A prospective study of urinary oestrogen excretion and breast cancer risk

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125

113

Summary The associations between serum concentrations of oestradiol, progesterone, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in premenopausal women were investigated in a prospective study of breast cancer on the island of Guernsey. Sixty-two women diagnosed with breast cancer an average of 8 years subsequent to blood collection were matched for day of menstrual cycle, age and year of blood collection with 182 control subjects. Cases had a 12% higher mean oestradiol concentration over the whole menstrual cycle (P = 0.17) with a large difference at mid-cycle (75% higher, P = 0.04). Differences between cases and control subjects in progesterone (luteal phase), testosterone and SHBG were small and not statistically significant: luteal phase progesterone 9% lower in cases, P = 0.64; testosterone 4% higher, P = 0.57; SHBG 8% higher, P = 0.24. The small difference in oestradiol concentration could be aetiologically important, but larger prospective studies are needed.

Section: Discussionmentioning

confidence: 56%

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confidence: 99%

A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey

Thomas¹,

Key²,

Allen³

et al. 1997

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125

113

“…To assess whether there was evidence for deterioration of the samples with long-term storage, we examined the association of total oestrogen excretion (oestrone + oestradiol + oestriol) with the year of urine collection in these samples plus other samples from the same cohort, which were collected later and were assayed for analysis in a nested case-control study of oestrogen excretion and breast cancer risk (Key et al, 1996) …”

Section: Subjectsmentioning

confidence: 99%

Cigarette smoking and urinary oestrogen excretion in premenopausal and post-menopausal women

Key¹,

Pike²,

Brown³

et al. 1996

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Summary Cigarette smoking is associated with a reduction in the risk for endometrial cancer in postmenopausal women and it has been suggested that this is because smoking has an anti-oestrogenic effect. To investigate this, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167 premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women (54 smokers, 146 non-smokers). Among premenopausal women there were no significant differences in oestrogen excretion between smokers and non-smokers. Among post-menopausal women, geometric mean excretion rates for oestrone and oestradiol did not differ significantly between groups, but oestriol excretion was 19% lower (95% confidence interval -34% to -1 %) in smokers than in non-smokers. This may partly explain the reduced risk for endometrial cancer among post-menopausal smokers.Keywords: cigarette smoking; urinary oestrogen; endometrial cancer risk; epidemiologyIn comparison with non-smokers, women who smoke have a lower risk of post-menopausal endometrial cancer, an earlier menopause and a higher incidence of osteoporosis, and it has been suggested that all these associations are consequences of an anti-oestrogenic effect of cigarette smoking (Baron, 1984). The protective effect against post-menopausal endometrial cancer is substantial; for example, in a large population-based case-control study, Brinton et al. (1993) reported a relative risk of 0.4 in current smokers vs never smokers. Although this finding is of no direct value in preventing endometrial cancer, understanding of the mechanism involved is important and a number of studies have therefore investigated the association of cigarette smoking with sex hormones.MacMahon et al. (1982) reported that premenopausal women smokers have reduced urinary excretion of oestrone, oestradiol and oestriol in the luteal phase (but not in the follicular phase) of the menstrual cycle and suggested that this might be caused by reduced oestrogen production. Subsequent investigations have shown that the relationship of cigarette smoking with steroid hormones is complex. Several studies have reported that smoking increases adrenal activity, resulting in increased serum concentrations of androstenedione and dehydroepiandrosterone sulphate, and of progesterone in post-menopausal women (and in the early follicular phase) (Friedman et al., 1987;Schlemmer et al., 1990;Zumoff et al., 1990;Cassidenti et al., 1992). Smoking is not associated with serum concentrations of endogenous oestradiol among premenopausal or post-menopausal women (Friedman et al., 1987;Khaw et al., 1988;Longcope and Johnston, 1988;Cauley et al., 1989;Zumoff et al., 1990;Key et al., 1991;Berta et al., 1992;Cassidenti et al., 1992;Daniel et al., 1992). These results suggest that the protective effect of smoking might be due to the increase in androgens and/or progesterone rather than due to a reduction in oestrogen exposure, although other investigations suggest that smoking does alter the metabolism of oestradio...

“…We have specifically tested the hypotheses that serum oestradiol and testosterone concentrations are positively associated with breast cancer risk, while serum SHBG concentration is negatively associated with risk. Results for urinary oestrogen excretion for 31 of these cases, which showed a significantly higher mean excretion rate for the sum of oestrone, oestradiol and oestriol in the cases than in the controls, have recently been published (Key et al, 1996).…”

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confidence: 99%

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

Thomas¹,

Key²,

Allen³

et al. 1997

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202

(SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, Pfor trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.