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Biomedical subjects

G Secreto

Publications and source records attributed to G Secreto.

At least 19 recordsLinked to original sources
PubMed2003

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aged↗
PubMed2003

Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial.

OBJECTIVE: To assess the effects of a comprehensive change in dietary composition on endogenous hormone metabolism. The specific aim was to examine whether this intervention could lead to favourable changes in insulin sensitivity, levels of IGF-I and IGF-binding proteins (IGFBPs), and total and bioavailable testosterone and estradiol, that would be expected to reduce breast cancer risk. DESIGN: Randomised dietary intervention study; duration of 5 months. SUBJECTS: From a total of 99 postmenopausal women, who had elevated baseline plasma testosterone levels, 49 women were randomly assigned to the dietary intervention arm and the other 50 to a control group. INTERVENTIONS: Main aspects of the dietary intervention were reductions in the intake of total fat and refined carbohydrates, an increase in the ratio of n-3 over n-6 plus saturated fatty acids, and increased intakes of foods rich in dietary fibre and phytooestrogens. RESULTS: Relative to the control group, women of the intervention group showed a significant reduction of body weight, waist circumference, fasting serum levels of testosterone, C peptide, glucose, and insulin area after glucose tolerance test, and a significant increase of serum levels of sex hormone-binding globulin, IGFBP-1, -2, and growth hormone-binding protein. Serum levels of IGF-I did not change. CONCLUSION: This comprehensive dietary intervention strategy proved to be successful in inducing changes in endogenous hormone metabolism that might eventually result in reduced breast cancer risk. Additional studies are needed to show whether the dietary intervention and related hormonal changes can be both maintained over longer periods, of at least several years.

Aged↗
PubMed2002

Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial.

OBJECTIVES: To compare the effect of a soy rich diet and hormone replacement therapy (HRT) on the main biomarkers of bone turnover and bone mineral density (BMD) at postmenopausal age. METHODS: 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into a soy rich diet group, a HRT group, and a control group. Bone biomarkers and BMD were evaluated at baseline and after 6 months at the end of the study. RESULTS: Diet is not as effective as HRT in reducing the postmenopausal turnover; however diet stimulates bone osteoblastic activity, as evidenced by significant increase in osteocalcin concentrations. BMD decreases significantly only in the control group, but not in the intervention groups. CONCLUSIONS: Our data suggest that soy products could be effective in reducing the risk of osteoporosis in asymptomatic postmenopausal women, but our findings should be confirmed before recommending the diet as a valid alternative to HRT.

Adult↗
PubMed2002

The effects of a soy rich diet on serum lipids: the Menfis randomized trial.

OBJECTIVE: To assess beneficial effects of a soy rich diet on the main biomarkers of cardiovascular health in menopause, compared with the effects of the hormone replacement therapy (HRT). METHODS: 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into three groups: a soy rich diet group, a HRT group, and a control group. Lipid profile, body mass index, blood pressure, endometrial thickness, uterine artery resistance index (RI), were evaluated in all the participants at the baseline, after 6 months, and at the end of the study. RESULTS: After a 6-month intervention period, the lipid profile in the soy rich diet group showed a favourable outcome, similar to that observed in the HRT group, but compliance to the diet was low. CONCLUSION: Soy products may be used in the prevention of cardiovascular risk in postmenopausal women because of their efficacy in contrasting the negative effects of menopause on the cardiovascular system, but our findings should be confirmed; moreover, suitable strategies to improve the compliance have to be considered.

Adult↗
PubMed2001

Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.

High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.

Aged↗
PubMed2001

Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women.

In large-scale epidemiological studies on endogenous sex steroids and cancer risk, direct immunoassays of circulating hormone levels have the advantage of being fast and comparatively inexpensive while requiring only small sample volumes. On the other hand, indirect assays after organic extraction and chromatographic prepurification have the advantage of reducing specific interferences and matrix effects and hence are thought to have better validity. We compared direct assays of testosterone (T, six different assays), Delta4-androstenedione (A, four assays), estrone (E(1), one assay), and 17beta-estradiol (E(2), five assays) with measurements obtained by an indirect assay in a representative subset of 20 postmenopausal women who were part of a large prospective cohort study. Within-batch reproducibilities of the subject rankings by relative hormone levels were good (intraclass correlations >0.89) for all direct assays tested. Between batches, reproducibilities generally were also acceptable (r > 0.80) to good (r > 0.90) in terms of Pearson's correlations. The between-batch reproducibility in terms of intraclass correlations was systematically lower in terms of Pearson's correlations, however, because of between-batch variations in the absolute scale of measurements. The relative validity of direct versus indirect assays in terms of the subjects' ranking by relative hormone levels was also high for most of the kits tested for T, A, and E(1) (Pearson's correlations between 0.70 and 0.89) but was high for only two kits of five tested for E(2) (correlations of 0.86 and 0.84). On an absolute scale, mean measurement values were generally higher for direct assays than for the indirect assay and, for each hormone, varied substantially, depending on the kit used. Overall, the results of this study show that, with careful selection, commercial kits for direct radioimmunoassays of steroid hormones in postmenopausal serum can be found that may allow a reliable estimation of relative risks in epidemiological studies. However, standardization of the absolute scale of assays remains problematic.

