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T J Key

Publications and source records attributed to T J Key.

At least 73 records · Page 4Linked to original sources

Validation of weighed records and other methods of dietary assessment using the 24 h urine nitrogen technique and other biological markers.

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion:dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1.13. Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r -0.62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0.74 and 0.82, and between dietary vitamin C and beta-carotene and plasma vitamin C and beta-carotene 0.86 and 0.48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0.78-0.87). Those between N from estimated food records and urine N were r 0.60-0.70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0.01 to 0.5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy.

Basal Metabolism↗

Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records.

Women (n 160) aged 50 to 65 years were asked to weigh their food for 4 d on four occasions over the period of 1 year, using the PETRA (Portable Electronic Tape Recorded Automatic) scales. Throughout the year, they were asked to complete seven other dietary assessment methods: a simple 24 h recall, a structured 24 h recall with portion size assessments using photographs, two food-frequency questionnaires, a 7 d estimated record or open-ended food diary, a structured food-frequency (menu) record, and a structured food-frequency (menu) record with portion sizes assessed using photographs. Comparisons between the average of the 16 d weighed records and the first presentation of each method indicated that food-frequency questionnaires were not appreciably better at placing individuals in the distribution of habitual diet than 24 h recalls, due partly to inaccuracies in the estimation of frequency of food consumption. With a 7 d estimated record or open-ended food diary, however, individual values of nutrients were most closely associated with those obtained from 16 d weighed records, and there were no significant differences in average food or nutrient intakes.

Diet Records↗

A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women.

The aim of the study was to examine the relationships of obesity, lipids and apolipoproteins with the risk for subsequent ischaemic heart disease in middle-aged women, using a case-control study nested within a cohort study. A total of 3634 women aged 26-88 were recruited in Guernsey between 1977 and 1985 and followed until June 1986 by abstraction of their general practitioners' records. Fifty-one cases of incident ischaemic heart disease (11 myocardial infarction, 40 angina) were identified. For each case up to 4 controls were selected, matched for age and date at recruitment. Odds ratios for the development of ischaemic heart disease in the middle and upper thirds of the distribution for each variable in the controls, relative to the lowest third (and two-sided P-values for linear trends), were: 3.0, 2.6 (0.015) for Quetelet's index; 3.3, 5.1 (0.003) for total cholesterol; 0.5, 0.6 (0.102) for apolipoprotein A-I; 1.8, 2.4 (0.015) for apolipoprotein B; 1.3, 2.1 (0.155) for apolipoprotein(a). The increased risks associated with increased Quetelet's index and total cholesterol were independent of each other and these variables were more strongly related to myocardial infarction than to angina. The relationships of risk with serum cotinine, fatty acids, dehydroepiandrosterone sulphate and sex hormone binding globulin were weak and did not approach statistical significance.

Adult↗

Sex hormones and cancer.

There are few instances in which a clear effect of hormones on cancer risk is known and in which the effects of those hormones on the cells concerned are also known. The best examples are the relationships between sex hormones and cancer in women. The effects of sex hormones both on the risk for endometrial cancer and on the cells of the endometrium are well understood, and the evidence strongly suggests that hormones act by altering the rate of cell division. The same mechanism may explain the relationships between sex hormones and the risk for breast cancer, but our understanding of cancers at this site is incomplete. Less still is known about the mechanisms of the effects of sex hormones on other hormone-related cancers, such as those of the ovary and cervix. Most sex hormones are not genotoxic.

Carcinogens↗

Serum hormone levels in British and rural Chinese females.

The comparison of blood levels of oestradiol, testosterone, prolactin, and sex-hormone binding globulin (SHBG) was made of 3250 rural Chinese and 300 British women, aged 35 to 64. To reduce the number of assays performed the blood samples were combined so as to form 390 and 30 pools, respectively. The Chinese had significantly less oestradiol and testosterone. Prolactin levels were similar in both races. SHBG was significantly lower in postmenopausal British women. In the Chinese women, testosterone was positively and prolactin negatively correlated with breast cancer mortality.

