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.

CONTEXTThere is experimental but limited clinical evidence that FSH may have direct effects on bone.OBJECTIVEThe aim of the study was to evaluate the effects of acute FSH stimulation on bone turnover in premenopausal women.DESIGN AND SETTINGWe conducted a prospective study at a referral center.PATIENTSTwenty-nine infertile women (age range, 30-40 yr) undergoing an in vitro fertilization procedure were included in the study.INTERVENTIONSPharmacological 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 MEASURESWe measured serum osteocalcin, C-telopeptides of type-1 collagen (β-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.RESULTSAt T1, the suppression of FSH and E2 secretion, as an effect of leuprolide administration, led to a significant increase in serum β-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 β-CTX values as compared to T1. At T3 (when both FSH and E2 were high), serum β-CTX values decreased significantly vs. T1 (P < 0.001). Osteocalcin did not change significantly throughout the study period.CONCLUSIONSOur model suggests that FSH does not acutely exert relevant direct effects on bone metabolism in premenopausal women.

OBJECTIVE: To evaluate the efficacy of acupuncture on pregnancy rate in patients undergoing IVF. DESIGN: Prospective randomised controlled trial. MATERIALS AND METHODS: 168 patients undergoing embryo transfer, consecutively enrolled in our IVF clinic, were randomised between between acupuncture and observation in the period may-december 2009. The informed patients who accepted and were randomly assigned to acupuncture group have been treated with needles inserted 25 minutes before and after embryo transfer. The selection of points was performed, in an effort to positively influence blood flow and energy to the uterus and to provide sedative effect, according to different sequences: before transfer Yintang, Hegu, Zusanli, Sanyinjiao, Taichong, after transfer along points Shenmen, uterus, kidney and heart. RESULTS: The patients were evenly distributed according to age (35.8 ± 4.3 vs 35.6 ± 3.8), transferred embryos (2.1 ± 1.4 vs 2.0 ± 2.1), and IVF clinical indication. No losses at follow up were observed. No adverse effects of acupuncture were reported. The pregnancy rate per transfer (as documented by positive beta-HCG) was 50% in the acupuncture group vs 34.6% in the no-treatment arm. The clinical pregnancy rate, as documented by positive US scan 6 weeks after IVF procedure, was 45% and 28% respectively. CONCLUSION: Acupuncture performed on the day of embryo transfer appears to increase pregnancy rates in women undergoing in vistro fertilization.

OBJECTIVE: Two single nucleotide polymorphisms at position 680 and 307 of the FSH receptor gene have been associated with infertility and ovarian response in IVF. The aim of this study was to examine the frequency distribution of FSH receptor polymorphisms in infertile patients and controls and to correlate these polymorphisms with the outcome of IVF cycle. DESIGN: Case-control study. MATERIALS AND METHODS: 86 IVF infertile patients undergoing ovarian stimulation in a long suppression protocol and 60 fertile controls were included in the study. Fertile patients included were enrolled among women who delivered and had no history of infertility. Blood samples were obtained and DNA was analyzed to determine the FSH receptor genotype. Among IVF cycle: basal FSH levels, number of antral follicles, number of preovulatory follicles (>15mm), number of retrieved oocytes, duration of stimulation (days), number of transfer embryo, pregnancy rate and amount of FSH were assessed and correlated with genotypes. RESULTS: No statistically significant differences in the distribution of polymorphisms were found among the group of infertile women and controls. Basal FSH levels, number of antral follicles, number of preovulatory follicles (>15mm), number of retrieved oocytes and number of transfered embryos was comparable between infertile patients with different FSH receptor genotype. However, patients who carry TT (thr-thr) and NN (asn-asn) genotype need fewer days of ovarian stimulation to oocyte retrieval. (TT: 9,07 days, p=0,028; NN: 9,08 days, p=0,037). A trend of better pregnancy rate in the AA genotype carrying patients was found, although not statistically significant. The dose of FSH required for a successful stimulation was similar in the two polymorphisms. CONCLUSIONS: FSH receptor genotype is not different between infertile and fertile patients. TT and NN genotype acchieve a significantly higher ovarian response. There is a not significant trend for better pregnancy rate in AA subgroup patients. Our results seem to support some role of FSH receptor polymorphism in infertile patients: the clinical relevance of this factor is however probably low.

