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Biomedical subjects

R D Bulbrook

Publications and source records attributed to R D Bulbrook.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1990

Relationship of mammographic parenchymal patterns with breast cancer risk factors and risk of breast cancer in a prospective study.

A prospective study has been conducted on 4954 female volunteers from the Island of Guernsey between 1977 and 1985 to examine risk factors for breast cancer and their relationship to mammographic parenchymal patterns as assessed by Wolfe's method of grading. Up to September 1988, 69 women had developed breast cancer, 11 of whom were prevalent cases being diagnosed within six months of mammography. The remaining incident cases were diagnosed six to 126 months (median 65 months) after entry to the study. Univariate analysis showed that the distribution of Wolfe grades in the population was significantly associated with menopausal status, age, parity, adiposity, age at menarche, age at first childbirth and use of oral contraception, but not with a family history of breast cancer. Multivariate analysis of the data for these variables from either pre- and/or post-menopausal women indicated that age, parity and adiposity were significantly related to Wolfe grade pattern. Age had an opposite effect in pre- compared with postmenopausal women thus the probability of either a P2 or DY pattern increased with increasing age in premenopausal but decreased in postmenopausal women so that incidence peaked around the menopause. Other variables did not achieve significance in the multivariate analysis. Odds ratios (ORs) were calculated for women with P2 or DY patterns using those with N1 or P1 grades as the reference group. The ORs were determined at two censoring times; one at five years and the other to include the most recent follow-up of this cohort. The ORs were adjusted for years of follow-up, age and adiposity and in postmenopausal women adjustment was also made for age at menarche.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

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↗
PubMed1989

Hormones are ambiguous risk factors for breast cancer.

Women with breast cancer whose blood and urinary androgens are at the lower end of the normal range have an early age at diagnosis, a rapid recurrence rate after mastectomy and tumours that are unresponsive to endocrine therapy. The most plausible explanation for these results is that the androgens are not involved in tumour initiation but control tumour growth rates after the malignant transformation has occurred. If this is so, endocrine case/control studies in which growth rates are not measured are an inefficient way of studying the endocrinology of breast cancer. It is suggested that the oestrogens and androgens should be considered as a single functional unit in future research.

Adult↗
PubMed1988

Effects of prednisolone on sex hormone binding globulin during primary endocrine treatment of advanced breast cancer.

Serum sex hormone binding globulin (SHBG) was measured in 21 pre and 39 postmenopausal women with advanced breast cancer before treatment and 1, 3, 6, 9 and 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice daily, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. Ovarian irradiation was associated with a 25% reduction in serum SHBG levels 3 to 6 months after treatment whilst patients on tamoxifen experienced a rise of about 80% in serum SHBG levels after 1 to 3 months. In postmenopausal women prednisolone markedly dampened the effect of tamoxifen, reducing a 80% rise to about 20%. There was no relationship between SHBG levels and response to treatment.

Breast Neoplasms↗
PubMed1988

The distribution of estradiol in the sera of normal Caucasian, Chinese, Filipina, Hawaiian and Japanese women living in Hawaii.

Mean concentrations of sex-hormone-binding-globulin (SHBG) and the percentage distribution of estradiol between the non-protein-bound, albumin-bound and SHBG-bound fractions were not different in Caucasian, Hawaiian, Chinese, Japanese and Filipinas living in Hawaii. The widely varying incidence rates for breast cancer are therefore not explained by variations in the availability of estradiol.

Adult↗
PubMed1988

The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women.

In each of two population-based studies conducted on the Island of Guernsey between 1967-1976 and 1977-1984, respectively, single specimens of blood were taken from over 5000 normal women. From these two studies there were 1173 and 946 postmenopausal women in whom blood prolactin was determined and multivariate analysis was used to establish the association between blood prolactin concentration and possible determinants of risk of breast cancer. Since prolactin levels were log-normally distributed these analyses were done on log-transformed data. The age at menarche or menopause, age at first or last childbirth, length of reproductive life (i.e. time from menarche to menopause) or post-menopausal life (i.e. time from menopause to time of blood sampling), contraceptive use and history of breast cancer were not significantly associated with blood prolactin concentration. Of significance were age, parity, time of blood sampling and assay drift. Ponderosity (Quetelet's Index) was positively associated with prolactin concentration and this was significant using a one-tail criterion. Women with a mammographic pattern designated DY by Wolfe had significantly higher prolactin levels than those with N1 patterns. However, the main finding to emerge was that after standardizing for all the other variables increasing parity was related to a step-wise reduction in blood prolactin levels. Since this had occurred in women who had had their last child up to 35 years previously it implies this effect is permanent. It could therefore be that the protective effect on breast cancer risk of multiparity and early first pregnancy could be mediated by such a life-long reduction in blood prolactin levels.

