Domenico De Aloysio

The effect of dietary soy supplementation on hot flushes.

Objective To study infectious pathology at index ectopic pregnancy and to determine what other factors predispose a woman to repeat ectopic pregnancy. Methods All women (n = 697) with their first (index) ectopic pregnancy histologically verified between January 1, 1978, and December 31, 1993, at the only two hospitals in one Norwegian county were eligible. Included were permanent residents of the county who were 37 years of age or younger and who had not had tubal surgery before the index pregnancy. When the study closed on November 1, 1994, the participants had been observed prospectively for fertility events from approximately 1 to 17 years. Included in the final analyses were 353 women who had from one to five natural conceptions, for a total of 555 pregnancies. Chisquare test was used in univariate analysis, and the generalized estimating equations approach was used to analyze correlated responses and covariates that changed over time. Results Pregnancy order is the stronger correlate of subsequent ectopic pregnancy. The frequency of repeat ectopic pregnancy decreased by one-third for each pregnancy from the first to the third pregnancy. The odds of having another ectopic pregnancy were nearly three times higher for women with a diagnosis of infectious pathology than for women who had no infectious pathology. Other correlates of repeat ectopic pregnancy include age 24 years or younger at first ectopic pregnancy, history of repeat ectopic pregnancy, initiation of infertility work-up, and conception with an intra-uterine device at index pregnancy. Method of surgery was not associated with repeat ectopic pregnancy. Conclusion The most crucial reproductive event after first ectopic pregnancy is the first event to occur. Women who have experienced two ectopic pregnancies should be considered candidates for assisted reproduction.

Phalangeal Osteosonogrammetry Study: Age‐Related Changes, Diagnostic Sensitivity, and Discrimination Power

Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude‐dependent speed of sound [AD‐SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD‐SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X‐ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD‐SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD‐SOS was odds ratio (OR) 1.71 (CI, 1.58‐1.84). The AD‐SoS in fractured subjects was significantly lower than in a group of age‐matched nonfractured subjects (p < 0.0001). In a small cohort of hip‐fractured patients UBPI proved to be lower than in a control age‐matched group (p < 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD‐SoS we found a T score of −3.2 and for UBPI we found a T score of −3.14. Sixty‐six percent of vertebral fractures were below the AD‐SoS −3.2 T score and 62% were below UBPI −3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD‐SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.

Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women

ABSTRACT Our aim was to evaluate the prevalence of bacterial vaginosis and decrease in lactobacillus colonization in women 40 years old or older in relation to menopausal status by evaluation of Gram-stained smears. A total of 1,486 smears from Italian Caucasian women aged 40 to 79 years were examined. Women were classified as follows: fertile (regular cycles) (n = 328), perimenopausal (irregular cycles) (n = 237), and postmenopausal (n = 921), including 331 women on estroprogestinic hormone replacement therapy (HRT). The prevalences of bacterial vaginosis (assessed as a Nugent score of ≥7) in fertile (9.8%) and perimenopausal (11.0%) women were not statistically different, whereas the prevalence was significantly lower overall in postmenopausal women (6.0%) (P = 0.02). Specifically, 6.3% of postmenopausal women without HRT and 5.4% of postmenopausal women with HRT were positive for bacterial vaginosis. The Nugent score system was not adequate for evaluating the normal and intermediate vaginal flora in women over the age of 40 years. High numbers of peri- and postmenopausal women had no lactobacilli and no bacterial-vaginosis-associated microorganisms. This nonpathological absence of lactobacilli in women with a Nugent score of 4 was scored as 4∗, and this group was considered separately from the intermediate flora group. A score of 4∗ was obtained for 2.1% of fertile women, 11.4% of perimenopausal women, 44.1% of postmenopausal women without HRT, and 6.9% of postmenopausal women with HRT. The physiological reduction in lactobacillus colonization of the vagina in postmenopausal women does not cause an increase in bacterial-vaginosis prevalence. Reversion of lactobacillus flora to premenopausal levels due to HRT does not increase the prevalence of bacterial vaginosis in postmenopausal women.