Aged↗
PubMed1999

Breast cancer and replacement therapy: which women are at risk?

The fear of breast cancer is the most important concern for women who have to decide whether to take hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal disturbances. A calculation of the risk for breast cancer with respect to HRT is useful to reassure women about this risk and to help them to decide. In the present report, all breast cancer risk factors have been examined and those likely worsened by increased levels of estrogens with HRT have been considered. On the basis of pathogenic, clinical and epidemiological evidence seven breast risk factors (testosterone levels, body mass index, waist-to-hip ratio, alcohol consumption, density to mammography, previous benign breast disease, familiarity) have been selected and a score has been awarded to them; then a model for the calculation of the SRR (Summary Relative Risk) has been elaborated. A simple, feasible, easy to achieve decision model for the calculation of breast cancer risk is proposed in relation to the use of HRT.

Alcohol Drinking↗
PubMed1996

Serum sex hormone levels after menopause and subsequent breast cancer.

BACKGROUND: High levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer. PURPOSE: Using an improved study design, we assessed prospectively the relationship between the principal steroid sex hormones in serum and the subsequent occurrence of invasive breast cancer in postmenopausal women. METHODS: Four thousand fifty-three healthy postmenopausal women aged 40-69 years, were enrolled from June 1987 through June 1992 in a prospective investigation of hormones and diet in the etiology of breast tumors (ORDET study) as part of a larger volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese Province, northern Italy. At recruitment, blood samples were taken between 8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in -80 degree Celsius freezers. Women who had received hormone treatment in the 3 months prior to enrollment, who had bilateral ovariectomy, or who had a history of cancer or liver disease were not recruited. Twenty-five women in the final eligible cohort of postmenopausal women developed histologically confirmed, invasive breast cancer during the first 3.5 years of follow-up for the cohort (13 537 women-years). For each case subject, four control subjects were randomly chosen after matching for factors possibly affecting hormone preservation in serum. One case subject and eight control subjects were excluded because premenopausal hormonal patterns were found; thus, after also excluding the four control subjects matched to the ineligible case subject, we included 24 case and 88 control subjects. In the spring of 1994, stored sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone sulfate and estradiol (E2) by in-house radioimmunoassay and for total and free testosterone and sex hormone-binding globulin by commercially available nonextraction iodination kits. Mean differences in risk factors were tested by analysis of variance for paired data. Relative risks (RRs) were estimated by conditional logistic regression analysis. All P values resulted from two-sided tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone, and E2 were significantly higher in case subjects than in control subjects: total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone, 1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL (P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026); for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS: This prospective study provides further evidence in support of the already established association between elevated estrogen levels and breast cancer. Even more importantly, it provides new evidence that high serum testosterone levels precede breast cancer occurrence.

Adult↗
PubMed1996

Intratumour amount of sex steroids in elderly breast cancer patients. An approach to the biological characterization of mammary tumours in the elderly.

Interest in breast cancer in elderly women is growing as a result of the high frequency of cancer in older age groups. We measured tumour concentrations and circulating levels of testosterone, dihydrotestosterone (DHT) and oestradiol in 50 postmenopausal patients: 26 younger than 70 yr (median, 61.5, range 50-69) and 24 older than 70 yr (median, 74.5, range 70-82). Hormones were measured by radioimmunoassay (RIA) after extraction and separation on celite column chromatography. Intratumour levels of the three steroids were lower in the older than in the younger patients, but the difference was statistically significant only for DHT (P= 0.0126). The decrease in the tumour concentrations of testosterone and DHT in the older group was associated with a slight increase in circulating levels, yielding as final result a statistically significant decrease of the tissue/plasma (T/P) ratio of these hormones. No significant difference was observed between groups for oestradiol levels. The blood levels of testosterone, DHT and oestradiol were significantly correlated in the older group, but not in the younger group. In contrast, the tumour amounts of testosterone and DHT were found to be significantly associated only in the < 70 yr group. We concluded that the hormonal environment in which breast cancer develops is different in younger and older postmenopausal patients, and that the difference mainly concerns the intratumour amounts of androgens, suggesting that the steroids concur in the growth regulation of mammary tumours.

Age Factors↗
PubMed1996

[Treatment of prostate adenoma with finasteride. Contribution of cases].

During recent years more and more researchers and clinicians have become interested in HPB in order to identify a medical therapy instead of surgery. The aim of our study was to find the value of finasteride in HPB therapy. We wanted to know if finasteride was able to improve the symptomatology and blood tests of patients afflicted with HPB. Every patient was agreed with the course of action of the 1991 Paris Urology Congress. All patients were treated with finasteride 5 mg/die for one year and inspected by prostatic echography and blood tests. The results of our study are every interesting and are discussed in the article.

Adult↗
PubMed1995

Methods for urinary testosterone analysis.