OBJECTIVE: The aim of this study was to prospectively evaluate the predictive value of serum progesterone levels as measured on the day of oocyte retrieval on pregnancy rate and stimulation response. DESIGN: Retrospective study. MATERIALS AND METHODS: We prospectively evaluated 79 consecutive patients treated by FIVET/ICSI. Serum progesterone was measured the day of oocyte retrieval. The mean age of patients was 38,1 and mean BMI was 22,3. All patients underwent gonadotropins ovarian stimulation and pituitary suppression with either GnRh agonist or antagonist. Pregnancy was defined as beta HCG levels greater than 5 UI two weeks after the oocyte retrieval and vital embryo visible on trans vaginal ultrasound at 6 weeks gestation. The date were than analyzed with respect to serum progesterone levels on the day of oocyte retrieval with the chi-squared test. RESULTS: Among 79 patients, 12 had a viable intrauterine pregnancy at 6 weeks of gestation. Age, BMI and FSH on third day of cycle between pregnant and not pregnant patients were statistically similar. In cycles with high serum progesterone levels, there were more follicle > 15 mm (p=0,0001); more oocyte were retrieved (p=0,0001) and more embryos were available for transfer (p=0,046). There were no significant differences in the progesterone levels on the day of oocyte retrieval in pregnant or not pregnant patients. CONCLUSIONS: Serum progesterone levels on the day of oocyte retrieval appear not to be correlated significantly with pregnancy rate. However high progesterone levels were significantly correlated with higher number of follicles >15mm, with oocytes retrieved and embryos transferred.

OBJECTIVE: To evaluate the role of sonohysterography in the diagnosis of intrauterine pathology in comparison to hysteroscopy. DESIGN: Prospective study using sonohysterography as a first step examination of uterine cavity in a group of infertile women during 18 months. MATERIALS AND METHODS: 444 sonohysterography were performed from January 2005 to april 2007. The mean age of patients was 35 (range 23-42). In 23 patients the exam was not possible due to cervical stenosis (5,2%). The sonohysterography was performed between 10-15 day of the menstrual cycle. If a diagnosis of possible intrauterine anomaly was made at sonohysterography, hysteroscopy was scheduled. Comparative results of sonohysterography and hysteroscopy has been analyzed. Positive predictive value (PPV) and specificity of sonohysterography have been calculated. RESULTS: In 58 of 421 patients (15,4%), sonohysterography showed an abnormal uterine cavity: 36 polyps (8,5%), 3 submucous myomas (0,7%), 18 uterine malformation (4,3%), 1 synechiae (0,2%), 7 non accessible cavity (1,7%). Among these patients, 51 underwent diagnostic hysteroscopy. Hysteroscopy revealed 34 polyps, 2 myomas, 1 synechiae, 9 uterine malformation and 3 normal cavity. PPV of sonohysterography was 94% for polyps detection, 100% for myomas, 100% for synechiae, 90% for uterine malformation. Overall PPV has been 94%. CONCLUSIONS: Sonohysterography is a simple, low cost and well tolerated procedure. Diagnostic accuracy and the low false positive rate suggest sonohysterography as a routine test in the evaluation of the uterine cavity of infertile women.

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.

genes 207, 286 Chicken sex determination 279 Chromosome(s) 161 -aberrations 347 Coelomic epithelium 238, 271 Comparative genomics 211 Cystatin type 2 family

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.

Objective: We analysed risk factors for high blood pressure (BP) among women around menopause.Methods: Eligible women were consecutively attending first-level outpatient menopause clinics in Italy for general counseling or treatment of menopausal symptoms. During the visit BP was measured three times. The mean of second and third of the three diastolic BP values for women was > 90 mm of mercury and/or reporting any current pharmacological treatment for high BP were considered hypertensive. Out of 45,204 women who entered the study with information on blood pressure, 12,150 had high BP.Results: The odds ratios (OR) of high BP increased with age: in comparison with women aged < 50 years, the multivariate OR were 1.44 (95% confidence interval (CI), 1.34-1.55), 1.61 (95% CI, 1.50-1.74) and 1.91 (95% CI, 1.77-2.06) in women aged 51-53, 54-57 and >= 58, respectively. Women with high BP were less educated than those without (OR education > 12 versus < 7 years, 0.79, 95% CI, 0.74-0.84). In comparison with women with a body mass index (BMI) < 24, the multivariate ORs were 1.48 (95% CI, 1.39-1.57) and 2.56 (95% CI, 2.41-2.71) for women with BMI 24-26 and > 26. In comparison with women reporting no regular physical activity, the multivariate OR of high BP was 0.93 (95% CI, 0.87-0.99) for women reporting regular activity. In comparison with peri-menopausal women, post-menopausal women were at increased risk (OR 1.14, 95% CI, 1.03-1.24) and the risk tended to increase with age at menopause. Current use of hormonal replacement therapy (HRT) was associated with a lower risk of high BP (OR 0.88, 95% CI, 0.84-0.94).Conclusions: This large cross-sectional study suggests that, after taking into account the effect of age, post-menopausal women are at greater risk of high BP, but current HRT use slightly lowers the risk. Other determinants of high BP were low level of education, overweight, and low level of physical activity. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

