Grapefruit juice and the response to warfarin.

The effect if any of prepared frozen grapefruit juice on prothrombin times (PTs) in patients undergoing stabilized warfarin therapy was studied. Patients receiving low-intensity warfarin therapy (targeted International Normalized Ratio [INR], 2-3) who had two consecutive baseline PTs within 10% of each other were recruited. Patients who regularly consumed grapefruit juice or alcohol or who were taking drugs known to interact with grapefruit juice were excluded. A one-week supply of freshly prepared frozen grapefruit juice in individual 8-oz containers was given to all the subjects, who were told to drink the entire contents of on container three times a day for one week. PTs were measured and INRs calculated on the day before grapefruit juice ingestion began (day 0) and a days 2, 6, and 8. Ten men (mean age, 66 years) were enrolled; one withdrew because of diarrhea. Compliance in consuming the juice was reported to range from 85.7% to 100% among patients. There was no significant difference among PT or INR values over the course of the study in any of the nine subjects. Ingestion of grapefruit juice prepared from frozen concentrate did not change PTs in patients treated with warfarin.

Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women.

This study determined relationships among total energy intake, nutrient intake, body composition, exercise group status, and annual rates of change (slopes) in bone mineral density in 66 Caucasian premenopausal women (mean age, 34.4 +/- 2.7) taking calcium supplements. Body composition components measured by dual-energy X-ray absorptiometry included fat mass, soft tissue lean mass, and bone mineral density (g/cm2) of total body, spine (lumbar vertebrae 2-4), and three femur sites measured at baseline, 5, 12, and 18 mo. Nutrients were not significant variables in regression models predicting bone mineral density slopes (rates of change) at any femur site. The only significant variable in models predicting Ward's triangle bone mineral density slope was the initial fat mass and, for trochanter, exercise. Significant variables (P < 0.05) in models predicting total body bone mineral density slope included the initial fat mass and fat mass slope plus either vitamin A, carotene, fiber, magnesium, or phosphorus (R2 from 0.31 to 0.25) and fat mass slope plus sodium (R2 = 0.24). The significant variable in the model predicting L2-4 slope was energy intake (R2 = 0.17, P < 0.05). We conclude that nutrient intake, exercise, and body composition are related to bone mineral density rate of change and that relations among these variables vary by bone site.

Prediction of body composition in premenopausal females from dual-energy X-ray absorptiometry.

Four methods for predicting body composition were compared in premenopausal females (n = 100), 28-39 yr old, by using underwater weighing (UWW) as the criterion method. The four methods were dual energy X-ray absorptiometry (DEXA), skinfolds, bioelectrical impedance, and body mass index. The sample had a mean percent fat (%fat) of 29.7 +/- 6.8% (SD) by DEXA and 29.9 +/- 5.8% measured by UWW. DEXA yielded a standard error of estimate (SE) of 2.4% (r = 0.91) for the prediction of %fat from UWW. When %fat was estimated from other methods, larger SEs were obtained: 3.0% for skin-folds, 3.3% for body mass index, and 2.9% for bioelectrical impedance (height2/resistance) plus weight. Individual body density values derived from UWW were corrected for bone mineral variation. DEXA predicted the corrected body density with a lower SE (0.0040 vs. 0.0053 g/ml) than the original density values. We conclude that DEXA was a precise method and correlated highly with fat-free body weight and %fat from UWW in this homogeneous female sample.

Relationship of body fat percentage and fat distribution with dehydroepiandrosterone sulfate in premenopausal females.

