William S. Campbell

Differentiating psychiatrically disturbed children on the basis of a structured interview

A structured psychiatric interview designed for both clinical assessment and data collection was given to 50 pairs of well-matched pediatrie and psychiatric clinic children and their mothers. The two groups were shown to be dearly distinguished on the basis of numbers of symptoms. Behavior and school symptoms gave the sharpest distinction between the two groups. Neurotic and somatic symptoms were the poorest discriminators. The psychiatric children showed significantly more antisocial symptoms than their matched pediatrie peers. Age differences showed the expected trends with the widest divergence in the number of symptoms being in the oldest age group.

The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States)

We undertook a cross-sectional study in 107 premenopausal women in Maryland (United States) of alcohol intake and hormonal status in order to evaluate whether plasma hormone levels might mediate the reported positive relation between alcohol ingestion and breast cancer risk. Alcohol ingestion was estimated using a drinking pattern questionnaire, a food frequency questionnaire, and seven-day food records. Fasting blood specimens were collected on days 5–7, 12–15, and 21–23 of each participants menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Estrone, estrone sulfate, estradiol, androstenedione, and dehydropiandrosterone sulfate (DHEAS) in plasma were measured by radioimmunoassay, and sex-hormone binding globulin (SHBG) was measured by an immunoradiometric assay. After adjusting for age, weight, and total energy intake, alcohol ingestion was not associated with plasma estrogens in the follicular, midcycle, or luteal phases of the menstrual cycle, nor with the level of SHBG or DHEAS in plasma averaged from the three phases of the cycle. Alcohol, however, was significantly positively associated with the average level of plasma androstenedione. Based on these cross-sectional findings among premenopausal women, the increased risk of breast cancer related to alcohol ingestion does not appear to be mediated by elevated plasma estrogen levels. Androstenedione, however, may mediate the alcohol/breast cancer-association.

Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women.

Background: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels. Methods: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis. Results: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche <12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P < 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P > 0.10) for these five analytes beyond that of BMI alone. Conclusions: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2502–7)

The relation of body size to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States)

We analyzed data from a cross-sectional study of 107 premenopausal women to evaluate the relations of height, weight, and body mass index (BMI) with plasma hormone levels. Participants were 20- to 40-year old women residing in Maryland (United States), whose reported menstrual cycle lengths were not more than 35 days and whose measured weights for height were 85 to 130 percent of ‘desirable’ based on 1983 Metropolitan Life Insurance tables. Fasting blood specimens were collected on each of days 5–7, 12–15, and 21–23 of every participants menstrual cycle and pooled to create follicular, midcycle, and luteal phase samples, respectively, for analysis. Adjusted for age, taller women had significantly higher follicular-phase plasma-estradiol levels percent difference/cm=1.5, 95 percent confidence interval [CI]=0.3–2.7, and heavier women had significantly lower plasma sex-hormone binding globulin (SHBG) levels averaged across the menstrual cycle phases (percent difference/kg=−1.2; CI=−1.9–0.6). Body weight within the range studied, however, was not related significantly to the concentration of SHBG-bound estradiol during any phase of the menstrual cycle. The results of this cross-sectional study suggest a possible mechanism by which height may influence breast cancer risk.

Relation between sodium balance and menstrual cycle symptoms in normal women.