ObjectiveA 2004 Italian regulation, indicates that during assisted reproductive technologies (ART) all fresh fertilized embryos should be transferred. The same regulation states that transferred embryos should not exceed the number of three and that embryos freezing is not permitted. Due to this reason it is allowed to fertilize not more than three oocytes per patient and per cycle. In this study, we investigated the impact of this law regulation on the ART results, comparing two consecutive series of patients, recruited before and after its onset.DesignRetrospective clinical studyMaterials and methodsA total of 108 and 114 different patients undergoing ART between June and December 2003 and between June and December 2004 were included. Inclusion criteria: woman’s age ≤ 41 years, integrity of both ovaries, informed consent. Three different patient categories (poor, normal and high responder) have been identified using clinical, biochemical and sonographic parameters. “Poor” responder patients were 17 in 2003 and 24 in 2004, “normal” were 66 in 2003 and 68 in 2004, “high” were 25 in 2003 and 22 in 2004; all patients were therefore included in 3 different ovulation induction regimens. The ovarian stimulation has been monitored by transvaginal sonography and estradiol measurements until ovulation induction. A total of 56 (51.9%) patients underwent ICSI in 2003 and 52 (45.6%) in 2004; 52 (48.9%) in 2003 and 62(54.4%) in 2004 underwent FIVET procedure. The selection of the treatment was performed using FSH, LH and estradiol level, sonographically visible antral follicle count, ovarian volume size, body mass index (BMI) and age of patients. The number of retrieved and inseminated oocytes, cleavaged and transferred embryos, cancelled cycles, the incidence of multiple gestations and miscarriages have been evaluated. The results have been expressed as mean and standard deviation; the X2 test was used in the comparison of the groups. A P value < .05 was considered statistically significant.ResultsA significantly lower number of inseminated oocytes and cleavaged embryos has been observed in the group of normal and high responders in 2004 versus 2003. In poor responders group and in the total number of patients a significantly lower number of retrieved, inseminated oocytes, cleavaged and transferred embryos in 2004 versus 2003. No-oocyte recovery occurrence, failure of fertilization, twin pregnancies and miscarriages were similar in all groups. The pregnancy rate (PR) per transfer in the “normal” responders was 37% in 2004 vs 46,2% in 2003, in the “high” responders was 29.4% in 2004 vs 45.0% in 2003, in the “poor” responders was 37.5% in 2004 vs 18.2% in 2003, and finally among the whole series was 35.4% in 2004 vs 42.2% in 2003. The 2003 vs 2004 data analysis showed significant differences between standard FIVET and ICSI: FIVET patients had a lower number of inseminated oocytes and cleavaged embryos, ICSI patients and the whole series had a lower number of retrieved and inseminated oocytes, cleavaged and transferred embryos. Cancelled cycles, multiple pregnancy and miscarriages incidence were not different in the three groups. The PR per transfer in the standard FIVET group was 43.7% in 2004 vs 52.4% in 2003, in the ICSI group was 22.5% in 2004 vs 31.7% in 2003.ConclusionOur results show that this present new Italian regulation caused a detrimental effect on the pregnancy rates for all the patients undergoing ART. ObjectiveA 2004 Italian regulation, indicates that during assisted reproductive technologies (ART) all fresh fertilized embryos should be transferred. The same regulation states that transferred embryos should not exceed the number of three and that embryos freezing is not permitted. Due to this reason it is allowed to fertilize not more than three oocytes per patient and per cycle. In this study, we investigated the impact of this law regulation on the ART results, comparing two consecutive series of patients, recruited before and after its onset. A 2004 Italian regulation, indicates that during assisted reproductive technologies (ART) all fresh fertilized embryos should be transferred. The same regulation states that transferred embryos should not exceed the number of three and that embryos freezing is not permitted. Due to this reason it is allowed to fertilize not more than three oocytes per patient and per cycle. In this study, we investigated the impact of this law regulation on the ART results, comparing two consecutive series of patients, recruited before and after its onset. DesignRetrospective clinical study Retrospective clinical study Materials and methodsA total of 108 and 114 different patients undergoing ART between June and December 2003 and between June and December 2004 were included. Inclusion criteria: woman’s age ≤ 41 years, integrity of both ovaries, informed consent. Three different patient categories (poor, normal and high responder) have been identified using clinical, biochemical and sonographic parameters. “Poor” responder patients were 17 in 2003 and 24 in 2004, “normal” were 66 in 2003 and 68 in 2004, “high” were 25 in 2003 and 22 in 2004; all patients were therefore included in 3 different ovulation induction regimens. The ovarian stimulation has been monitored by transvaginal sonography and estradiol measurements until ovulation induction. A total of 56 (51.9%) patients underwent ICSI in 2003 and 52 (45.6%) in 2004; 52 (48.9%) in 2003 and 62(54.4%) in 2004 underwent FIVET procedure. The selection of the treatment was performed using FSH, LH and estradiol level, sonographically visible antral follicle count, ovarian volume size, body mass index (BMI) and age of patients. The number of retrieved and inseminated oocytes, cleavaged and transferred embryos, cancelled cycles, the incidence of multiple gestations and miscarriages have been evaluated. The results have been expressed as mean and standard deviation; the X2 test was used in the comparison of the groups. A P value < .05 was considered statistically significant. A total of 108 and 114 different patients undergoing ART between June and December 2003 and between June and December 2004 were included. Inclusion criteria: woman’s age ≤ 41 years, integrity of both ovaries, informed consent. Three different patient categories (poor, normal and high responder) have been identified using clinical, biochemical and sonographic parameters. “Poor” responder patients were 17 in 2003 and 24 in 2004, “normal” were 66 in 2003 and 68 in 2004, “high” were 25 in 2003 and 22 in 2004; all patients were therefore included in 3 different ovulation induction regimens. The ovarian stimulation has been monitored by transvaginal sonography and estradiol measurements until ovulation induction. A total of 56 (51.9%) patients underwent ICSI in 2003 and 52 (45.6%) in 2004; 52 (48.9%) in 2003 and 62(54.4%) in 2004 underwent FIVET procedure. The selection of the treatment was performed using FSH, LH and estradiol level, sonographically visible antral follicle count, ovarian volume size, body mass index (BMI) and age of patients. The number of retrieved and inseminated oocytes, cleavaged and transferred embryos, cancelled cycles, the incidence of multiple gestations and miscarriages have been evaluated. The results have been expressed as mean and standard deviation; the X2 test was used in the comparison of the groups. A P value < .05 was considered statistically significant. ResultsA significantly lower number of inseminated oocytes and cleavaged embryos has been observed in the group of normal and high responders in 2004 versus 2003. In poor responders group and in the total number of patients a significantly lower number of retrieved, inseminated oocytes, cleavaged and transferred embryos in 2004 versus 2003. No-oocyte recovery occurrence, failure of fertilization, twin pregnancies and miscarriages were similar in all groups. The pregnancy rate (PR) per transfer in the “normal” responders was 37% in 2004 vs 46,2% in 2003, in the “high” responders was 29.4% in 2004 vs 45.0% in 2003, in the “poor” responders was 37.5% in 2004 vs 18.2% in 2003, and finally among the whole series was 35.4% in 2004 vs 42.2% in 2003. The 2003 vs 2004 data analysis showed significant differences between standard FIVET and ICSI: FIVET patients had a lower number of inseminated oocytes and cleavaged embryos, ICSI patients and the whole series had a lower number of retrieved and inseminated oocytes, cleavaged and transferred embryos. Cancelled cycles, multiple pregnancy and miscarriages incidence were not different in the three groups. The PR per transfer in the standard FIVET group was 43.7% in 2004 vs 52.4% in 2003, in the ICSI group was 22.5% in 2004 vs 31.7% in 2003. A significantly lower number of inseminated oocytes and cleavaged embryos has been observed in the group of normal and high responders in 2004 versus 2003. In poor responders group and in the total number of patients a significantly lower number of retrieved, inseminated oocytes, cleavaged and transferred embryos in 2004 versus 2003. No-oocyte recovery occurrence, failure of fertilization, twin pregnancies and miscarriages were similar in all groups. The pregnancy rate (PR) per transfer in the “normal” responders was 37% in 2004 vs 46,2% in 2003, in the “high” responders was 29.4% in 2004 vs 45.0% in 2003, in the “poor” responders was 37.5% in 2004 vs 18.2% in 2003, and finally among the whole series was 35.4% in 2004 vs 42.2% in 2003. The 2003 vs 2004 data analysis showed significant differences between standard FIVET and ICSI: FIVET patients had a lower number of inseminated oocytes and cleavaged embryos, ICSI patients and the whole series had a lower number of retrieved and inseminated oocytes, cleavaged and transferred embryos. Cancelled cycles, multiple pregnancy and miscarriages incidence were not different in the three groups. The PR per transfer in the standard FIVET group was 43.7% in 2004 vs 52.4% in 2003, in the ICSI group was 22.5% in 2004 vs 31.7% in 2003. ConclusionOur results show that this present new Italian regulation caused a detrimental effect on the pregnancy rates for all the patients undergoing ART. Our results show that this present new Italian regulation caused a detrimental effect on the pregnancy rates for all the patients undergoing ART.

