Trauma and amyotrophic lateral sclerosis: a case-control study from a population-based registry.

BACKGROUND AND PURPOSE: Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case-control study done in a large population. METHODS: A case-control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee. RESULTS: The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25-2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86-5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36-4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant. CONCLUSION: Antecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Highlights from "Italian Standards of care for Diabetes Mellitus 2009-2010".

The Italian Standards for the Treatment of Diabetes Mellitus represent a consensus document of the two Italian scientific diabetes societies (AMD and SID), providing specific recommendations for the diagnosis and treatment of diabetes and its complications. The level of scientific evidence behind every recommendation has been classified in accordance with the National Guidelines Plan. An original processing system was employed: the document prepared by the Editorial Team was published online for 20 days, and the suggestions and criticisms of about 30 persons were evaluated and integrated to those provided by a panel of diabetologists and members of other healthcare professions dedicated to diabetes care, as well as lay members. Lastly, the document was approved by AMD and SID National Steering Committees. In this version, some highlights of the full document (www.siditalia.it; www.aemmedi.it) concerning the main and most representative recommendations on diagnosis and treatment of diabetes and its complications as well as on diabetes care in some specific contexts, are reported.

Strongly correlated gases of Rydberg-dressed atoms: quantum and classical dynamics.

We discuss techniques to generate long-range interactions in a gas of ground state alkali atoms, by weakly admixing excited Rydberg states with laser light. This provides a tool to engineer strongly correlated phases with reduced decoherence from inelastic collisions and spontaneous emission. As an illustration, we discuss the quantum phases of dressed atoms with dipole-dipole interactions confined in a harmonic potential, as relevant to experiments. We show that residual spontaneous emission from the Rydberg state acts as a heating mechanism, leading to a quantum-classical crossover.

Supersolid droplet crystal in a dipole-blockaded gas.

A novel supersolid phase is predicted for an ensemble of Rydberg atoms in the dipole-blockade regime, interacting via a repulsive dipolar potential softened at short distances. Using exact numerical techniques, we study the low-temperature phase diagram of this system, and observe an intriguing phase consisting of a crystal of mesoscopic superfluid droplets. At low temperature, phase coherence throughout the whole system, and the ensuing bulk superfluidity, are established through tunnelling of identical particles between neighboring droplets.

[Firearms related suicide/homicide rate among the security guards population in Italy]. / Suicidi e omicidi con l'arma di ordinanza. Analisi della casistica nelle guardie particolari giurate in Italia.

OBJECTIVE: The main aim of this study is evaluating the suicide/homicide rate of the Italian security guards population compared to other armed and general populations during a recent period. METHODS: The authors reviewed the incidence of suicides and homicides among security guards from 1996 to 2006 and, where information was available, a comparison was made with Italian population adapted by age. Comparisons with the general population were also made. RESULTS: The average rate of firearms related suicide among the security guards population during the established period was 11.7 per 100,000 persons-years (95% CI = 6.6-16.7) compared to a guns-related suicide rate of 0.7 per 100,000 person-years, (95% CI = 0.6-0.7) and a non-guns related rate of 5.5 per 100,000 persons-years, (95% CI = 5.2-5.9) for the general population adjusted for age. The overall homicide rate among security guards during the period was 11.4 per 100,000 person-years (95% CI = 6.2-15.4) compared with the homicide rate for the Italian population of 5.4 per 100,000 persons-years, (95% CI = 7.3-15.4). CONCLUSION: The rate of suicide and homicide among the Italian security guards population was higher than the suicide/homicide rate in the general population. These results show that the phenomenon we have described needs attention and specific prevention activities.

[Electrical manifestations of dead myocardium associated to proximal blocks of intermediate degree]. / Aspectos eléctricos de la asociación de miocardio inactivable y bloqueos tronculares de grado intermedio.

The electrical manifestation of dead myocardium associated to incomplete bundle branch block, i.e., with a limited "jumping wave" phenomenon, are exposed. Our description is based on previous experimental studies and validated by electro-anatomical comparisons. In previous experimental reports, the electrical manifestations of dead myocardium in the presence of varying degrees of associated block have also been described. The main electrocardiographic changes are related to the location and extent of damaged region and to degree of bundle branch block. If a left bundle branch block coexists with dead myocardium, small Q waves are registered in left unipolar leads exploring the damaged area. In these leads, the signs of subepicardial or transmural injury are increased. When a right proximal block coexists, the main changes concern the morphologies registered in the unipolar right epicardial and precordial leads. The electrical changes are due to the spatial orientation of the electromotive forces of ventricular depolarization and repolarization. The electrocardiographic changes described here can be satisfactorily understood in the light of the present knowledge on the ventricular electrical phenomenon.

Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders.

BACKGROUND: The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown. METHODS: Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002-2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan-Meier survival/failure function and C statistics. RESULTS: A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS-). Relative to ARMS-, the ARMS+ was associated with an increased risk (HR=4.825) of developing psychotic disorders, and a reduced risk (HR=0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P<0.001). CONCLUSIONS: In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes. SIGNIFICANT OUTCOMES: In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup. LIMITATIONS: While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.

Estimating regional cancer burden in countries with partial registration coverage: an application to all malignant neoplasms in Italy over the period 1970-2010.

Regional epidemiological indicators of cancer burden are essential information for cancer surveillance and health resources planning, especially in countries with partial registration coverage and geographically variable risk patterns, such as Italy. This paper presents a methodology to derive cancer incidence and prevalence at the regional and national scale and illustrates its application to all malignant neoplasms in Italy for the period 1970-2010. The method, denoted as MIAMOD, is based on a back-calculation approach and derives cancer-specific morbidity measures by using official mortality data and model-based relative survival from local Cancer Registries data. The output includes time-trends and projections of a complete set of epidemiological indicators, i.e. mortality, incidence and prevalence. Results for all cancers in Italy show different incidence patterns by gender and a pronounced regional variability among men: male incidence is estimated to decrease in almost all northern-central regions, while more stable or even rising trends are estimated in the southern regions. No incidence reduction is expected for women. Prevalence increases country-wide in both sexes. The proposed approach can be applied to derive regional up-to-date time trends of cancer burden indicators in countries with local and sparse cancer registration systems. These estimates are useful for planning health services on a national and regional basis and for highlighting regional differences.

Reliability of urinary 6-sulfatoxymelatonin as a biomarker in breast cancer.

The objective of this study is to evaluate the effect of cryopreservation at different storage temperatures on urinary 6-sulfatoxymelatonin (aMT6s) concentration. Overnight urine from 28 postmenopausal women participating in the ORDET cohort study was filtered and separated into 6 mL aliquots. Urine samples were stored at -80 degrees C and at -30 degrees C for an average of 14 years. Urinary aMT6s concentration was assessed using a competitive immunoassay. Mean aMT6s values of samples stored at -30 degrees C were systematically lower than those of samples stored at -80 degrees C (10.7 ng/mL versus 15.8 ng/mL, p<0.001). Bland Altman plots showed disagreement between determinations at different storage temperatures at the highest levels of the metabolite concentration. The degree of agreement evaluated in terms of intraclass correlation coefficient was 0.68 (95% CI 0.41-0.84, p<0.0001). Pearson's correlation coefficient between aMT6s values of the two differently stored samples was 0.93 (p<0.001), while the Kendal tau coefficient for rank distribution was 0.73 (p<0.001). Our data suggest that storage temperatures might affect degradation of aMT6s during storage. However, individual characterization by melatonin levels does not seem to be affected by cryopreservation conditions.

Diffuse large B-cell lymphoma involving the breast. A report of four cases.

Non-Hodgkin lymphoma of the breast is an uncommon form of lymphoma occurring either primary disease (PBL) or part of systemic involvement. We report the clinical outcome of 4 consecutive cases with CD20+ diffuse large B-cell lymphoma (DLBCL) of the breast, in the attempt to further clarify the management of this disease. The median age was 53 years (39-61), stages were IIE (n=2), IIIE (n=1), and IV (n=1); IPI scores were 0 (n=2), 2 (n=2). Two cases were PBL, and 2 were secondary involvement of the breast. Two stage IIE patients received MACOP-B, radiation therapy was given to one of them and both achieved CR. The stage IIIE patient treated with MACOP-B plus Rituximab was in PR at the beginning of the Rituximab and achieved CR at the end of the treatment. The 61-year-old stage IV patient and bilateral involvement received P-VNBEC as first line treatment, achieving PR; she was then treated with 4 cycles of MACOP-B plus Rituximab obtaining CR. After a median follow-up of 40 months (31-50) all patients are alive and in CR. No CNS prophylaxis was given and no incidence of CNS relapse was observed. In our experience DLBCL of the breast shows chemosensitivity to MA-COP-B regimen but the intensification with Rituximab seems to be effective especially in the advanced stages. Further and comparative studies are required to confirm the validity of our results.

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.

Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management.

