Vol 71, No 6 (2021)
Review paper
Published online: 2021-10-29
The effect of physical activity on sex hormone levels in women. Implications for breast cancer risk
1
Nowotwory. Journal of Oncology 2021;71(6):383-390.
Abstract
Breast cancer is the most commonly diagnosed neoplastic disease in women, which leads to a significant deterioration in the quality of life and a reduction in the ability of women to function normally in everyday life. The main risk factor for breast cancer in both premenopausal and postmenopausal women is exposure to high levels of endogenous estrogen. It takes many years for neoplasia to develop, but lowering estrogen levels has been observed to reduce the risk of both a new diagnosis and recurrence of breast cancer. Observational studies have found that exercise reduces the level of bioavailable sex hormones, and thus may reduce the risk of developing breast cancer. Currently available evidence clearly shows that adequate levels of physical activity are associated with a 25–30% reduction in the average risk of breast cancer in women and play a role in its treatment.
This review summarizes the data available in the literature on the effect of physical activity on the level of sex hormones in women, while presenting the biological mechanisms underlying the relationship between physical activity and the development of breast cancer. This issue requires further research, but already now, extensive educational campaigns are needed which can be aimed at young women to inform them on the possibility of significantly reducing their risk of breast cancer by introducing physical activity into their everyday lives.
Keywords: exercisegonadal steroid hormonesestrogenrisk factorsbreast cancer
References
- Friedenreich CM. The role of physical activity in breast cancer etiology. Semin Oncol. 2010; 37(3): 297–302.
- Lee IM, Shiroma EJ, Lobelo F, et al. Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012; 380(9838): 219–229.
- Rock CL, Thomson C, Gansler T, et al. American Cancer Society guideline for diet and physical activity for cancer prevention. CA Cancer J Clin. 2020; 70(4): 245–271.
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–249.
- Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021 [Epub ahead of print].
- Lauby-Secretan B, Scoccianti C, Loomis D, et al. International Agency for Research on Cancer Handbook Working Group. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016; 375(8): 794–798.
- Key J, Hodgson S, Omar RZ, et al. Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes Control. 2006; 17(6): 759–770.
- Godinho-Mota JC, Gonçalves LV, Mota JF, et al. Sedentary Behavior and Alcohol Consumption Increase Breast Cancer Risk Regardless of Menopausal Status: A Case-Control Study. Nutrients. 2019; 11(8).
- Eliassen AH, Missmer SA, Tworoger SS, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 2006; 98(19): 1406–1415.
- Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev. 1993; 15(1): 36–47.
- Armstrong K, Eisen A, Weber B. Assessing the risk of breast cancer. N Engl J Med. 2000; 342(8): 564–571.
- Pike MC, Krailo MD, Henderson BE, et al. 'Hormonal' risk factors, 'breast tissue age' and the age-incidence of breast cancer. Nature. 1983; 303(5920): 767–770.
- Kamińska M, Ciszewski T, Łopacka-Szatan K, et al. Breast cancer risk factors. Prz Menopauzalny. 2015; 14(3): 196–202.
- McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000; 321(7261): 624–628.
- Russo J, Russo IH. Toward a physiological approach to breast cancer prevention. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1994; 3(4): 353–364.
- Lange CA, Yee D. Progesterone and breast cancer. Womens Health (Lond). 2008; 4(2): 151–162.
- Ismail PM, Amato P, Soyal SM, et al. Progesterone involvement in breast development and tumorigenesis--as revealed by progesterone receptor "knockout" and "knockin" mouse models. Steroids. 2003; 68(10-13): 779–787.
- Micheli A, Muti P, Secreto G, et al. Endogenous sex hormones and subsequent breast cancer in premenopausal women. Int J Cancer. 2004; 112(2): 312–318.
- Kossman DA, Williams NI, Domchek SM, et al. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer. J Appl Physiol (1985). 2011; 111(6): 1687–1693.
- Green J, Reeves GK, Floud S, et al. Million Women Study Collaborators, Million Women Study Collaborators, Million Women Study Collaborators, Million Women Study Collaboration, Million Women Study Collaborators, Million Women Study Collaborators, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003; 362(9382): 419–427.
- Kaaks R, Berrino F, Key T, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2005; 97(10): 755–765.
- Knochenhauer ES, Boots LR, Potter HD, et al. Differential binding of estradiol and testosterone to SHBG. Relation to circulating estradiol levels. J Reprod Med. 1998; 43(8): 665–670.
- Fortunati N, Catalano MG. Sex hormone-binding globulin (SHBG) and estradiol cross-talk in breast cancer cells. Horm Metab Res. 2006; 38(4): 236–240.
