Selected food intake and risk of endometriosis.

BACKGROUND: To offer data on the relationship between diet and risk of pelvic endometriosis, we analysed data collected in the framework of two case-control studies. METHODS: Data from two case-control studies conducted in Northern Italy between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of endometriosis, admitted to a network of obstetrics and gynaecology departments in Milan, Brescia and Pavia. Controls were 504 women (median age 34 years, range 20-61) admitted for acute non-gynaecological, non-hormonal, non-neoplastic conditions. RESULTS: Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for higher intake of green vegetables [odds ratio (OR) = 0.3 for the highest tertile of intake] and fresh fruit (OR = 0.6), whereas an increase in risk was associated with high intake of beef and other red meat (OR = 2.0) and ham (OR = 1.8). Consumption of milk, liver, carrots, cheese, fish and whole-grain foods, as well as coffee and alcohol consumption, were not significantly related to endometriosis. CONCLUSIONS: This study suggests a link between diet and risk of endometriosis.

Risk factors for different histological types of ovarian cancer.

Various histological types of ovarian cancer may develop from different etiological aspects. Data separated by histological subtypes collected in the framework of a large case-control study on ovarian cancer conducted in Italy were analyzed. The cases were women below the age of 75 years, admitted to a network of hospitals in Milan. Cases were grouped into four categories by histological type: mucinous tumor (n = 52), serous tumor (n = 680), endometrioid tumor (n = 41), and other histologies including clear-cell and undifferentiated epithelial tumors (n = 50). Controls were 2758 patients admitted to the same network of hospitals for a wide spectrum of acute, nongynecological, non-hormone-related, non-neoplastic conditions. In comparison with nulliparae, the risk of serous, endometrioid, and other histologies of ovarian cancer tended to be lower in parous women, but the odds ratios (OR) were above unity for mucinous ovarian cancer. Oral contraceptive use was associated with OR lower than unity for serous (OR = 0.7) and endometrioid (OR = 0.8) ovarian cancers but not for mucinous (OR = 1.4) and other histologies (OR = 1.6). Finally, our results on dietary fat intake did not show substantial differences in all histological types of ovarian cancer.

Moderate alcohol drinking and risk of preterm birth.

OBJECTIVE: We have analysed the association between alcohol drinking before and during the three trimesters of pregnancy and risk of preterm birth of babies with normal weight for gestational age or with low weight for gestational age (SGA). DESIGN: Case-control study. SETTING: General and university hospitals in Italy. SUBJECTS: Cases were 502 women who delivered preterm births <37 weeks gestation. The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight (ie between 10th and 90th centile according to the Italian standard) on randomly selected days at the hospitals where cases had been identified. INTERVENTIONS: Interview. RESULTS: No increased risk of preterm birth was observed in women drinking one or two drinks/die in pregnancy, but three or more drinks/die increased the risk (multivariate odds ratios (OR) 2.0 for >/=3 drinks during the first trimester, 1.8 during the second and 1.9 during the third). When the analysis was conducted separately for preterm births with normal weight or SGA, the increased risk was observed in preterm SGA only (multivariate OR for >/=3 drinks/die during the first trimester=3.6, 95% confidence interval (CI) 1.3-11.1); the estimated multivariate OR for >/=3 drinks/die during the first trimester of preterm babies with normal weight for gestational age was only slightly above unity and not statistically significant (multivariate OR 1.4, 95% CI 0.5-3.7). CONCLUSIONS: The study shows an increased risk in mothers who drink >/=3 die units alcohol in pregnancy of preterm births.

Risk factors for endometrial hyperplasia: results from a case-control study.

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35-73 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990-99 were examined. Controls were 258 non hysterectomized women aged 36-74 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related. Cases with EH were more educated than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7-4.8), more frequently obese (OR 2.7, 95% CI 1.5-5.0) and diabetic (OR 2.4, 95% CI 0.8-6.9). Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an increased risk of EH, but the associations were not statistically significant. Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1-0.5) for postmenopausal ones. Compared to women reporting menopause at age 50 or less, the OR of endometrial hyperplasia was 1.5 (95% CI 0.6-3.5) and 2.2 (95%CI 0.7-6.7), respectively, in women with menopause at age 50-52 and > or = 53. Considering postmenopausal women only the OR was 3.1 (95% CI 1.1-9.3) for use of hormonal replacement therapy (HRT). We conclude that this study indicates that high education, obesity, diabetes, and HRT use increase the risk of endometrial hyperplasia.