Dehydroepiandrosterone (DHEA) has an antiobesity effect in rodents, and elevated endogenous levels of its sulfate ester (DHEAS) are associated with reductions in risk for cardiovascular disease (CVD) in men. To examine the association of body fat and fat distribution, established correlates of CVD and CVD risk factors, with circulating DHEAS levels in women, we measured trunk and limb skinfold thicknesses and circumferences, total and regional body fat from dual energy x-ray absorptiometry (DXA), and serum levels of DHEAS in 96 healthy Caucasian females aged 28-39 yr. Body mass index, percentage fat from DXA and the waist-to-hip ratio were not significantly correlated (r < or = 0.15, P > or = 0.156) with serum DHEAS levels, regardless of statistical control for age, smoking behavior, and fasting status. However, the ratio of trunk/total skinfold thicknesses (r = 0.23, P = 0.030) and the percentage of total fat located on the trunk from DXA (r = 0.32, P = 0.002) were positively correlated with DHEAS, whereas the ratio of leg/total skinfold thicknesses (r = -0.25, P = 0.015) and the percentage of total fat located on the legs from DXA (r = -0.25, P = 0.015) were inversely correlated with DHEAS after adjusting for age, smoking, and fasting status. With the exception of the trunk/total skinfold thickness ratio, the correlations of DXA- and skinfold-derived estimates of fat distribution remained significant (P < or = 0.033) even after further adjustment for percentage fat or body mass index. It is concluded that increased amounts of total fat located on the trunk and decreased amounts of total fat located on the legs are associated with increased serum DHEAS concentrations in normally menstruating females.

Resistance exercise training is associated with decreases in serum low-density lipoprotein cholesterol levels in premenopausal women.

BACKGROUND: Aerobic exercise training is associated with reduced serum concentrations of triglycerides, increased concentrations of high-density lipoprotein cholesterol, and minimal changes in serum levels of total cholesterol or low-density lipoprotein cholesterol. There are few data on the effects of resistance exercise on blood lipid levels. METHODS: Premenopausal women were randomly assigned to a supervised resistance exercise training program (n = 46) or a control group (n = 42) for 5 months. Serum was analyzed for levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Body composition and dietary intake were also measured. RESULTS: The exercise group showed a 0.33 +/- 0.03-mmol/L (mean +/- SE) decrease in total cholesterol level and a 0.36 +/- 0.001-mmol/L decrease in low-density lipoprotein cholesterol level that was significantly different from the control group. No significant changes were noted in serum high-density lipoprotein cholesterol or triglyceride levels in either group. Changes in body composition showed no significant correlations with changes in total cholesterol or low-density lipoprotein cholesterol. There were no significant differences in nutrient intake between the groups. CONCLUSION: In healthy, premenopausal women, with normal baseline lipid profiles, 5 months of resistance exercise training was associated with significant decreases in serum total cholesterol and low-density lipoprotein cholesterol concentrations.

Bone mineral content of cyclically menstruating female resistance and endurance trained athletes.

The bone mineral content (BMC) at four sites on the axial and appendicular skeleton was compared among four groups of young adult (age = 17-38 yr) cyclically menstruating athletes (N = 40) who regularly performed either weightlifting resistance exercise (body builders) or nonresistance endurance exercise (runners, swimmers) and an inactive group of females (N = 18) of about equal age. Forearm BMC was measured using single photon absorptiometry at proximal (shaft) and distal sites on the radius. Dual photon absorptiometry was used to measure BMC at the lumbar vertebrae (L2-4) and femur at the femoral neck, Ward's triangle, and greater trochanter. Fat-free body mass (FFBM) was estimated from densitometry. Body builders had greater BMC than swimmers, collegiate runners, recreational runners, and controls. Mean differences in BMC among runners, swimmers, and controls were not significant (P less than or equal to 0.05). FFBM was correlated significantly with BMC (r = 0.35-0.56) at each site in the combined group of athletes (N = 39), whereas total body weight and BMC were correlated significantly at the distal radius site (r = 0.38) only. The results suggest that weight training may provide a better stimulus for increasing BMC than run and swim training.

Estimation of total body composition by regional dual photon absorptiometry.