Three-year longitudinal study with quantitative ultrasound at the hand phalanx in a female population

A longitudinal study was conducted to assess the value of quantitative ultrasound (QUS) measurement in predicting the risk of fracture and to evaluate how QUS parameters change with ageing and the climacteric. A group of 211 female subjects underwent assessment by QUS at the distal metaphysis of the first phalanx of the last four fingers of the hand on two occasions 3 years apart. The subjects were selected from outpatients attending the orthopaedic clinic, provided they were not affected by metabolic disease or under treatment with drugs known to interfere with bone metabolism. In vivo the coefficient of variation and the standardized coefficient of variation of the QUS device were respectively 0.5% and 3.5%. The correlation between the values of the amplitude-dependent speed of sound (AD-SoS) in the two measurements wasr=0.92. In 77.3% of the subjects during the observation period we recorded a reduction in AD-SoS. During the study 22 fractures were observed in peripheral sites, 8 of which were associated with ‘low-energy trauma’. By multiple logistic regression analysis we found that the relative risk of fracture for a 1 SD reduction in AD-SoS was 1.5 (95% CI 1.1–1.7) (p<0.03). The percentage of low-energy fractures significantly increased among those subjects with an AD-SoS value lower than 1850 m/s (T-score <−3.5) at the first examination (p<0.0001). QUS investigation proved to be especially sensitive to hormonal changes associated with the climacteric: we observed a mean decrease of 56 m/s in the AD-SoS for women who entered the menopause between the first and the second QUS test (average time since menopause 2 years), as against 10 m/s in subjects remaining premenopausal. In a group of 146 subjects with ‘normal’ AD-SoS at the first examination, we observed a significant reduction in AD-SoS only after 40 years of age. This study demonstrates that measurement of the AD-SoS at the phalanx is reproducible, can be employed to assess the risk of fracture, and is able to detect age-related alterations in bone tissue.

The effect of menopause on blood lipid and lipoprotein levels

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Determinants of age at menopause in Italy: results from a large cross-sectional study

OBJECTIVE To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS ICARUS is a prospective study of the effect of menopause on womens health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

Risk factors for genital prolapse in non-hysterectomized women around menopause: Results from a large cross-sectional study in menopausal clinics in Italy

OBJECTIVE To analyze determinants/risk factors for uterine prolapse in a population of women around menopause. METHODS Between 1997 and 1999, we conducted a large cross sectional study on the characteristics of women around menopause attending a network of first level outpatients menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. Eligible for the study were women consecutively observed during the study period. All women underwent a gynecological examination. RESULTS Considering the 21,449 non-hysterectomized women, uterine prolapse was diagnosed in 1182 cases (5.5%). Of those, 772 (65.3%) had prolapse degree I and 410 (34.7%) degree II or III. The frequency of uterine prolapse increases with age: In comparison with women aged < or = 51 years, the odds ratio OR of uterine prolapse was 1.3 and 1.7 respectively for women aged 52-55 and > or = 56 years. In comparison with women with none/primary education, the OR of uterine prolapse was 0.8 (95% confidential interval CI 0.7-0.9) and 0.8 (95% CI 0.6-0.9), respectively, for women with intermediate or high school/university degree. The risk of uterine prolapse increased with body mass index (BMI; kg/m(2)) value: In comparison with women with BMI<23.8, the OR was 1.4 (95% CI 1.2-1.7) and 1.6 (95% CI 1.3-1.9) for women with BMI 23.8-27.2 and >27.2. In comparison with nulliparae, the OR of uterine prolapse increased with number of births, being 3.0 (95% CI 2.1-4.3) in women reporting > or = 3 births. A history of caesarean section or of a delivery of a fetus weighing >4500 g were not associated with increased risk of uterine prolapse. When the analysis was conducted separately in strata of grade of uterine prolapse (I and > or = II), no marked differences emerged in the OR estimates. CONCLUSIONS This study indicates that, in this population, the risk of uterovaginal prolapse increase with the number of vaginal births and was higher in overweight women, offering some quantitative estimates of the role of these factors on the risk of the condition.

