title: Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors.
abstract: Mammographic density is strongly associated with breast cancer risk, and endogenous hormones, which are risk factors for breast cancer, may be involved in the mechanism. This cross-sectional study of 494 premenopausal women is the first to account for cyclic variations in estrogen levels, by measuring urinary estrone glucuronide (E1G) in the periovulatory and luteal phases of the menstrual cycle, and to assess the role of androgens. Computer-assisted density readings were obtained from digitized mammograms. Mean ovulatory E1G level and daily E1G load were both positively associated with percent density before adjustment for body mass index (BMI), with women in the top fourth having 10.2% (95% CI: 2.9%, 18.1%) and 8.9% (1.7%, 16.7%), respectively, higher density than those in the bottom fourth (Ptrend before/after BMI adjustment=0.006/0.11 and 0.01/0.13, respectively). Neither the peak nor luteal E1G levels were predictive of density after adjustment for E1G levels at other points in the cycle. The plasma androgens testosterone, androstenedione, and dehydroepiandrosterone sulfate were negatively associated with density. In mutually adjusted analyses, density was positively associated with insulin-like growth factor (IGF)-I and negatively with IGF-II (Ptrend=0.006 for both) but not with IGF binding protein-3. There was also weak evidence of a positive association of prolactin with density. The study supports the hypothesis that endogenous hormones affect density in premenopausal women; in particular, it shows a positive association between estrogen levels and density and suggests that the mean level throughout the cycle is the most biologically relevant measure. Most of these hormone-density associations were attenuated with further adjustment for BMI.
authors.affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, and The Academic Department of Biochemistry, The Royal Marsden Hospital, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Walker
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
authors.forename: Nichola
authors.initials: N
authors.lastname: Johnson
authors.forename: Ben
authors.initials: B
authors.lastname: Coupland
authors.forename: Valerie A
authors.initials: VA
authors.lastname: McCormack
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Folkerd
authors.forename: Lorna
authors.initials: L
authors.lastname: Gibson
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Hillier
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Holly
authors.forename: Sue
authors.initials: S
authors.lastname: Moss
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Isabel
authors.initials: I
authors.lastname: dos Santos Silva
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002138:Calibration; D003430:Cross-Sectional Studies; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D042361:Mammary Glands, Human / Q000033:anatomy & histology; D008327:Mammography / Q000592:standards; D008597:Menstrual Cycle / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D017697:Premenopause / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D011388:Prolactin / Q000097:blood*; D013002:Somatomedins / Q000032:analysis* / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; D013002:Somatomedins; D011388:Prolactin