Urinary testosterone analysis requires a multistep procedure to achieve a good degree of sensitivity and specificity in the dosage. Hydrolysis, extraction, purification and quantification are usually performed in sequence, and several options can be chosen for each of them. After introductory remarks on the applications of urinary testosterone measurement and a short description of the metabolic pathway of the hormone, an overview of the techniques most commonly used in each step is presented. Advantages and disadvantages of each of them are outlined, and a procedure for urinary testosterone analysis is suggested. The procedure consists of: enzymatic hydrolysis with Helix pomatia juice, followed by solid-phase extraction of hydrolyzed urine by a C18 cartridge coupled with an NH2 cartridge and high-performance liquid chromatography cleanup of the extract. Then, quantification can be achieved by gas chromatography or radioimmunoassay.

Chromatography, Affinity↗
PubMed1995

Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues.

The ability of breast tumours to synthesize hormones is well recognized, and local production of sex steroids is thought to play a role in breast cancer growth. We measured the intratumour and circulating levels of testosterone, dihydrotestosterone (DHT) and oestradiol in 35 histologically confirmed carcinomatous mammary tissues obtained at breast surgery from 34 postmenopausal patients, age 50-85 years. Intra-tissue steroids were extracted with ethanol:acetone (1:1; v/v), defatted with 70% methanol in water, and extracted with ether. Steroids, from tissue and serum, were separated by partition chromatography on celite columns and were measured by RIA. Intratumour testosterone and DHT concentrations were significantly correlated, after the exclusion of an outlier (rs = 0.71; P = 0.0001). No association was found between oestradiol and either of the two androgens. Mean oestradiol and DHT concentrations were significantly higher in tissue than in blood (P = 0.0001). Mean testosterone levels in tissues did not significantly differ from those measured in blood. Our data suggest that at least a part of intratissue DHT is produced locally from testosterone. The meaning of high oestradiol and DHT levels in cancer tissue still needs to be defined.

Aged↗
PubMed1994

Testosterone levels as a marker of prognosis to goserelin treatment in metastatic breast cancer.

Testosterone levels were measured in blood and urine of 35 premenopausal metastatic breast cancer patients before starting therapy with the gonadotrophin-releasing hormone (GnRH) analogue, goserelin. The aim of the study was to verify the reliability of testosterone measurement as a marker of prognosis. The time interval between starting therapy and progressive disease (time to progression) was chosen to assess prognosis. Univariate and multivariate analysis showed that only urinary testosterone levels were significantly associated with time to progression (Wald test 6.66, P = 0.01 for univariate and Wald test 7.93, P = 0.0049 for multivariate analysis), whereas no association was found for testosterone in blood. A statistical model is proposed to evaluate probability of progressive disease in relation to testosterone values in urine at different times. According to the model, the probability of progression decreases with increasing urinary testosterone values.

Adult↗
PubMed1993

Urinary testosterone as a marker of risk of recurrence in operable breast cancer.

We investigated the role of urinary testosterone levels as a marker of risk of recurrent disease in 113 operable breast cancer patients (70 premenopausal, 43 postmenopausal). Twenty-four-hour urine collections for testosterone measurement were obtained before surgical treatment, between 20-40 days thereafter, and then every 6 months for 5 years. The cutoff values to separate 'high testosterone (A+)' from 'normal testosterone (A-)' were 8.0 micrograms/24 h in premenopause and 4.9 micrograms/24 h in postmenopause. Urinary testosterone levels were considered high when they exceeded the cutoff value in at least 2 of the first 3 measurements (pretreatment, post-treatment, 6 months) of each patient. According to the aforementioned criterion, 33 patients (29.2%) had high testosterone levels, which were associated to axillary node involvement in 16 patients. Thirteen of the latter relapsed during the 5-year follow-up period (5/7 in premenopause, 8/9 in postmenopause). Relapse-free survival (RFS) curves were drawn only for node-positive patients owning to the small number of recurrences observed in the node-negative group. In premenopausal node-positive patients, RFS was significantly different for patients presenting high and normal urinary testosterone levels (77% vs 28%, respectively; logrank test, p < 0.006). In postmenopausal node-positive patients, RFS was also different between the two groups (54% vs 11% in 'high' and 'normal' excretors, respectively) but the difference was not statistically significant. The present findings suggest that urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients.

Adult↗
PubMed1992

Urinary testosterone measurement by gas chromatography after solid-phase extraction and high-performance liquid chromatography.

A method was developed for the rapid determination of testosterone in urine. The procedure consists of solid-phase extraction (SPE) followed by high-performance liquid chromatographic (HPLC) clean-up before gas chromatographic determination. Recovery was evaluated by adding [3H]testosterone (10(4) cpm) to urine samples; the mean recovery of radioactivity after SPE and HPLC was 82%. Precision was estimated by repeated measurement of testosterone in four different urine samples; the coefficient of variation was 7.9% (95% confidence limits 6.1-11.4%). Accuracy was evaluated by standard addition and dilution assays; a linear relationship was found between the expected and observed values (r2 = 0.982). The method is rapid, effective and suitable for routine analysis.

Chromatography, Gas↗