- Lynch BM, Neilson HK, Friedenreich CM. Physical activity and breast cancer prevention. Recent Results Cancer Res. 2011; 186: 13–42.
- McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008; 8(3): 205–211.
- Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000; 92(18): 1472–1489.
- Jasienska G, Ziomkiewicz A, Thune I, et al. Habitual physical activity and estradiol levels in women of reproductive age. Eur J Cancer Prev. 2006; 15(5): 439–445.
- Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr. 2002; 132(11 Suppl): 3456S–3464S.
- Samavat H, Kurzer MS. Estrogen metabolism and breast cancer. Cancer Lett. 2015; 356(2 Pt A): 231–243.
- Kabuto M, Akiba S, Stevens RG, et al. A prospective study of estradiol and breast cancer in Japanese women. Cancer Epidemiol Biomarkers Prev. 2000; 9(6): 575–579.
- Key TJ, Appleby PN, Reeves GK, et al. Endogenous Hormones and Breast Cancer Collaborative Group. Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol. 2013; 14(10): 1009–1019.
- De Souza MJ, Miller BE, Loucks AB, et al. High frequency of luteal phase deficiency and anovulation in recreational women runners: blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. J Clin Endocrinol Metab. 1998; 83(12): 4220–4232.
- Thune I, Brenn T, Lund E, et al. Physical activity and the risk of breast cancer. N Engl J Med. 1997; 336(18): 1269–1275.
- El-Lithy A, El-Mazny A, Sabbour A, et al. Effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women. J Obstet Gynaecol. 2015; 35(4): 389–392.
- Verloop J, Rookus MA, van der Kooy K, et al. Physical activity and breast cancer risk in women aged 20-54 years. J Natl Cancer Inst. 2000; 92(2): 128–135.
- Bullen BA, Skrinar GS, Beitins IZ, et al. Induction of menstrual disorders by strenuous exercise in untrained women. N Engl J Med. 1985; 312(21): 1349–1353.
- Williams NI, Reed JL, Leidy HJ, et al. Estrogen and progesterone exposure is reduced in response to energy deficiency in women aged 25-40 years. Hum Reprod. 2010; 25(9): 2328–2339.
- Smith AJ, Phipps WR, Arikawa AY, et al. Effects of aerobic exercise on premenopausal sex hormone levels: results of the WISER study, a randomized clinical trial in healthy, sedentary, eumenorrheic women. Cancer Epidemiol Biomarkers Prev. 2011; 20(6): 1098–1106.
- Jasienska G, Ellison PT. Energetic factors and seasonal changes in ovarian function in women from rural Poland. Am J Hum Biol. 2004; 16(5): 563–580.
- Jasieńska G, Ellison PT. Physical work causes suppression of ovarian function in women. Proc Biol Sci. 1998; 265(1408): 1847–1851.
- Ennour-Idrissi K, Maunsell E, Diorio C. Effect of physical activity on sex hormones in women: a systematic review and meta-analysis of randomized controlled trials. Breast Cancer Res. 2015; 17(1): 139.
- Williams NI, Leidy HJ, Hill BR, et al. Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction. Am J Physiol Endocrinol Metab. 2015; 308(1): E29–E39.
- Lieberman JL, DE Souza MJ, Wagstaff DA, et al. Menstrual Disruption with Exercise Is Not Linked to an Energy Availability Threshold. Med Sci Sports Exerc. 2018; 50(3): 551–561.
- Kabat GC, Chang CJ, Sparano JA, et al. Urinary estrogen metabolites and breast cancer: a case-control study. Cancer Epidemiol Biomarkers Prev. 1997; 6(7): 505–509.
- Campbell KL, Westerlind KC, Harber VJ, et al. Associations between aerobic fitness and estrogen metabolites in premenopausal women. Med Sci Sports Exerc. 2005; 37(4): 585–592.
- Bentz AT, Schneider CM, Westerlind KC. The relationship between physical activity and 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2/16 ratio in premenopausal women (United States). Cancer Causes Control. 2005; 16(4): 455–461.
- Pasagian-Macaulay A, Meilahn EN, Bradlow HL, et al. Urinary markers of estrogen metabolism 2- and 16 alpha-hydroxylation in premenopausal women. Steroids. 1996; 61(8): 461–467.
- Campbell KL, Westerlind KC, Harber VJ, et al. Effects of aerobic exercise training on estrogen metabolism in premenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2007; 16(4): 731–739.
- Speroff L, Glass RH. Clinical Gynecologic Endocrinology and Infertility 6th ed. Lippincott Williams & Wilkins 1999.