The accuracy of estimating total body composition from dual photon absorptiometry (DPA) and the soft tissue attenuation ratio (Rst) from regional scans over the abdomen was investigated in a group (n = 82) of young adult (age = 17-38 years) females with diverse activity histories. Forearm bone mineral content (BMC) was estimated from single photon absorptiometry. Lumbar vertebrae and femur BMC, and trunk (lumbar region) soft tissue composition (Rst) were estimated from DPA. Percent body fat, the criterion variable, was estimated from body density (BD) after adjusting for individual variation in BMC, an important source of variability in body density. The test-retest reliability of Rst, assessed in a second group of subjects (n = 30), was excellent (r = 0.99; SEM = 0.10%). Rst was significantly (P ≤ .05) correlated with body density (r = .78), limb and especially trunk skinfolds, and predicted total body fat (%) with an SEE of 3.9%. These results demonstrate that DPA is a useful technique for obtaining estimates of both bone mineral and soft tissue composition, particularly in populations suspected to have significant bone loss. Given the association between Rst and trunk (abdominal) fat, DPA may prove to be a useful technique for investigating the association between abdominal fat and disease.

Effects of aerobic training on exercise tolerance and echocardiographic dimensions in untrained postmenopausal women.

The cardiovascular effects of physical training were evaluated in a controlled trial involving 32 healthy, untrained, postmenopausal women. The subjects were randomly assigned to an aerobic exercise training program or a control group. The exercise group participated in at least three 40-minute supervised sessions per week for 8 months. Twenty-five subjects completed the study: eight in the control group and 17 in the training group. The training group had a significant increase over the training period in maximal oxygen consumption (27.3 +/- 4.6 ml/kg/min vs 30.8 +/- 5.4 ml/kg/min, p less than 0.05) and maximal treadmill exercise duration (9.8 +/- 2.6 minutes vs 11.3 +/- 2.2 minutes; p less than 0.05). The control group had no significant change in maximal treadmill exercise duration (9.0 +/- 1.2 minutes vs 9.2 +/- 1.4 minutes) but had a slight increase in maximal oxygen consumption (23.7 +/- 3.4 ml/kg/min vs 24.4 +/- 4.1 ml/kg/min, p less than 0.05). The training group had significant increases in M-mode echocardiographic left ventricular end-diastolic dimension (4.6 +/- 0.6 cm vs 4.8 +/- 0.4 cm, p less than 0.05) and calculated left ventricular ejection fraction (0.66 +/- 0.14 vs 0.74 +/- 0.12, p less than 0.05). M-mode echocardiograms demonstrated no significant change in left ventricular dimensions or wall thickness in the control group. In this group of untrained postmenopausal women, a training effect was associated with enhanced resting left ventricular ejection fraction and increased resting left ventricular end-diastolic dimension.

One year of ethanol feeding increases circulating thyroid hormones in the dog.

Nine greyhound dogs were fed ethanol for 1 year to examine the effects of long-term ethanol feeding on circulating thyroid hormones. The dose of ethanol consumed per day was 2 gm/kg for the first month, 3 gm/kg for the second month, and 4 gm/kg for the rest of the study. Plasma triiodothyronine (T3), thyroxine (T4), and reverse triiodothyronine (rT3) were measured by radioimmunoassay. Plasma T3 and T4 concentrations increased significantly during the period of ethanol administration compared with control values (ANOVA, P less than 0.005). Levels of rT3 showed a trend to increase, although this was not significant. Resin T3 uptake decreased significantly (ANOVA, P less than 0.005) and the calculated free T4 index and free T3 index showed significant elevations (ANOVA, P less than 0.005) during ethanol administration. The results of this study indicate that long-term ethanol feeding to dogs induces an increase in circulating thyroid hormones.

Thyroidal changes associated with endurance training in women.