Age Factors↗
PubMed1988

Urinary epidermal growth factor excretion and breast cancer risk.

The amount of urinary epidermal growth factor (EGF) excreted was determined in 350 normal women of whom 37 subsequently developed breast cancer. These were a group of women selected on a case-control basis from 5000 volunteers who had participated in a prospective epidemiological study. Urinary EGF excretion was not correlated with known risk factors such as age at menarche or menopause, age at first or last full-term child or parity. Neither was it associated with day or length of menstrual cycle, breast mammographic parenchymal pattern or the blood concentration of prolactin, dehydroepiandrosterone or its sulphate ester. Univariate analysis indicated that the amount of urinary EGF was significantly correlated with urinary creatinine (P less than 0.001), age (P less than 0.001), urinary androsterone (P less than 0.02) or aetiocholanolone (P less than 0.02), height (P less than 0.05) and weight (P less than 0.05). However, multivariate analysis showed that the amount of urinary EGF was correlated only with creatinine excretion (P less than 0.001) and age (P less than 0.001) and that the significance of the other correlations were probably due to the confounding influence of creatinine.

Adult↗
PubMed1988

A prospective study of the relationship between serum vitamins A and E and risk of breast cancer.

In an 8 year prospective study (1977-1985) on breast cancer, blood was taken from 5,086 women resident in Guernsey, and the serum stored at -20 degrees C. During this period 30 women developed the disease and their serum samples were analysed for vitamins A and E, and for retinol-binding protein (RBP). A further 288 age-matched control sera (up to 10 per pre-cancer case) were similarly analysed. No relationship was found between any of these substances and subsequent development of breast cancer. A significant correlation between increasing age and vitamin A (r = 0.46, P less than 0.001) and RBP (r = 0.36, P less than 0.001) concentrations was observed. There was also a trend for increased blood concentrations of vitamin E with age, but this was not significant. Serum RBP and vitamin A concentrations were highly correlated (r = 0.91, P less than 0.0001).

Adult↗
PubMed1988

Sex hormone-binding globulin and the natural history of breast cancer.

Low concentrations of SHBG in the blood appear to be related to rapid tumour growth rates whereas normal values are associated with slower rates. The inferences drawn from these and other experimental results are as follows: 1. It is no longer necessary to postulate that an abnormal endocrine environment is related to the risk of breast cancer. 2. Variation within the normal range of endocrine function may be sufficient to account for marked differences in the growth rates of transformed cells. 3. It is suggested that women whose tumours arise in an environment characterised by SHBG concentrations at the lower end of the normal range (and, hence, non-SHBG-bound oestradiol levels at the top end of the range) will tend to have an earlier age at diagnosis, a lower frequency of oestrogen-receptor positive tumours and a lower proportion of hormone responsive tumours than women with SHBG levels at the top of the range. 4. Case/control studies in which growth rates are not taken into account may be difficult to interpret.

Adult↗
PubMed1987

The relationship between blood prolactin levels and risk of breast cancer in premenopausal women.

