Richard D. Bulbrook

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.

The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom)

The association with breast cancer of menstrual and reproductive events, family history of breast cancer, and body size have been studied on two cohorts of 6,706 volunteers on the island of Guernsey (United Kingdom), 168 of whom had breast cancer detected during follow-up. The median follow-up time of the non-cases was 21 years in the first study and 10 years in the second. A time-dependent Cox regression model was fitted to the data with age as the time-dependent variable in order to represent the effect of changing menopausal status. Other variables examined in the model were age at menarche, parity, age at first birth, family history of breast cancer, height, weight (both directly measured), relative weight (weight [kg]/height[m]), and Quetelets body mass index (weight[kg]/height[m]2). Interactions between age and all other covariates also were examined. Family history was found to be the most important risk factor for women aged less than 51 years (relative risk [RR]=3.5, 95 percent confidence interval [CI]=2.0–6.0), and intervals between menarche and first birth longer than 14 years were found to increase significantly the risk of breast cancer in women older than 61 years (RR=2.4, CI=1.3–4.4). Height was the only indicator of body size which was associated significantly with risk of breast cancer, the estimated regression coefficient indicating an increase in risk of about 70 percent for women on the 90th centile of height relative to those on the 10th centile. A survey of the literature showed that the association between risk of breast cancer and height was found in those studies which used direct measurements of height but not in others which used self-reported values.

Serum progesterone concentration during the luteal phase in women with benign breast disease.

Earlier studies of the serum concentration of progesterone during the luteal phase in women with benign breast disease have produced conflicting results. Serum progesterone profiles were therefore measured in relation to cyclical breast pain and in biopsied benign disease. No evidence of progesterone deficiency was found.

Selenium in human mammary carcinogenesis: a case-cohort study

In a prospective study conducted on the island of Guernsey a cohort of 5162 ostensibly healthy women was enrolled between 1967 and 1976. Blood samples were drawn from each participant, who also completed a questionnaire, which provided information on established risk indicators in human mammary carcinogenesis. Plasma selenium levels were measured in 46 breast cancer cases diagnosed a mean of 11 (S.D. 4) years after entry into the study cohort and in an age-stratified sample of 138 women drawn from the study base. Plasma selenium level in the cases was 109 (28) micrograms/l and in the base sample 103 (22) micrograms/l (95% confidence interval for the overall difference, -2 to 14 micrograms/l). The adjusted relative risk of developing breast cancer in the different quartiles of the selenium distribution was 0.80, 0.79, 0.72 and 1.00, respectively. Thus, in the present study selenium was not a strong indicator of human breast cancer risk.

A comparison of mammographic parenchymal patterns in premenopausal Japanese and British women

Normal premenopausal Japanese women have significantly more favourable mammographic parenchymal patterns (Wolfe Grades) than comparable British women. This finding is unaffected when the women are stratified by age, Quetelets Index, age at menarche, age at first birth, and parity.

Urinary androgen metabolites and recurrence rates in early breast cancer.

Androsterone and aetiocholanolone were measured in urine specimens obtained from 218 women with early breast cancer. Patients who excreted less than the median amount of these steroids had a significantly higher recurrence rate (P less than 0.005) than patients excreting more than the median value. The relationship between androgen excretion and recurrence is stronger in pre-menopausal women that in the post-menopausal group. The androgen assays are still associated with recurrence rates when patients are stratified by pathological stage, but no clear relationship was found with histological grade.

Serum oestradiol-17β and prolactin concentrations during the luteal phase in women with benign breast disease

Serum profiles of both oestradiol and prolactin were measured during the luteal phase in normal women, in women with cyclical breast pain and in women with recently biopsied benign breast disease. The results suggest that, in women with benign breast disease, the concentration of both hormones may be increased, when compared to the normal controls, during the evening in the latter part of the luteal phase.

A comparison of epidemiological characteristics in breast cancer patients and normal women in Great Britain and Japan: results of a prospective study.

SummaryThe epidemiological characteristics of normal women and women with early breast cancer in Great Britain were prospectively compared with similar subjects from Japan. The study consisted of 204 women with early breast cancer and 792 normal controls from Great Britain and 200 breast cancers and 335 Japanese controls. The risk factors examined were age, height and weight, menopausal status, age at menarche and menopause, parity, age at first birth, use of oral contraceptives, and family history of breast cancer. The cancers and cases were divided into pre- and postmenopausal groups. There was a striking trend for a protective effect of multiparity in both countries and a weak but inconstant protective effect of age at first birth. In premenopausal British women increase in body mass was significantly associated with a decreased risk of breast cancer but this association was not found for postmenopausal women or in the Japanese women. The results showed that the classical risk factors did not fully account for the differences in breast cancer risk between Great Britain and Japan. The possibility that aetiological factors might be changing warrants investigation.

Urinary androgen and 17-hydroxylated corticosteroid metabolites and their relation to recurrence rates in early breast cancer

SummaryThe amounts of urinary androsterone and etiocholanolone are highly correlated with recurrence rates in patients with early breast cancer after treatment by mastectomy. A more efficient means of predicting the clinical course of the disease is obtained by using a ratio of these compounds to the amounts of individual 17-hydroxycorticosteroids in the urine. For instance, the ratio of androsterone to a-cortolone is particularly effective in identifying women with a high rate of recurrence, and this is largely independent of pathological stage and tumor grade.