Women often have cyclical physical symptoms of bloating, swelling, and breast tenderness. During the luteal phase of the menstrual cycle [1, 2] and pregnancy [3], osmoregulation changes significantly [1, 2] and sodium-retaining hormone secretion [4-7] and salt preference [8] increase. The concurrence of these cyclical changes has indicated that water and sodium retention may cause physical symptoms during the luteal phase [9, 10]. If sodium is retained during the menstrual cycle, the mechanisms involved might include increased salt intake or urinary sodium retention, or both, related to the luteal phase. We hypothesized that sodium balance, a product of total sodium intake and sodium excretion, affects expression of somatic symptoms and inferred that a lower sodium intake or sodium balance should alleviate these symptoms. We therefore explored the effects of a decrease in sodium intake on the expression and severity of menstrual symptoms in women studied during three consecutive menstrual cycles. Methods Participants Thirteen healthy menstruant women without the premenstrual syndrome [10-12] (age, 21 to 35 years; weight, 50 to 80 kg; height, 160 to 180 cm) were recruited by a newspaper advertisement that requested volunteers for a diet and hormone study. Participants were taught how to complete food frequency questionnaires, collect 24-hour urine samples, and complete visual analogue scale questionnaires about the severity of menstrual symptoms [11, 12]. Study Design Diet Baseline sodium chloride intake averaged 115 23.5 mmol/d (6.7 1.3 g/d) or 2.6 1.0 g of sodium ion (Na+) per day (from food frequency records analysis, University of Minnesota Nutrition Coordinating Center, Minneapolis, Minnesota). Intake of dietary salt was then reduced by 30% (to 73.0 12.2 mmol/d [4.3 0.6 g/d]; Na+ intake, 1.6 0.2 g/d) during the next two menstrual cycles to create a moderate salt-deprivation stimulus [13]. To determine whether the use of salt depended on cycle phase, women were allowed to add salt to their food during the second month of this diet (salt-access cycle). All meals were prepared by the metabolic kitchen at the Beltsville Human Nutrition Research Center (U.S. Department of Agriculture, Beltsville, Maryland); the same menu was used every week. The use of added salt was determined from the difference in weight of packaged salt before and after each meal (each packet weighed 10 to 13 mmol [0.57 to 0.74 g]). Cycle Periods Each cycle was divided into five time periods: I = early follicular phase, days 1 to 4 (menses); II = mid-follicular phase, days 5 to 8; III = late follicular phase (luteinizing hormone surge 2 days); IV = mid-luteal phase (days 20 to 25; 7 days after the luteinizing hormone surge); and V = late luteal phase (4 days before menses). Blood specimens to determine plasma renin activity, plasma sodium levels, atrial natriuretic peptide levels, and aldosterone levels (during the 2 months of the salt-restricted diet) and two consecutive 24-hour urine samples to determine total volume, creatinine, and sodium excretion were obtained in the mid-follicular, late-follicular, and mid-luteal phases (time periods II, III, and IV, respectively) of the cycle. Luteinizing hormone levels were measured from day 11 until the luteinizing hormone surge occurred, and progesterone levels were measured 1 week after the luteinizing hormone surge. Levels of all hormones and peptides were measured by established radioimmunoassays. All samples except those of luteinizing hormone, estradiol, and progesterone were run in the same assay to avoid interassay variability. Sodium levels were measured by ion-selective electrodes. Fasting weights were obtained daily during the last 2 months of the study. Documentation of Menstrual Symptoms The visual analogue questionnaire was completed by 11 women at the same time every day for 3 months [10, 14] and was used to record ratings on questions assessing somatic symptoms and sensory cravings. Statistical Analysis A mean value was generated from the questionnaire results, body weights, and amounts of added salt (during the salt-access cycle) for the days encompassing each of the five time periods. Data were analyzed using repeated-measures analysis of variance and paired t-tests. Significance was set at a P value less than 0.05 for quantitative data and a P value less than 0.01 for symptom questionnaire scores (using the Bonferroni adjustment for interdependent questions). All expressions of variability represent the 95% CI. Data are presented as means one half of the 95% CI. Results Effects of Salt Condition Decreasing dietary sodium intake significantly altered extracellular fluid volume and sodium balance. During the first month of the salt-restricted diet (salt-restriction cycle), urinary sodium excretion decreased by 40.3 18 mmol/d from a baseline value of 115 20 mmol/d (P = 0.001) (Figure 1, top). Plasma sodium levels decreased by 0.9 0.9 mmol/L from a baseline value of 139.1 0.9 mmol/L (P = 0.018) (Figure 1, upper middle), and plasma renin activity increased by 