could be considered for histological sampling. The prevalence of abnormal endometrial findings in patients with a thick endometrium is significantly higher than the prevalence observed in patients with unexpected bleeding.

Ovulation induction with intravenous gonadotropin-releasing hormone.

The efficacy of ovulation induction with the use of pulsatile gonadotropin-releasing hormone (GnRH) therapy was examined in 21 infertile women. Seventeen had hypothalamic amenorrhea (HA) and 4 polycystic ovary syndrome (PCO). All patients were treated as outpatients. GnRH was infused in a pulsatile mode by means of portable auto-infusion pumps connected to an indwelling intravenous catheter inserted into a forearm vein. The doses varied from 1.8 to 5 micrograms/pulse with a frequency of 90 minutes. Ovulation occurred in 52 out of 64 cycles (81.2%). Ten (47.6%) of the 21 patients became pregnant. Seven patients had normal term deliveries and 3 aborted spontaneously. With regard to the 17 patients with HA, ovulation occurred in 93.7% of treatment cycles and 6 women became pregnant. In the case of the PCO patients, ovulation was achieved in 6 out of 15 cycles (40%) and 2 women became pregnant. There was no overstimulation or any other serious complication. In conclusion, therapy with GnRH provides an elevated probability of therapeutic success, especially in HA.

Polycystic ovary syndrome: long-term evolution.

A study was made of the long-term evolution of 64 women with PCO in order to identify the clinical and/or endocrine alterations that may modify the prognosis of each case. The patients were divided into two groups: Group A, where at the conclusion of the observation period disorders were present, and Group B, where they were not. A comparison between the clinical and endocrine data obtained from the two groups at the first observation showed only one significant difference, concerning the time of onset of menstrual irregularities; these coincided with the menarche in only 57.6% of the cases in Group A, but in 94.7% of those in Group B.

Ovarian hyperstimulation syndrome (OHS): a case of severe OHS.

A 26 year old patient, who underwent an ovulation stimulation therapy (Clomiphene /UH-FSH), monitored only by ultrasound presented a severe Ovarian Hyperstimulation Syndrome (OHS). beta-HCG values confirmed conception, that outcame in an abortion. During an ovulation stimulation therapy, patient's management with the ultrasound examination, is often inadequate and it's moreover necessary to determine the 17 beta E2 levels.

A new method for free testosterone assay: clinical evaluation.

The Authors propose a new direct method for the determination of free Testosterone (F.Te). Our study was made following this method: 1) on a control group composed of 12 healthy men and 21 healthy women, and 2) on a group of 29 patients suffering from Polycystic Ovary Syndrome (PCOS) with clinical signs of hyperandrogenism. This pathological group presented acne and hirsutism in 95% of the cases. The Authors demonstrate how the determination of F.Te permits a 93.1% correct endocrinological diagnosis of hyperandrogenism.

Treatment of hypothalamic infertility with pulsatile GN-RH administration.

In this study the Authors have obtained an ovulatory response using intravenous Gn-RH treatment in four patients with hypothalamic hypogonadotropic amenorrhea. The Gn-RH was administered in a pulsatile manner with a small portable autoinfusion pump (Autosyringe, Inc., Hooksett). The ovarian follicular maturation, as it appears from the pelvic echography, was perfectly similar to that observed in a spontaneous ovulatory cycle. Endocrine picture by serial determination of gonadotropin; prolactin, estradiol and progesterone concentrations showed hormone values to be in the normal range. During the therapy no complications were observed; at the present time no pregnancy has occurred.

Profiles and endocrine correlations in endometrial carcinoma.

The Authors compared the mean LH, FSH, PRL, E1, E2, Testosterone, Androstenedione plasmatic levels in a group of post-menopausal women affected by endometrial carcinoma (EK), with those of a control group presenting clinical characteristics as close as possible to those of the pathologic group. The case series was significant. They found no significant difference between the two groups' hormonal levels. On the other hand, E1 levels were found to increase along-side with obesity. In patients affected by EK, E1 plasma levels significantly increased alongside with the post-menopausal age. Conversely, in the control group, this hormonal value significantly and progressively decreased from the menopause onwards. Furthermore, the Authors studied the effects of surgical intervention on the hormonal picture in EK bearers.