Objective To obtain data on correlates of total cholesterol (TC) levels in women around menopause attending menopause clinics in Italy.Methods Since 1997, a large cross-sectional study has been conducted concerning the characteristics of women around the time of the menopause attending a network of first-level menopause out-patient clinics in Italy for general counselling about the menopause or treatment of menopausal symptoms. Women observed consecutively at the participating centers were eligible for the study. Up to March 2000, TC was measured in 23 018 cases, which are considered in this analysis.Results The adjusted mean level of TC rose with age, from 216 mg/dl in women aged < 50 years to 234 mg/dl in those aged > 57 years. Mean TC increased with body mass index (BMI, kg/m(2)), being 224 mg/dl in women with BMI < 24, 227 mg/dl in those with BMI 24-26 and 228 mg/dl in those with BMI > 26. Considering menopausal status, the crude mean TC level was 216 mg/dl in premenopausal women, 227 mg/dl in women reporting a surgical menopause and 229 mg/dl in women reporting a natural menopause. These differences were still present when the analysis took into account the effect of age and other potential covariates, the adjusted values being 221, 225 and 227, respectively. Similar findings emerged when we considered the distribution of study subjects according-to selected levels of TC (< 210, 210-250, 251-290, < 290). For example, the odds ratio of TC 210-250 mg/dl and > 250 mg/dl vs. < 210 mg/dl was, respectively, 1.8 and 2.8 in women aged greater than or equal to 57 years in comparison with women aged < 50 years. The corresponding odds ratio values for women with a BMI > 26 vs. < 24, and for women in spontaneous menopause vs. premenopause, were all 1.2 (all statistically significant).Conclusions This analysis, based on a large data set, confirms the role of overweight as a determinant of TC in postmenopausal women, and indicates the role of the menopause as a determinant of TC level in women aged 50-60 years.