The associations between endurance training, body composition, and the pituitary-thyroid axis were studied in 17 healthy, young women. Body composition and plasma concentrations of T4, T3, rT3, resin T3 uptake, TSH, and TRH-stimulated TSH were examined at baseline and after each subject's weekly distance had increased 48 km (delta 48) and 80 km (delta 80) above baseline. Total body weight did not change at delta 48 or delta 80. Mean (+/- SE) lean weight in kg increased from 42.9 +/- 1.2 at baseline to 44.8 +/- 1.2 at delta 80 (P = 0.002). We have reported previously that at delta 48 the subjects had evidence of mild thyroidal impairment, which consisted of decreased T3 and rT3, and an exaggerated TSH response to TRH. With more prolonged training (delta 48 to delta 80) there were significant increases in T4, rT3, and unstimulated TSH, while the ratios of T4/rT3 and T3/rT3 and the TSH response to TRH decreased significantly. Some of the thyroidal changes that occurred between delta 48 and delta 80 are similar to those seen in other stressful non-thyroidal conditions.

Impaired gonadotropin responses to gonadotropin-releasing hormone stimulation in endurance-trained women.

The effects of endurance running on body composition, menstrual cycles, and gonadotropins were studied in 19 healthy, young, regularly menstruating women. Midfollicular plasma concentrations of unstimulated and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone and follicle-stimulating hormone were examined at baseline and after each subject's weekly mileage had increased 30 miles (delta 30) and 50 miles (delta 50) above baseline. Mean +/- standard error of the mean unstimulated luteinizing hormone and follicle-stimulating hormone did not change significantly. GnRH-stimulated luteinizing hormone was 76.3 +/- 22.0 micrograms/min/ml at baseline and declined to 20.2 +/- 4.5 micrograms/min/ml at delta 50 (P less than 0.02). GnRH-stimulated follicle-stimulating hormone was 28.4 +/- 7.0 micrograms/min/ml at baseline and declined to 9.6 +/- 2.1 micrograms/min/ml at delta 50 (P less than 0.02). There were no significant correlations between changes in body composition and changes in gonadotropin responses. Eighteen subjects developed oligomenorrhea.

Sex steroids and endurance running in women.

The effects of endurance training on body composition, menstrual cycles, and sex steroids were studied in 19 healthy, regularly menstruating women. Body composition and midfollicular plasma concentrations of estradiol (E2), estrone (E1), and testosterone (T) were examined at baseline and after each subject's weekly mileage had increased 30 miles (delta 30) and 50 miles (delta 50) above baseline. Total body weight did not change, but the subjects became leaner. Mean +/- standard error of the mean E2 decreased from 70.6 +/- 13.9 pg/ml at baseline to 33.6 +/- 4.8 pg/ml at delta 50 (P = 0.03). Mean E1 decreased progressively, but not significantly, while T did not change. Eighteen women developed menstrual changes (mainly oligomenorrhea), but not amenorrhea. Endurance running in women results in frequent menstrual dysfunction and is associated with a significant decrease in E2 concentrations.

Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients.

Chronic ethanol feeding impairs human chorionic gonadotropin-stimulated testicular testosterone responses of dogs.

To investigate the effects of ethanol on gonadal function, 24 male dogs were divided into four groups: the control group received no ethanol and the other three groups were fed varying amounts of ethanol for 30 days. Plasma concentrations of testosterone and luteinizing hormone (LH) were measured by radioimmunoassay after 30 days of ethanol or control feeding. At the conclusion of the experimental period the testes of each dog were examined for unstimulated and human chorionic gonadotropin (hCG)-stimulated testosterone production by means of an in vivo perfusion method. None of the dogs lost weight or had abnormal liver histology as a result of ethanol feeding. Control dogs and dogs fed ethanol (0.64 g/kg of body weight) showed no changes in gonadal function. Dogs fed ethanol (1.28 g/kg and 1.92 g/kg of body weight) had no decreases in peripheral concentrations of testosterone or LH, but hCG-stimulated testicular testosterone production was significantly impaired in both groups (P less than 0.005 and P less than 0.025, respectively). In addition, the dogs receiving ethanol at 1.92 g/kg of body weight had significantly (P less than 0.05) decreased unstimulated testicular testosterone production. It is concluded that a) daily ingestion of small amounts of ethanol does not cause obvious changes in gonadal function, b) peripheral concentrations of testosterone and LH may not accurately reflect early ethanol-induced gonadal dysfunction, c) hCG-stimulated testicular testosterone production is impaired when daily ethanol consumption is 1.28 g/kg of body weight or greater for 30 days, and d) these changes occur in the absence of weight loss or obvious liver pathology.