Single specimens of blood have been taken from over 5000 normal volunteer women in each of two sequential (1967-1976, 1977-1984) population-based studied on the Island of Guernsey. Multivariate analysis was used to determine the relationship between prolactin levels and risk factors in breast cancer in 2591 and 1959 premenopausal women in whom blood prolactin had been measured. In both populations the prolactin concentrations appeared to be log-normally distributed and therefore all analyses have been done on log-transformed data. Initially the variables in the statistical model were age at menarche, ages at first and last baby, parity, ponderosity (Quetelet Index), mammographic pattern (as graded by Wolfe), family history of breast cancer, age, menstrual cycle status, time of day of blood sampling, oral contraceptive use, history of breast feeding and methodological changes in the laboratory measurement of prolactin. Of these variables age at menarche, ages at first and last child and family history of breast cancer were found not to be significant and were excluded from the final model. The main finding to emerge was that after standardizing for all the other variables, prolactin levels in the follicular phase were significantly lower than those found at midcycle or during the luteal phase of the menstrual cycle. A peak level of prolactin was found at day 12 of the cycle. Increasing parity was related to a steady decrease in prolactin concentration. Increasing ponderosity was associated with an increased prolactin level as was a DY compared to an N1 mammographic pattern. Women with a history of oral contraceptive use had lowered prolactin concentration. All these effects occurred evenly over the menstrual cycle and were generally found for both data sets. Thus body weight, parity and, indirectly, age at first baby might influence breast cancer risk by being associated with changes in blood prolactin concentration.

Adult↗
PubMed1987

Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones.

Sex hormone binding globulin (SHBG) concentrations were measured by immunoradiometric assay in serum samples from 1,221 healthy female volunteers aged 34-79 who had never used oral contraceptives or hormone replacement therapy, had no history of thyroid disease or cancer, and had not used any drugs known to influence SHBG in the 14 days preceding blood sampling. There were 616 premenopausal and 605 naturally postmenopausal women. In both premenopausal and postmenopausal women, SHBG decreased with increasing weight (Quetelt's Index) and was lower in single nulliparous women than in married nulliparous women or parous women. In premenopausal women, SHBG was higher in women with late menarche, was higher in smokers than in non-smokers, and was higher in blood samples taken during the first 12 days of the luteal phase than during the rest of the menstrual cycle. In postmenopausal women, SHBG increased with years since the menopause. The possible biological importance of these findings is discussed with particular reference to risk factors for breast cancer.

Adult↗
PubMed1987

Foetal steroid binding protein in British and Japanese women.

In order to examine the newly-discovered sex-steroid binding protein, foetal steroid binding protein (FSBP) in different populations, its binding characteristics and its level were studied by two-tier column ligand binding assay and enzyme-linked immunosorbent assay (ELISA) respectively. In 10 Japanese premenopausal women, analysis of 5 alpha-dihydrotestosterone (DHT) binding in the Cibacron Blue 3GA-Sepharose 6B portion of the column showed a rising plateau pattern with a mean maximum binding of 31.1 +/- 7.41%, whereas of 9 similar British women, 8 displayed unsaturable, non-cooperative binding of 11.6 +/- 8.22% (P less than 0.01). After partial purification of FSBP in these samples, the protein exhibited saturable binding kinetics, median binding 25 (interquartiles 23-34) and 19 (13-25) nmol DHT/l in Japanese and British women, respectively (P less than 0.05). By analyzing FSBP by ELISA in 56 Japanese (45 premenopausal) and 59 British (25 premenopausal) women, higher levels were obtained in the whole Japanese group (P = 0.0016) and in the premenopausal Japanese women (P = 0.018) than in their British counterparts. In both nationalities, FSBP levels were higher in premenopausal women, and there was a significant negative correlation of FSBP with age in both populations, particularly in postmenopausal women. FSBP levels did not correlate with weight, parity, sex hormone binding globulin or albumin levels. The influence of FSBP on free steroid levels remains unclear, but some relationship with ovarian function seems a possibility.

Adult↗
PubMed1987

Adjuvant androgen treatment of operable breast cancer--a 20 year analysis.

One hundred and fifty-five patients with carcinoma of the breast treated by mastectomy were randomised to receive no additional treatment or to receive adjuvant testosterone. After a minimum follow up of 15 years there is no difference in either relapse free survival or overall survival between the treated and control groups. Stratification by pathological nodal status showed no benefit either for those with negative or positive axillary lymph node involvement.

Adult↗
PubMed1986

Binding of oestradiol to blood proteins and aetiology of breast cancer.

A prospective study of 5,000 women has shown that, compared to controls, those who subsequently developed breast cancer had a higher proportion of their blood oestradiol in the non-protein-bound and albumin-bound fractions (the bio-available fraction) and a lower proportion in the sex-hormone-bound fraction. The increased proportion of bio-available oestradiol was partly due to a lower concentration of sex-hormone-binding globulin. Weight was excluded as a confounding factor.

Adult↗