Abstract
Objective: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer.
Methods: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance.
Results: SHBG decreased with increasing body mass index and increasing waist–hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women.
Conclusions: Certain factors such as obesity and perhaps waist–hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.
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Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15: 17-035.
Key TJ, Verkasalo PK (1999) Endogenous hormones and the aetiology of breast cancer. Breast Cancer Research:http:/breast-cancer-research.com/vol1no1/23aug99/editorial/2.
Henderson BE, Pike MC, Bernstein L, Ross RK (1996) Breast cancer. In: Schottenfeld D, Fraumeni JFJ, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, pp. 1022-1039.
Longnecker MP (1994) Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes Control 5: 73-82.
Sonnenschein E, Toniolo P, Terry MB, et al. (1999) Body fat distribution and obesity in pre-and postmenopausal breast cancer. Int J Epidemiol 28: 1026-1031.
Riboli E, Kaaks R (1997) The EPIC project: rationale and study design. Int J Epidemiol 26(Suppl. 1): 6-14.
Thomas HV, Davey GK, Key TJ (1999) Estradiol and sex-hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans. Br J Cancer 80: 1470-1475.
Dowsett M, Goss PE, Powles TJ, et al. (1987) Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res 47: 1957-1961.
Muti P, Trevisan M, Micheli A, et al. (1998) Alcohol consumption and total estradiol in premenopausal women. Cancer Epidemiol Biomarkers Prev 7: 189-193.
Key TJ (1999) Serum estradiol and breast cancer risk. Endocrine-Related Cancer 6: 175-180.
Muti P, Trevisan M, Micheli A, et al. (1996) Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period. Cancer Epidemiol Biomarkers Prev 5: 917-922.
Michaud DS, Manson JE, Spiegelman D, et al. (1999) Reproductibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period. Cancer Epidemiol Biomarkers Prev 8: 1059-1064.
Siiteri PK, MacDonald PC (1973) Role of extraglandular estrogen in human endocrinology. In: Greep RO, Astwood EB, eds. Handbook of Physiology. Washington, DC: American Physiological Society, pp. 615-629.
Judd HL, Shamonki IM, Frumar AM, Lagasse LD (1982) Origin of serum estradiol in postmenopausal women. Obstet Gynecol 59: 680-686.
Lapidus L, Lindstedt G, Lundberg P-A (1986) Concentrations of sex-hormone binding globulin and corticosteroid binding globulin in serum in relation to cardiovascular risk factors and to12-year incidence of cardiovascular disease and overall mortality in postmenopausal women. Clin Chem 32: 146-152.
Ernster VL, Wrensch MR, Petrakis NL, et al. (1987) Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens. J Natl Cancer Inst 79: 949-960.
Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG (1989) The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol 129: 1120-1131.
Kaye SA, Folsom AR, Soler JT, Prineas RJ, Potter JD (1991) Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol 20: 151-156.
Ingram DM, Nottage EM, Willcox DL, Roberts A (1990) Oestrogen binding and risk factors for cancer. Br J Cancer 61: 303-307.
Dorgan JF, Reichman ME, Judd JT, et al. (1995) The relation of body size to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States). Cancer Causes Control 6: 3-8.
Hankinson SE, Willett WC, Manson JE, et al. (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst 87: 1297-1302.
Newcomb PA, Klein R, Klein BEK, et al. (1995) Association of dietary and life-style factors with sex hormones in postmenopausal women. Epidemiology 6: 318-321.
Nagata C, Kabuto M, Takatsuka N, Shimizu H (1997) Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women. Breast Cancer Res Treat 44: 235-241.
Madigan MP, Troisi R, Potischman N, Dorgan JF, Brinton LA, Hoover RN (1998) Serum hormone levels in relation to reproduc-tive and lifestyle factors in postmenopausal women (United States). Cancer Causes Control 9: 199-207.
Hunter DJ, Willett WC (1993) Diet, body size, and breast cancer. Epidemiol Rev 15: 110-132.
Potischman N, Swanson CA, Siiteri P, Hoover RN (1996) Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 88: 756-758.
Thomas HV, Key TJ, Allen DS, et al. (1997) Re: Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 89: 396-397.
Nagata C, Kaneda N, Kabuto M, Shimizu H (1997) Factors associated with serum levels of estradiol and sex hormone-binding globulin among premenopausal Japanese women. Environ Health Perspect 105: 994-997.
Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N (1990) Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab. 70: 473-479.
Haffner SM, Katz MS, Dunn JF (1991) Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women. Int J Obes 15: 417-478.
Schapira DV, Kumar NB, Lyman GH (1991) Obesity, body fat distribution, and sex hormones in breast cancer patients. Cancer 67: 2215-2218.
Pasquali R, Vicennati V, Bertazzo D, et al. (1997) Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Metabolism 46: 5-9.