Prolactin responses, menstrual cycles, and body composition of women runners.

Fourteen young women with normal menses participated in an endurance running program to investigate the effects of physical training on menstrual function, plasma PRL, and body composition. Body composition, measured by hydrostatic weighing, and PRL (basal and TRH-stimulated ) were determined initially and after each subject had increased her weekly mileage by 30 miles (delta 30) and 50 miles (delta 50). Mean (+/- SEM) total body weight did not change, but the subjects became significantly leaner (relative fat, 25.5 +/- 1.3% at baseline vs. 22.4 +/- 0.9% at delta 50; P less than 0.02). Thirteen women developed menstrual changes (mainly oligomenorrhea), but not amenorrhea. Mean (+/- SEM) unstimulated PRL levels were 16.8 +/- 3.1%, 16.9 +/- 2.4, and 11.5 +/- 2.1 ng/ml at baseline, delta 30, and delta 50, respectively (P less than 0.03 at delta 50 compared to baseline and delta 30). Mean ( +/- SEM) integrated TRH-stimulated PRL responses increased from 5002 +/- 462 ng/ml.min at baseline to 5748 +/- 609 mg/ml.min at delta 30 and 6535 +/- 552 ng/ml.min at delta 50, and were significantly different from one another (F = 4.01; P less than 0.04). Endurance training, without total body weight loss or extreme leanness, results in frequent menstrual dysfunction. Other authors have shown that young female athletes have an increased PRL response to acute exercise compared to nonathletes. One mechanism responsible for menstrual dysfunction in endurance-trained women may be frequent and exaggerated PRL responses to exercise and other stimuli.

Evidence for mild thyroidal impairment in women undergoing endurance training.

The effects of endurance training on body composition and the pituitary-thyroid axis were studied in 29 healthy, young (mean age, 28.7 yr), regularly menstruating women. Women who were initially jogging a mean of 13.5 miles/week were selected for this study to minimize dropouts. Body composition, measured by hydrostatic weighing, and nonfasting plasma concentrations of T4, T3, rT3, TSH, and TRH-stimulated TSH, measured by RIA, were examined initially and after each subject's weekly mileage had increased to 30 miles ( delta 30) for at least 2 consecutive weeks. Two subjects were found to have compensated primary hypothyroidism and were not included in the subsequent data analysis. At delta 30, mean body weight did not change, mean fat weight decreased (- 1.02 kg; P less than 0.005), and mean lean weight increased (+0.75 kg; P less than 0.05). T4 and unstimulated TSH did not change. However, mean (+/-SE) T3 decreased from 107.2 +/- 4.4 to 97.9 +/- 3.4 ng/dl (P less than 0.025), and mean rT3 decreased from 170.9 +/- 13.9 to 154.6 +/- 13.2 pg/ml (P less than 0.025). The decreases in T3 and rT3 were accompanied by significantly greater TSH responses to TRH stimulation [mean (+/-SE) area under TSH curve, 1381.4 +/- 123 vs. 1712.8 +/- 202 micron IU/ml.min; P less than 0.01]. These results indicate that physically active women who undergo additional endurance training 1) become more lean without a change in total weight, and 2) have changes in T3, rT3, and TRH-stimulated TSH indicative of mild thyroidal impairment.

High density lipoprotein cholesterol and body composition of female runners.

Twenty-two women participating in an endurance running program had determinations of body composition, of plasma total cholesterol (TC) and HDL cholesterol (HDLC) concentrations before and after increasing their running by 30 miles/wk. Mean total body weight, fat weight and relative body fat showed significant decreases, while mean lean weight significantly increased. Mean HDLC increased 5 mg/dl (p less than 0.01). Although increases of HDLC correlated with increases in lean weight, exercise per se appears to increase HDLC of women.