Dietary soy supplementation and phytoestrogen levels

OBJECTIVE To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. METHODS Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. RESULTS Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. CONCLUSION Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.

Vascular Risk in Young Women With Polycystic Ovary and Polycystic Ovary Syndrome

OBJECTIVE: To estimate if young polycystic ovary syndrome (PCOS) patients have subclinical risks of vascular disease compared with eumenorrheic polycystic ovary (PCO) women and healthy controls. METHODS: Twenty-eight PCOS patients, 17 eumenorrheic PCO women, and 15 healthy eumenorrheic volunteers underwent medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; uteroovarian ultrasonographic analysis and color Doppler evaluation of uterine, stromal ovarian, and ophthalmic arteries; brachial artery flow–mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide. RESULTS: Doppler analysis revealed a significantly higher uterine pulsatility index in the PCOS group compared with controls. The lowest vascular resistances in the ovaries were found in PCOS and PCO compared with controls. The ophthalmic artery back pressure was significantly higher in women with PCOS than in controls. The brachial artery diameter, at baseline, was similar in all the participants. After the reactive hyperemia, a greater vasodilatation was observed in controls and PCO patients in comparison with PCOS women. Total cholesterol, triglycerides, and the atherogenic plasma index were significantly higher in PCOS than PCO and controls. Leukocytes and homocysteine were slightly higher in PCOS. The nitrites/nitrates plasma levels were lower in PCOS and PCO patients compared with controls. The insulin and C-peptide plasma values were higher in PCOS patients than controls. In PCOS patients the different estimates of insulin sensitivity and pancreatic β-cell function were higher compared with PCO and controls. CONCLUSION: Polycystic ovary syndrome is a condition associated with an increased vascular risk. LEVEL OF EVIDENCE: II

Menstrual Cycle‐Related Morphometric and Vascular Modifications of the Clitoris

INTRODUCTION The evaluation of clitoral anatomy and function is of paramount importance to understand the physiology and pathology of clitoral function. AIM To prospectively evaluate the clitoral volumetric and vascular modifications during the menstrual cycle, and analyze their relationship with circulating hormones and nitric oxide levels. METHODS Thirty healthy eumenorrheic women were studied in different phases of the menstrual cycle (day 3, 10, 14, 20, and 27). They were submitted to ultrasonographic (US) and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES Transvaginal US evaluation of uterus, ovaries, and clitoris; Doppler analysis of uterine and dorsal clitoral arteries; and measurement of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, androstenedione, testosterone, and nitrites/nitrates concentration. Sex hormone binding globulin was assayed, and free androgen index was calculated. RESULTS During the menstrual cycle, FSH, LH, and estradiol changed as expected, whereas androgens did not show any significant change. The US assessment of the clitoral body volume evidenced a progressive increase with significant modifications during the periovulatory phase, after which it remained stable until day 20. Subsequently, the clitoral body volume decreased into the premenstrual phase (day 27), reaching values similar to those observed on cycle day 3. A comparable trend was observed in the nitrite/nitrate circulating values. The uterine and clitoral arteries presented significant modifications with reduced resistances in the periovulatory period. Estradiol levels resulted positively correlated with the clitoral body volume and inversely correlated with the dorsal clitoral artery pulsatility index (PI). Furthermore, the dorsal clitoral artery PI was inversely and significantly correlated with the nitrite/nitrate circulating values and the clitoral body volume. CONCLUSIONS Clitoral anatomic and vascular modifications are observable during the normal menstrual cycle.