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Objectives: To describe the patterns and to assess the indicators of hormone use during the menopausal transition period in a Dutch population., Methods: Between 1993 and 1997, 17,357 women aged 49-70 years participated in the Prospect-EPIC (European Prospective Investigation into Cancer and Nutrition) cohort and filled out an extensive questionnaire, which included information about hormone use during menopausal transition and other medical and lifestyle characteristics. Patterns of hormone use were described and various characteristics were evaluated as indicators of current hormone use by logistic regression., Results: Overall, 13% of women were current hormone users, which was highest in the 49-54 age group (19%). Hysterectomized women and older non-hysterectomized women mainly used unopposed estrogen therapy (ET), whereas younger non-hysterectomized women mainly used oral contraceptives or combined estrogen+progestogen therapy. Of all ever users, 61% used hormones for more than 1 year and 28% for more than 5 years. The most important indicators of hormone use for women without a surgical menopause were age, alcohol use, smoking, parity, ever use of oral contraceptives and family history of breast cancer. For women with a surgical menopause age, parity, ever use of oral contraceptives, diastolic blood pressure and the number of removed ovaries were the most relevant indicators., Conclusions: The frequency of hormone use during menopausal transition in the Netherlands is low compared to other western countries, but the duration of use is quite long. Hormone use seems to be largely determined by factors that are known to affect endogenous estrogen levels.

The presence of the PvuII or the XbaI polymorphism in the estrogen receptor alpha gene (ESR1, 6q25) has been related to breast cancer risk; however, results are not fully consistent. To further elucidate this relation, we examined these polymorphisms in relation with mammographic density, a measure of dense tissue in the breast, which is strongly associated with breast cancer risk. For this study, 620 participants aged 49 to 68 years were selected from the Prospect-European Prospective Investigation into Cancer and Nutrition cohort. Blood samples, lifestyle- and medical questionnaire data and mammograms were available for these women. Genotyping was done using the TaqMan PCR assay and mammographic density was assessed using a computer-assisted method. Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for Pp and pp are 37% and 36%, respectively) than in those with the PP genotype (32%, P(trend) = 0.09). Women with one or two copies of the XbaI x allele had higher mean percentage density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype (31%, P(trend) < 0.01). Haplotype 1 (px) was associated with increased density, whereas haplotype 2 (PX) was associated with decreased density, both suggesting an allele-dose effect (P(trend) = 0.08 and <0.01, respectively). Similar associations were found with absolute density (P(trend) < 0.01). The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated., Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women., Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.