Purpose: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo.Experimental Design: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 mug/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided.Results: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39).Conclusions: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.

OBJECTIVE:To assess the value of endometrial thickness as a marker of endometrial abnormality risk during hormone therapy (HT) and to study the correlation between abnormal bleeding and abnormal endometrial histology in patients with thick endometrium.DESIGN:Prospective multicenter study.SETTING:University and general hospitals outpatient centers.PATIENT(S):Postmenopausal women (702) on HT.INTERVENTION(S):Biendometrial thickness was measured by transvaginal sonography (TVS) between day 5 and day 10 after the last P intake and, when present, after the end of the menstrual-like bleeding.MAIN OUTCOME MEASURE(S):Hysteroscopy and biopsy were performed within 5 days from TVS on all patients with an endometrial thickness >4.5 mm (precision scale 0.5 mm).RESULT(S):Endometrial thickness >4.5 mm was observed in 20.5% of patients. One hundred sixteen hysteroscopies and biopsies were performed. Hyperplasia, polyps, and endocavitary fibroids were detected in 15%, 24%, and 8% of cases, respectively. The positive predictive value of TVS examination was 47%. Endometrial thickness was the only variable significantly and independently associated with histologic abnormalities and endocavitary fibroids. Abnormal bleeding occurred in 17.1% of patients. Among 17 patients detected with thick endometrium and hyperplasia, 8 cases showed abnormal bleeding.CONCLUSION(S):Sonographic endometrial thickness of 4.5 mm provides a sensitive tool to select HT patients who might benefit from hysteroscopy and biopsy. Abnormal bleeding is not a sensitive sign of hyperplasia in patients with thick endometrium.

Objective To determine the frequency and causes of preterm ovarian failure (menopause before 40 years of age) and early menopause (menopause between 40 and 45 years).