Time since last birth and the risk of ovarian cancer.

OBJECTIVES: While parity is a protective factor in ovarian cancer, the role of time factors of pregnancy and birth is still controversial. We considered therefore the role of birth timing in the risk in ovarian cancer from a large case-control study. METHODS: Cases were 971 women (age range 22-74 years, median age 54) with histologically confirmed, incident epithelial ovarian cancer, interviewed between 1983 and 1991 in a network of hospitals in Milan, Italy. Controls were 2758 women (age range 23-74 years, median age 52) admitted to the same hospitals where cases were identified for acute, nonneoplastic conditions. RESULTS: In comparison with nulliparous women, the multivariate odds ratios (OR) were 0.8 for women reporting one or two and 0.6 for those with three or more births. No clear association emerged between time since last birth and ovarian cancer. Compared to women who had last given birth since > or =20 years, a moderately increased risk of ovarian cancer was observed in the first 10 years after last birth, with an OR of 1.7 (95% confidence interval, CI 1.0-2.9). When we considered only multiparous women and included in the multivariate analysis allowance for age at first birth, the OR decreased to 1.2 (95% CI 0.6-2.4). No consistent pattern of trends was observed > or =10 years since last pregnancy. CONCLUSIONS: This study confirms the protective effect of parity on ovarian carcinogenesis, but shows no consistent pattern of risk across time since last birth.

Creatine as nutritional supplementation and medicinal product.

Because of assumed ergogenic effects, the creatine administration has become popular practice among subjects participating in different sports. Appropriate creatine monohydrate dosage may be considered a medicinal product since, in accordance with the Council Directive 65/65/EEC, any substance which may be administered with a view to restoring, correcting or modifying physiological functions in humans beings is considered a medicinal product. Thus, quality, efficacy and safety must characterise the substance. In addition, the European Court of Justice has held that a product which is recommended or described as having preventive or curative properties is a medicinal product even if it is generally considered as a foodstuff and even if it has no known therapeutic effect in the present state of scientific knowledge. In biochemical terms, creatine administration increases creatine and phosphocreatine muscle concentration, allowing for an accelerated rate of ATP synthesis. In thermodynamics terms, creatine stimulates the creatine-creatine kinase-phosphocreatine circuit, which is related to the mitochondrial function as a highly organised system for the control of the subcellular adenylate pool. In pharmacokinetics terms, creatine entry into skeletal muscle is initially dependent on the extracellular concentration, but the creatine transport is subsequently downregulated. In pharmacodynamics terms, the creatine enhances the possibility to maintain power output during brief periods of high-intensity exercises. In spite of uncontrolled daily dosage and long-term administration, no researches on creatine monohydrate safety in humans were set up by standardised protocols of clinical pharmacology and toxicology, as currently occurs in phases I and II for products for human use. More or less documented side effects induced by creatine monohydrate are weight gain; influence on insulin production; feedback inhibition of endogenous creatine synthesis; long-term damages on renal function. A major point that related to the quality of creatine monohydrate products is the amount of creatine ingested in relation to the amount of contaminants present. During the industrial production of creatine monohydrate from sarcosine and cyanamide, variable amounts of contaminants (dicyandiamide, dihydrotriazines, creatinine, ions) are generated and, thus, their tolerable concentrations (ppm) must be defined and made consumers known. Furthermore, because sarcosine could originate from bovine tissues, the risk of contamination with prion of bovine spongiform encephalopathy (BSE or mad-cow disease) can t be excluded. Thus, French authorities forbade the sale of products containing creatine. Creatine, as other nutritional factors, can be used either at supplementary or therapeutic levels as a function of the dose. Supplementary doses of nutritional factors usually are of the order of the daily turnover, while therapeutic ones are three or more times higher. In a subject of 70 kg with a total creatine pool of 120 g, the daily turnover is approximately of 2 g. Thus, in healthy subjects nourished with fat-rich, carbohydrate, protein-poor diet and participating in a daily recreational sport, the oral creatine monohydrate supplementation should be of the order of the daily turnover, i.e., less than 2.5-3 g per day, bringing the gastrointestinal absorption to account. In healthy athletes submitted daily to high-intensity strength or sprint training, the maximal oral creatine monohydrate supplementation should be of the order of two times the daily turnover, i.e., less than 5-6 g per day for less than two weeks, and the creatine monohydrate supplementation should be taken under appropriate medical supervision. The oral administration of more that 6 g per day of creatine monohydrate should be considered as a therapeutic intervention and should be prescribed by physicians only in the cases of suspected or proven deficiency, or in conditions of severe stress and/or injury. The incorporation of creatine into the medicinal product class is supported also by the use in pathological conditions, e.g., some mitochondrial cytopathies, the guanidinoacetate methyltransferase deficiency, etc.