BACKGROUND: Surgical removal of axillary lymph node and histologic examination for metastases are used to determine whether adjuvant treatment is necessary for patients with breast cancer. Axillary lymph node dissection (ALND) is a costly procedure associated with various side effects, and 80% or more of patients with tumors of 20 mm or less are lymph node negative and might avoid ALND. In this study, we evaluated whether an alternative, noninvasive method--i.e., positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be used to determine axillary lymph node status in patients with breast cancer. METHODS: One hundred sixty-seven consecutive patients with breast cancers of 50 mm or less (range = 5-50 mm; mean = 21 mm) scheduled for complete ALND were studied preoperatively with FDG-PET, and then PET and pathology results from ALND were compared. All statistical tests were two-sided. RESULTS: The overall sensitivity, specificity, and accuracy of lymph node staging with PET were 94.4% (PET detected 68 of 72 patients with axillary involvement; 95% confidence interval [CI] = 86.0% to 98.2%), 86.3% (82 of 95 patients without axillary involvement; 95% CI = 77.8% to 91.9%), and 89.8% (150 of 167 patients with breast cancer; 95% CI = 84.2% to 93.6%), respectively. Positive- and negative-predictive values were 84.0% (68 patients with histologically positive lymph nodes of 81 patients with positive FDG-PET scan; 95% CI = 74.2% to 90.5%) and 95.3% (82 patients with histologically negative lymph nodes of 86 patients with negative FDG-PET scan; 95% CI = 88.2% to 98.5%), respectively. When PET results for axillary metastasis were analyzed by tumor size, the diagnostic accuracy was similar for all groups (86.0%-94.2%), with higher sensitivity for tumors of 21-50 mm (98.0%) and higher specificity for tumors of 10 mm or less (87.8%), and the range was 93.5%-97.3% for negative-predictive values and 54.5%-94.1% for positive-predictive values. Among the 72 patients with axillary involvement, PET detected three or fewer metastatic lymph nodes in 27 (37.5%) patients, about 80% of whom had no clinically palpable axillary lymph nodes. CONCLUSIONS: Noninvasive FDG-PET appears to be an accurate technique to predict axillary status in patients with breast cancer and thus to identify patients who might avoid ALND. These results should be confirmed in large multicenter studies.

Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study.

BACKGROUND: The relationship between erythrocyte membrane fatty acids and postmenopausal breast cancer risk was analyzed previously only by retrospective studies, which suggested a protective effect of increased saturation index (SI), i.e., the ratio of membrane stearic to oleic acid. We investigated the relationships in a prospective study of hormones, diet, and prediagnostic breast cancer (the ORDET study) conducted in northern Italy. METHODS: A total of 4052 postmenopausal women were followed for an average of 5.5 years; 71 cases of invasive breast cancer were identified. For each case subject, two matched control subjects were chosen randomly from among cohort members. The various fatty acids in erythrocyte membranes were measured as a percentage of total fatty acids. Conditional logistic regression analysis evaluated the association between membrane fatty acid composition and breast cancer risk. The SI, which is influenced by the activity of the enzyme delta 9 desaturase (Delta 9-d), was also investigated. All statistical tests were two-sided. RESULTS: Oleic (highest versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer risk, but individual polyunsaturated fatty acids behaved differently. There was no association between saturated fatty acids and breast cancer risk. CONCLUSIONS: We have found that monounsaturated fats and SI in erythrocyte membranes are predictors of postmenopausal breast cancer. Both of these variables depend on the activity of the enzyme Delta 9-d. The dietary, metabolic, and hormonal factors acting on Delta 9-d expression and activity and, therefore, on patterns of fatty acid metabolism, should be further investigated as possible determinants of breast cancer.

[On the electrical manifestations of some heart diseases associated with ventricular preexcitation]. / Manifestaciones eléctricas de alteraciones miocárdicas asociadas a preexcitación ventricular.

Electro-Vectorcardiographic curves, corresponding some heart diseases, must be analyzed in the light of the ventricular depolarization sequence, as well as on the heart's position and rotation. A more than 30-msec interval between the end of the initial slurring (delta) and the vertex of the R wave in the left unipolar leads or the main axis of the vectorcardiographic ventricular curves, allows us to infer the coexistence of left ventricular hypertrophy. On the other hand, segmental irregularities or distorsions of the electric curves suggest the presence of a limited myocardial zone unable to be activated. Extensive or multiple deformations of these curves are more suggestive of a diffuse myocardial damage. Sometimes signs of preexcitation, due to a pharmacological action, can also appear.

Biological parameters and the segregation distortion (SD) phenomenon in Drosophila melanogaster.