Adult↗

Blood concentrations of estradiol and sex hormone-binding globulin in relation to age at menarche in premenopausal British and Japanese women.

In a cross-sectional study, serum estradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were not significantly related to age at menarche in premenopausal British women in the luteal or follicular phases of the cycle. In Japanese subjects in the luteal phase, a marginally higher concentration of E2 was observed in those who had undergone an early rather than a late menarche. In British women, previous oral contraceptive users had significantly lower luteal phase E2 concentrations than never users.

Adult↗

Cigarette smoking and steroid hormones in women.

Epidemiological evidence has suggested that cigarette smoking has an anti-oestrogenic effect in women, but the effects of smoking on steroid hormone metabolism are not fully understood. We compared serum concentrations of oestradiol, progesterone (luteal phase) and dehydroepiandrosterone sulphate (DHEA-S), and urinary excretion rates of six steroids of predominantly adrenal origin, in healthy premenopausal and postmenopausal female smokers and non-smokers. Serum concentrations of oestradiol, progesterone and DHEA-S did not differ between smokers and non-smokers by greater than 5%, and none of these differences was statistically significant. Mean urinary excretion rates of androsterone, aetiocholanolone, DHEA, 11-keto-aetiocholanolone, 11-hydroxyandrosterone and 11-hydroxyaetiocholanolone were very similar in smokers and non-smokers in premenopausal women, but were from 2-44% higher in smokers than non-smokers in postmenopausal women. The difference was statistically significant only for 11-hydroxyandrosterone. These results confirm previous reports that cigarette smoking does not affect serum oestradiol in premenopausal or postmenopausal women, but provide only weak evidence to support previous findings of increased levels of some adrenal steroids in postmenopausal women smokers. The mechanism for the apparent anti-oestrogenic effect of cigarette smoking remains unclear.

Adult↗

A case-control study of dietary carotene in men with lung cancer and in men with other epithelial cancers.

Dietary carotene intake during the year before diagnosis was estimated for 96 men with lung cancer, 75 men with other epithelial cancers, and 97 hospital controls. Relative to those of men in the lowest third of carotene intake (less than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the middle (1,683-2,698 micrograms/day) and upper (greater than 2,698 micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65, respectively, for other epithelial cancers (one-sided test for trend p = 0.074). The protective effect of estimated dietary carotene intake was considerably stronger than was the effect of total intake of carotene-rich vegetables and fruits (grams per day), providing some evidence that the protective factor is carotene itself rather than another component of vegetables and fruits.

Aged↗

The relationship of free fatty acids with the binding of oestradiol to SHBG and to albumin in women.

Free fatty acid concentration, sex hormone binding globulin (SHBG) concentration, % free oestradiol and % SHBG-bound oestradiol were measured in fasting and non-fasting serum samples from 48 women. Free fatty acids were 128% higher (P less than 0.001) and % SHBG-bound oestradiol was 11% lower (P = 0.001) in fasting than non-fasting samples, but these changes were not significantly correlated (r = -0.16, P = 0.287). Mean SHBG concentration and % free oestradiol did not differ significantly between fasting and non-fasting samples. Between subject correlations were calculated for measurements from 30 premenopausal women: % free oestradiol was inversely correlated with SHBG and free fatty acids and positively correlated with Quetelet's Index; % SHBG-bound oestradiol was positively correlated with SHBG but was not consistently or significantly related to free fatty acids or Quetelet's Index. It was concluded that physiological increases in free fatty acid concentrations do not increase % free oestradiol and that free fatty acids are less important than SHBG concentration and perhaps other variables in determining differences between individuals in oestradiol binding to SHBG.

Adult↗

Sex hormones in women in rural China and in Britain.

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.