Dietary factors and risk of spontaneous abortion.

OBJECTIVE: This study examines the association between dietary habits and risk of spontaneous abortion. DESIGN: Hospital-based case-control study. SETTING: Obstetric hospitals in Milan, Italy. SUBJECTS: Cases were: 912 women admitted for spontaneous abortion (within the 12th week of gestation). Controls were: women who gave birth at term to healthy infants on randomly selected days at the same hospitals where cases had been identified. RESULTS: The risk of spontaneous abortion was inversely and significantly related to green vegetables, fruit, milk, cheese, eggs and fish consumption. The multivariate odds ratios (OR), for highest versus lowest levels of intake, were 0.3 for fruit, 0.5 for cheese, 0.6 for green vegetables and milk and 0.7 for fish and eggs. The major type of seasoning fats have showed a direct association with risk of miscarriage. Comparing the highest with the lowest intake, the ORs were 2.0 (95% confidence interval, CI 1.1-3.6) and 1.6 (95% CI 1.1-2.3) for butter and oil, respectively. No consistent association emerged between meat, liver, ham and carrots intake and the risk of spontaneous abortion. CONCLUSIONS: This result suggests that a diet poor in several aspects, including vegetables and fruit, milk and dairy products, but rich in fats, may be a determinant or a correlate of increased risk of spontaneous abortion.

Selected food intake and risk of multiple pregnancies.

In order to explore the association between multiple birth risk and diet, data were analysed from a case-control study on risk factors for multiple births conducted in Italy between 1988 and 1998. A total of 185 cases (median age 30 years) were interviewed: 36 women delivered monozygotic and 149 delivered spontaneous dizygotic multiple births. The control group comprised 498 women who gave birth at term (>37 weeks gestation) to healthy infants on randomly selected days at the same clinic. Women were specifically excluded if they reported a history of multiple pregnancy or they had received treatment for infertility for the index pregnancy. No marked differences emerged in daily intake between cases and controls and a total of 35 foods items, including the major sources of beta-carotene, retinol, ascorbic acid, vitamin D, E, methionine folate and calcium in the Italian diet. Likewise intake of selected micronutrients was largely similar in dizygotic cases, monozygotic cases and controls, with the only exception of a slightly lower intake of folates in dizygotic pregnancies in comparison with controls: this difference was statistically significant (P < 0.05), but limited in quantitative terms (mean daily intake of folate 192.4, 183.2 and 191.4 microg respectively in monozygotic, dizygotic cases and controls). In conclusion, the results of this study do not support the role of diet in the development of multiple births.

Influence of menstrual and reproductive factors on ovarian cancer risk in women with and without family history of breast or ovarian cancer.

BACKGROUND: As women with a family history of ovarian and/or breast cancer possibly inherit genetic changes that alter their risk of ovarian cancer, other established risk factors for ovarian cancer may influence the risk differently in women with and without a family history of the disease. METHODS: Case-control study conducted between 1983 and 1991 in Northern Italy. Cases were 971 women, under 75 years, with incident, histologically confirmed epithelial ovarian cancer, and controls were 2758 women, under 75 years, admitted to hospitals for non-malignant, non-hormone-related conditions, who had not undergone bilateral oophorectomy. Of these, 93 cases and 139 controls had a family history of ovarian and/or breast cancer. RESULTS: The risk of ovarian cancer increased with irregular menstrual cycles, late age at menopause, natural menopause, nulliparity, never use of oral contraceptives and use of hormone replacement therapy. We computed an 'adult life risk score' (ALRS) considering the combined effect of these factors. Compared to women without a family history and a low ALRS, the OR was 1.7 for women without family history and high ALRS, 1.4 for women with a family history and low ALRS, and 3.5 for women with a family history and high ALRS. CONCLUSIONS: Intervention on selected hormonal risk factors for ovarian cancer might be important for women with a family history of the disease.