Huang Z, Willett WC, Colditz GA, et al. (1999) Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses' Health Study. Am J Epidemiol 150: 1316-1324.
Arena B, Maffulli N, Maffulli F, Morleo MA (1995) Reproductive hormones and menstrual changes with exercise in female athletes. Sports Med 19: 278-287.
Bernstein L, Ross RK, Lobo RA, Hanisch R, Krailo MD, Henderson BE (1987) The effects of moderate physical activity on mensrual cycle patterns in adolescence: implications for breast cancer prevention. Br J Cancer 55: 681-685.
Nelson ME, Meredith CN, Dawson-Hughes B, et al. (1988) Hormone and bone mineral status in endurance trained and sedentary postmenopausal women. J Clin Endocrinol Metab 66: 927-933.
Ginsburg ES (1999) Estrogen, alcohol and breast cancer risk. J Steroid Biochem Mol Biol 69: 299-306.
Reichman ME, Judd JT, Longcope C, et al. (1993) Effects of alcohol consumption on plasma and urinary hormone concen-trations in premenopausal women. J Natl Cancer Inst 85: 722-727.
Dorgan JF, Reichman ME, Judd JT, et al. (1994) The relation of reported alcohol ingestion to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States). Cancer Causes Control 5: 53-60.
Martin CA, Mainous AG 3rd, Curry T, Martin D (1999) Alcohol use in adolescent females: correlates with estradiol and testoster-one. Am J Addict 8: 9-14.
Gavaler JS, Deal SR, Van Thiel DH, Arria A, Allan MJ (1993) Alcohol and estrogen levels in postmenopausal women: the spectrum of effect. Alcohol Clin Exp Res 17: 786-790.
Ginsburg ES, Mello NK, Mendelson JH, et al. (1996) Effects of alcohol ingestion on estrogens in postmenopausal women. JAMA 276: 1747-1751.
Michnovicz JJ, Herschcopf RJ, Naganuma H, Bradlow HL, Fishman J (1986) Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking. N Engl J Med 315: 1305-1309.
MacMahon B, Trichopoulos D, Cole P, Brown J (1982) Cigarette smoking and urinary estrogens. N Engl J Med 307: 1062-1065.
Khaw K-T, Chir MBB, Tazuke S, Barrett-Connor E (1988) Cigarette smoking and levels of adrenal androgens in postmeno-pausal women. N Engl J Med 318: 1075-1079.
Law MR, Cheng R, Hackshaw AK, Allaway S, Hale AK (1997) Cigarette smoking, sex hormones and bone density in women. Eur J Epidemiol 13: 553-558.
Hankinson SE, Colditz GA, Hunter DJ, et al. (1995) Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses' Health Study (United States). Cancer Causes Control 6: 217-224.
Apter D, Reinilä M, Vihko R (1989) Some endocrine character-istics of early menarche, a risk factor for breast cancer, are preserved into adulthood. Int J Cancer 44: 783-787.
Moore JW, Key TJA, Wang DY, Bulbrook RD, Hayward JL, Takatani O (1991) Blood concentrations of estradiol and sex hormone-binding globulin in relation to age at menarche in premenopausal British and Japanese women. Breast Cancer Res Treat 18: S47-S50.
Bernstein L, Pike MC, Ross RK, Henderson BE (1991) Age at menarche and estrogen concentrations of adult women. Cancer Causes Control 2: 221-225.
Musey VC, Collins DC, Brogan DR, et al. (1987) Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens. J Clin Endocrinol Metab 64: 111-118.
Petrakis NL, Wrensch MT, Ernster VL, et al. (1987) Influence of pregnancy and lactation on serum and breast fluid estrogen levels: implications for breast cancer risk. Int J Cancer 40: 587-591.
Dorgan JF, Reichman ME, Judd JT, et al. (1995) Relationships of age and reproductive characteristics with plasma estrogens and androgens in premenopausal women. Cancer Epidemiol Biomarkers Prev 4: 381-386.
Moore JW, Key TJA, Bulbrook RD, et al. (1987) Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones. Br J Cancer 56: 661-666.
Bernstein L, Pike MC, Ross RK, Judd HL, Brown JB, Henderson BE (1985) Estrogen and sex hormone-binding globulin levels in nulliparous and parous women. J Natl Cancer Inst 74: 741-745.
Yu MC, Gerkins VR, Henderson BE, Brown JB, Pike MC (1981) Elevated levels of prolactin in nulliparous women. Br J Cancer 43: 826-831.
Russo J, Tay LK, Russo IH (1982) Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res Treat 2: 5-73.
Key TJA, Pike MC, Moore JW, et al. (1989) The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy. Contraception 39: 179-186.
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Verkasalo, P.K., Thomas, H.V., Appleby, P.N. et al. Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom). Cancer Causes Control 12, 47–59 (2001). https://doi.org/10.1023/A:1008929714862
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DOI: https://doi.org/10.1023/A:1008929714862