0.14 0.08 ng/(Ls) from a baseline value of 0.25 0.08 ng/(Ls) (P = 0.008) (Figure 1, lower middle) during the 2 months of the salt-restricted diet. Levels of atrial natriuretic peptide decreased during period III of the salt-restriction cycle by 6.1 8.1 pg/mL from a mean value of 58.2 13 pg/mL in period III of the baseline cycle (P = 0.024). Figure 1. Variables measured during the baseline cycle, the salt-restriction cycle, and the salt-access cycle; during the latter, women were allowed to add salt to their food. P P Top. Bottom. P P Effects of Time of Cycle All women had ovulatory cycles during the study and equivalent estrogen and progesterone levels during each cycle. Body weight did not change significantly between or within cycles (data not shown). Plasma sodium levels were significantly lower in the luteal phase than in the follicular phase; they decreased by 1.8 1.3 mmol/L (from 140.0 0.9 mmol/L) in the baseline cycle and by 1.23 0.5 mmol/L (from 138.8 0.8 mmol/L) in the salt-restriction cycle (Figure 1, upper middle). Retention of urinary sodium was not seen in any cycle period. An increase in urinary sodium excretion of 27 16 mmol/d (from 65 10 mmol/d) was seen in period IV (mid-luteal phase) of the salt-restriction cycle (Figure 1, top). Plasma renin activity increased in the luteal phase of the baseline cycle by 0.17 0.08 ng/(mLs) from a mean value in the follicular phase of 0.19 0.08 ng/(mLs), in the luteal phase of the salt-restriction cycle by 0.25 0.17 ng/(mLs) from a mean value in the follicular phase of 0.28 0.08 ng/(mLs), and in the luteal phase of the salt-access cycle by 0.19 0.14 ng/(mLs) from a mean value in the follicular phase of 0.31 0.17 ng/(mLs) (P < 0.001) (Figure 1, lower middle). Aldosterone levels doubled in all cycles during the luteal phase (data not shown). Breast tenderness and bloating were phase dependent during all cycles studied (Figure 1, bottom). Severity ratings of swelling or bloating were higher in period I than in period II by 25 12 points (period II value, 15 11 points) in the baseline cycle, 31 15 points (period II value, 27 15 points) in the salt-restriction cycle, and 40 11 points (period II value, 15 9) in the salt-access cycle (P < 0.001) (Figure 1, bottom). These symptoms were also affected by the salt condition: Peak severity ratings were 16 19 points higher during the salt-restricted diet cycles (salt-restriction cycle and salt-access cycle) than during the baseline cycle (peak severity rating, 38 11 points; P < 0.001). Breast tenderness was most severe 4 days before menses, during which time ratings increased from the nadir of the follicular phase by 42 16 points (from 5.0 2.2 points) during the baseline cycle, by 35.0 11 points (from 10.0 11.1 points) during the first salt-restriction cycle, and by 39 6 points (from 6.0 4.4 points) during the salt-access cycle (P < 0.001). Breast tenderness was not affected by sodium balance. The highest physical comfort ratings coincided with the lowest severity ratings for breast discomfort and bloating (periods II and III). Compared with nadir ratings in the follicular phase, ratings of thirst and cravings for salt and sweets increased and peaked during the late luteal phase (time period V) (P = 0.006 for the baseline cycle, P < 0.001 for the salt-restriction cycle, and P = 0.002 for the salt-access cycle) (data not shown). In the salt-access cycle (second salt-restricted diet cycle), use of added salt was less than 10 mmol/d and did not vary with phase of the cycle (P > 0.2; data not shown). Dietary salt condition and time of cycle did not affect appetite. Discussion To study the relation between menstrual cycle symptoms and sodium balance in normal women, we changed sodium balance by decreasing intake of sodium by 30% for 2 months. This modest change in sodium balance did not decrease the severity or the cycle-dependent expression of somatic symptoms during the luteal phase or menses. We found no evidence of urinary sodium retention, and, paradoxically, sodium loss was seen during the luteal phase in the first month of the sodium-restricted diet (salt-restriction cycle), despite biochemical evidence of extracellular fluid volume contraction [13]. Although the information was not documented, we believe that natriuresis occurred during the luteal phase of the other two cycles (baseline cycle and salt-access cycle), because levels of urinary sodium excretion remained high despite elevated renin activity and aldosterone levels. Progesterone is a competitive antagonist of aldosterone [15], and high salt intake can reverse the progesterone-related increase in renin and aldosterone levels [16, 17]. These findings, together with our data, suggest that progesterone enhances natriuresis during the luteal phase in normal women and that the changes in the renin-aldosterone system during this time are probably secondary to primary natriuresis. Use

Effect of Dietary Fat on Length of the Follicular Phase of the Menstrual Cycle in a Controlled Diet Setting

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.