Risk factors for urinary incontinence in women.

OBJECTIVES: To review the epidemiological evidence on risk factors for urinary incontinence (UI) in women. METHODS: Using Medline and a manual search we identified the main papers published in English up to 1998. RESULTS: There is consistent evidence that the frequency of UI increases with age, but there is little information on the frequency of different types of UI in different age groups. With regard to other risk factors, there is a clinical consensus that vaginal delivery and, more in general, obstetric traumas are associated with UI, although epidemiological studies are not always consistent. Less defined is the role of race, menopausal status, history of gynecological surgery, body mass index, smoking, and coffee and alcohol consumption on the risk of UI. CONCLUSION: In the coming years, epidemiological research should focus particularly on the potential differences in the epidemiological characteristics of different types of UI in order to gain insight into the pathogenic mechanisms.

Population attributable risk for ovarian cancer.

Parity, oral contraceptive (OC) use, age at menopause, a family history of the disease and selected aspects of diet have been related to the risk of ovarian cancer. The quantification of their impact on a population level may help focus and rank the importance of potential prevention strategies. Using data from a case-control study conducted in Italy between 1983 and 1991 on 971 ovarian cancer cases and 2758 control women we computed the multivariate relative risk estimates, and population attributable risks (PARs), i.e. the proportion of ovarian cancers that would have been avoided if a given exposure had not been present in the population. Overall, the PARs were 5% for nulliparity, 12% for never OC use and 4% for a family history of breast or ovarian cancer in first-degree relatives. Among women aged >/=50 years, later age at menopause accounted for 16% of all ovarian cancer cases. Low intake of green vegetables accounted for 24% of cases and a high fat score for 7%. All these factors together explained 51% of cases. In conclusion, even if the PAR estimates were based on several arbitrary assumptions, available knowledge could, in principle, explain over 50% of all ovarian cancer cases in this Italian population, thus indicating and quantifying the theoretical scope for prevention.

Is there a rationale for the use of creatine either as nutritional supplementation or drug administration in humans participating in a sport?

Even though no unambiguous proof for enhanced performance during high-intensity exercise has yet been reported, the creatine administration is charged to improve physical performance and has become a popular practice among subjects participating in different sports. Appropriate creatine dosage may be also used as a medicinal product since, in accordance with the Council Directive 65/65/CEE, any substance which may be administered with a view to restoring, correcting or modifying physiological functions in human beings is considered a medicinal product. Thus, quality, efficacy and safety must characterize the substance. In biochemical terms, creatine administration enhances both creatine and phosphocreatine concentrations, allowing for an increased total creatine pool in skeletal muscle. In thermodynamics terms, creatine interferes with the creatine-creatine kinase-phosphocreatine circuit, which is related to the mitochondrial function as a highly organized system for the energy control of the subcellular adenylate pool. In pharmacokinetics terms, creatine entry into skeletal muscle is initially dependent on the extracellular concentration, but the creatine transport is subsequently down-regulated. In pharmacodynamics terms, the creatine enhances the possibility to maintain power output during brief periods of high-intensity exercises. In spite of uncontrolled daily dosage and long-term administration, no research on creatine safety in humans has been set up by specific standard protocol of clinical pharmacology and toxicology, as currently occurs in phase I for the products for human use. More or less documented side effects induced by creatine are weight gain; influence on insulin production; feedback inhibition of endogenous creatine synthesis; long-term damages on renal function. A major point that related to the quality of creatine products is the amount of creatine ingested in relation to the amount of contaminants present. During the production of creatine from sarcosine and cyanamide, variable amounts of contaminants (dicyandiamide, dihydrotriazines, creatinine, ions) are generated and, thus, their tolerable concentrations (ppm) must be defined by specific toxicological researches. Creatine, as the nutritional factors, can be used either at supplementary or therapeutic levels as a function of the dose. Supplementary doses of nutritional factors usually are of the order of the daily turnover, while therapeutic ones are three or more times higher. In a subject with a body weight of 70 kg with a total creatine pool of 120 g, the daily turnover is approximately 2 g. Thus, in healthy subjects nourished with a fat-rich, carbohydrate-, protein-poor diet and participating in a daily recreational sport, the oral creatine supplementation should be on the order of the daily turnover, i.e. less than 2.5-3 g per day, bringing the gastrointestinal absorption to account. In healthy athletes submitted daily to high-intensity strength- or sprint-training, the maximal oral creatine supplementation should be on the order of two times the daily turnover, i.e. less than 5-6 g per day for less than 2 weeks, and the creatine supplementation should be taken under appropriate medical supervision. The oral administration of more than 6 g per day of creatine should be considered as a therapeutic intervention because the dosage is more than three times higher than the creatine daily turnover and more than six times higher than the creatine daily allowance. In this case, creatine administration should be prescribed by physicians only in the cases of suspected or proven deficiency, or in conditions of severe stress and/or injury. 2000 Academic Press@p$hr