Adult↗

Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

Adult↗

Long term effects of a first pregnancy on serum concentrations of dehydroepiandrosterone sulfate and dehydroepiandrosterone.

A previous paper in this journal reported that first pregnancy was followed by a marked decrease in dehydro-epiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA) levels. We report here confirmatory observations from cross-sectional measurements in 460 women. In premenopausal subjects (n = 306), the mean DHAS level was 21% lower (P = 0.005) and the mean DHA level was 32% lower (P less than 0.001) in parous than in nulliparous women. Neither DHAS nor DHA was related to parity in postmenopausal women (n = 154).

Adult↗

The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy.

Sex hormone binding globulin (SHBG) concentration was measured in serum samples from 2077 premenopausal and 901 naturally postmenopausal women who had no history of disease or of recent drug use likely to affect SHBG. Current users of oral contraceptives (OCs) and of oestrogen replacement therapy had higher mean SHBG values than non-current users. Both premenopausal and postmenopausal women who had previously used OCs had a lower mean SHBG concentration than never users of OCs. Previous use of oestrogen replacement therapy was not related to SHBG.

Adult↗

LHRH agonists and the prevention of breast and ovarian cancer.

Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.

Breast Neoplasms↗

The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer.

The protective effect of early menopause shows that ovarian hormones increase the risk of breast cancer: it is likely that this is because they stimulate breast cell division. The mitotic rate of breast cells is higher during the luteal phase of the menstrual cycle than during the follicular phase, suggesting either that progesterone and oestrogen together induce more mitoses than oestrogen alone (the 'oestrogen plus progestagen hypothesis') or that oestrogen alone induces breast cell mitoses in a dose-dependent manner and that progesterone has no effect (the 'oestrogen alone hypothesis'). Both hypotheses are consistent with the known effects of reproductive history, obesity, combined oral contraceptives and oestrogen replacement therapy (ERT) on breast cancer risk, but while the oestrogen alone hypothesis predicts that hormone replacement therapy with oestrogen and a progestagen (HRT) will cause the same increase in risk as ERT, the oestrogen plus progestagen hypothesis predicts that HRT will cause a greater increase in risk than ERT. Both hypotheses suggest that the risk of breast cancer could be reduced by delaying the onset of regular ovulatory menstrual cycles and by minimizing the therapeutic use of oestrogens, and possibly of progestagens, in postmenopausal women. It may be possible to design hormonal contraceptives that will decrease breast cancer risk.

Adult↗

The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk.

The 'unopposed oestrogen hypothesis' for endometrial cancer maintains that risk is increased by exposure to endogenous or exogenous oestrogen that is not opposed simultaneously by a progestagen, and that this increased risk is due to the induced mitotic activity of the endometrial cells. Investigation of the mitotic rate during the menstrual cycle shows that increases in plasma oestrogen concentration above the relatively low levels of the early follicular phase do not produce any further increase in the mitotic rate of endometrial cells. A modification of the unopposed oestrogen hypothesis which includes this upper limit in the response of endometrial cells to oestrogen is consistent with the known dose-effect relationships between endometrial cancer risk and both oestrogen replacement therapy and postmenopausal obesity; it also suggests that the mechanism by which obesity increases risk in premenopausal women involves progesterone deficiency rather than oestrogen excess, and that the protective effect of cigarette smoking may be greater in postmenopausal than in premenopausal women. Detailed analysis of the age-incidence curve for endometrial cancer in the light of this hypothesis suggests that there will be lifelong effects of even short duration use of exogenous hormones. In particular, 5 years of combination-type oral contraceptive use is likely to reduce a woman's lifetime risk of endometrial cancer by some 60%; whereas 5 years of unopposed oestrogen replacement therapy is likely to increase her subsequent lifetime risk by at least 90%; and even 5 years of 'adequately' opposed therapy is likely to increase subsequent lifetime risk by at least 50%.

Adult↗