The relationship between some biological parameters (mortality, longevity, fertility, fecundity and sex ratio) and segregation of second chromosomes in heterozygous and homozygous SD males has been analyzed. The results obtained in SD/SD+ heterozygous males show: (1) their reduced fertility with respect to that of control males, (2) an alteration in the sex ratio in the SD+ progeny only, and (3) inversely related sex-ratio and segregation distortion values. In SDi/SDj combinations: (1) surprisingly, fertility is intermediate between that of SD/SD+ heterozygous males and that of control males, (2) the segregation ratios of the second chromosomes are normal (0.50), and (3) the sex ratio = 0.50 in both classes of SD progeny. The relationship between mortality (and therefore longevity) and fertility of the different genotypes and fecundity per male indicates that the total productivity of heterozygous males is less than that so far claimed. Indeed, their productivity depends not only on the mechanism of nonformation of the SD+ sperm, but also on their reduced longevity. The k = 0.50 and the high fecundity of SDi/SDj combinations indicated that in these males the SD phenomenon is partially suppressed, the SD chromosomes being insensitive to each other, thus implying that particular Rsp alleles are sensitive to given Sd alleles. The complementation pattern for male fertility of SD homozygous males again supports previous evidence that Sd factors from natural populations are, in effect, different Sd genes.

Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease.

In recent years, substantial investigative attention has focused on therapeutic regimens that could retard the progression of chronic renal insufficiency. Emphasis has been placed on the effects of antihypertensive treatment on renal hemodynamics and preservation of renal function. It has been suggested that some classes of antihypertensive agents may confer a greater renoprotective effect, especially agents that lower glomerular capillary pressure. Conversely, by virtue of their ability to preferentially dilate the afferent arteriole calcium antagonists theoretically could favor an increase in glomerular capillary pressure thereby accelerating the decline of renal function. In this review we survey the literature critically and conclude that in patients with essential hypertension and in patients with chronic renal insufficiency, calcium antagonists effectively reduce systemic blood pressure while maintaining glomerular filtration rate and effective renal plasma flow. Preliminary results from a few long-term studies suggest that calcium antagonists may even attenuate the decline in renal function of patients with chronic renal failure. The majority of studies in humans, however, have been nonrandomized, of too short duration, or confounded by investigative difficulties precluding definite conclusions whether calcium antagonists have renoprotective effects. Although the possibility that calcium antagonists may retard progression of renal disease remains to be ascertained, the available evidence indicates that calcium antagonists may be used in patients with renal functional impairment without further exacerbating renal function.

Validity for epidemiological studies of long-term cryoconservation of steroid and protein hormones in serum and plasma.

Prospective studies based on the storage of biological samples at low temperature have opened new perspectives in etiological research on cancer. In planning these studies a crucial question is to evaluate whether the long-term preservation of samples is able to affect the categorization of the subjects involved. In the frame of the ORDET project, a prospective study of hormones and diet in the etiology of breast cancer provided with a -80 degrees C biological bank, we have evaluated the stability of estradiol, free and total testosterone, and prolactin in serum and plasma samples over 3 years of cryoconservation. Study results showed that the subjects maintained almost the same rank by hormonal concentration throughout the 3-year period for all hormones. Looking at the stability over time, estradiol, prolactin, and total testosterone had fairly good performance for both serum and plasma. Serum-free testosterone increased in time up to 30%, whereas progesterone decreased by about 40% of the initial concentration. However, the reliability of the individual categorization by hormonal level suggests the validity of low temperature storage for epidemiological purposes, at least for hormonal parameters.

Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period.

Serum hormones have been intensively investigated in association with several chronic diseases, but limited information exists on the reliability of a number of hormone determinations. The one-year reproducibility of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone, total estradiol, insulin, C-peptide, and prolactin was studied in 60 premenopausal and 47 postmenopausal women recruited in Varese province, Italy, 1991-1992. The hormonal determinations were made in blood samples collected twice, one year apart, after 12-h fast, in the same month, day, and hour and for premenopausal women on the same day of the luteal phase of the menstrual cycle. Samples from the first drawing were stored at -80 degrees C. Samples from both drawings were assayed simultaneously and in blind fashion. Total estradiol in postmenopause was not evaluated for limitation in the sensitivity of the laboratory method. The intraclass correlation coefficient in premenopausal women was 0.85 for DHEAS, 0.60 for total testosterone, 0.66 for free testosterone, 0.81 for insulin, 0.83 for C-peptide, 0.40 for prolactin, and 0.06 for total estradiol. In postmenopausal women, the coefficient was 0.90 for DHEAS, 0.88 for total testosterone, 0.71 for free testosterone, 0.67 for insulin, 0.73 for C-peptide, and 0.18 for prolactin. These data indicate that total estradiol measured during the luteal phase has a poor intraindividual reproducibility over time, and these findings may have important implications in studies of hormones in the etiology of chronic disease.