Correlates of hormone replacement therapy use in Italian women, 1992-1996.

OBJECTIVES: we analyzed the determinants of hormonal replacement therapy (HRT) use in Italy for the period 1992-1996, using data from a framework of case-control studies of colon and rectal neoplasm. METHODS: a total of 1574 women aged 45-74 years were considered. This group comprised women with acute, non neoplastic, non-hormone-related diseases admitted to a network of hospitals in six areas of Italy. RESULTS: a total of 146 women (8.5%) reported ever HRT use. The multivariate odds ratio (OR) of ever use was 1.6 (95% CI 1.0-2.6) for women with 12 years of education or more, compared with those with < 7 years. The frequency of use of HRT tended to decrease with increasing parity: the OR was 0.6 for women with four or more children as compared to nulliparae (chi2 trend 3.5, P = 0.06). Ever HRT users were more frequently smokers. HRT use was more frequent in women reporting surgical menopause (OR = 2.7) than those with natural menopause. Among post menopausal women, HRT use was related with early age at menopause (chi2 trend 4.6, P = 0.03). HRT use was more common among women reporting lower body mass index (BMI) both at interview and at age 30 years and the difference between current BMI and BMI at age 30 years, was not related with HRT use. CONCLUSIONS: women of higher socioeconomic status or education reported more frequent HRT use and nulliparae and smokers were also more likely to use HRT. Further HRT use was directly associated with early age at menopause and surgical menopause and inversely related with measures of body weight.

Diabetes and endometrial cancer: an Italian case-control study.

We considered the association between diabetes and risk of endometrial cancer using data from a large case-control study conducted in Italy. Cases were 752 women with incident, histologically confirmed endometrial cancer < 75 years of age (median age 60 years, range 28-74) admitted to a network of hospitals in Milan. Controls were 2,606 patients (median age 54 years, range 25-74) aged < 75 years, admitted for acute non-neoplastic, non-gynecological, non-hormone-related conditions to the same network of hospitals where cases had been identified. A total of 132 (17.6%) cases and 116 controls (4.5%) reported a history of diabetes. The corresponding multivariate odds ratio (OR) was 2.9 [95% confidence interval (CI) 2.2-3.9]. No association emerged with diabetes diagnosed under age 40 (likely to be insulin-dependent diabetes), whereas the OR of endometrial cancer was 3.1 (95% CI 2.3-4.2) for diabetes diagnosed at age > or = 40 years. The OR of endometrial cancer in women with history of diabetes was 3.0 for women with a body mass index (BMI) (QI) kg/m2 < 25, 3.6 for those with a BMI of 25-29, and 3.3 for those with a BMI > or = 30. No consistent interaction or modifying effect was observed for any other covariate. Our results confirm that non-insulin-dependent diabetes is associated with the risk of endometrial cancer. The association may be mediated through elevated oestrogen levels in diabetic women, hyperinsulinemia or insulin-like growth factor-I (IGF-I).

The epidemiology of multiple births.

On the basis of MEDLINE and manual searches, we examined the main papers in the English literature regarding risk factors for spontaneous (i.e. not related to fertility drug use) multiple births. The constant frequency of monozygotic (MZ) pregnancies over time and in different geographical areas suggests that the determination of MZ twins is largely unchanged over time, and that a genetic mechanism may have a role. In contrast, temporal and geographical trends observed in dizygotic (DZ) pregnancies suggest that environmental factors play a role in determining this condition. At present, maternal age and hereditary components are the best-defined determinants for spontaneous multiple births.