- Powell L. Too much of a good thing: female athlete triad. Mo Med. 2011; 108(3): 176–178.
- Horn E, Gergen N, McGarry KA. The female athlete triad. R I Med J (2013). 2014; 97(11): 18–21.
- De Souza MJ, Hontscharuk R, Olmsted M, et al. Physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism in exercising women. Hum Reprod Update. 2004; 10(5): 433–448.
- Morris FL, Wark JD. An effective, economic way of monitoring menstrual cycle hormones in at risk female athletes. Med Sci Sports Exerc. 2001; 33(1): 9–14.
- Morris FL, Payne WR, Wark JD. Prospective decrease in progesterone concentrations in female lightweight rowers during the competition season compared with the off season: a controlled study examining weight loss and intensive exercise. Br J Sports Med. 1999; 33(6): 417–422.
- Cho GJ, Han SW, Shin JH, et al. Effects of intensive training on menstrual function and certain serum hormones and peptides related to the female reproductive system. Medicine (Baltimore). 2017; 96(21): e6876.
- Diet, nutrition, physical activity and breast cancer. American Institute for Cancer Research 2018. http://www.wcrf.org/sites/default/files/Prostate-Cancer-2014-Report.pdf%0Ahttp://www.aicr.org/continuous-update-project/reports/breast-cancer-report-2017.pdf%0Adietandcancerreport.org.
- Borch KB, Braaten T, Lund E, et al. Physical activity before and after breast cancer diagnosis and survival - the Norwegian women and cancer cohort study. BMC Cancer. 2015; 15: 967.
- Irwin ML, Smith AW, McTiernan A, et al. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008; 26(24): 3958–3964.
- Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol. 2002; 20(4): 1128–1143.
- Lahart IM, Metsios GS, Nevill AM, et al. Physical activity, risk of death and recurrence in breast cancer survivors: A systematic review and meta-analysis of epidemiological studies. Acta Oncol. 2015; 54(5): 635–654.
- Biganzoli E, Desmedt C, Demicheli R. Does Physical Activity Have an Impact on Recurrence Dynamics in Early Breast Cancer Patients? J Clin Med. 2021; 10(4).
- Savolainen-Peltonen H, Vihma V, Leidenius M, et al. Breast Adipose Tissue Estrogen Metabolism in Postmenopausal Women With or Without Breast Cancer. J Clin Endocrinol Metab. 2014; 99(12): E2661–E2667.
- Stone SA, Han CJ, Senn T, et al. Sex Hormones in Women With Elevated Breast Cancer Risk Undergoing Weight Loss. West J Nurs Res. 2019; 41(11): 1602–1622.
- Kossman DA, Williams NI, Domchek SM, et al. Exercise lowers estrogen and progesterone levels in premenopausal women at high risk of breast cancer. J Appl Physiol (1985). 2011; 111(6): 1687–1693.
- Jasienska G, Ziomkiewicz A, Thune I, et al. Habitual physical activity and estradiol levels in women of reproductive age. Eur J Cancer Prev. 2006; 15(5): 439–445.
- Howard RA, Leitzmann MF, Linet MS, et al. Physical activity and breast cancer risk among pre- and postmenopausal women in the U.S. Radiologic Technologists cohort. Cancer Causes Control. 2009; 20(3): 323–333.
- Ghosn B, Benisi-Kohansal S, Ebrahimpour-Koujan S, et al. Association between healthy lifestyle score and breast cancer. Nutr J. 2020; 19(1): 4.
- Furberg AS, Jasienska G, Bjurstam N, et al. Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study. Cancer Epidemiol Biomarkers Prev. 2005; 14(1): 33–40.
- Kapiszewska M, Miskiewicz M, Ellison PT, et al. High tea consumption diminishes salivary 17beta-estradiol concentration in Polish women. Br J Nutr. 2006; 95(5): 989–995.
- Rosendahl AH, Perks CM, Zeng Li, et al. Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer. Clin Cancer Res. 2015; 21(8): 1877–1887.
- Kiyama R. Estrogenic Activity of Coffee Constituents. Nutrients. 2019; 11(6).
- Finstad SE, Emaus A, Potischman N, et al. Influence of birth weight and adult body composition on 17beta-estradiol levels in young women. Cancer Causes Control. 2009; 20(2): 233–242.
- Kloss JD, Perlis ML, Zamzow JA, et al. Sleep, sleep disturbance, and fertility in women. Sleep Med Rev. 2015; 22: 78–87.
- Merklinger-Gruchala A, Ellison PT, Lipson SF, et al. Low estradiol levels in women of reproductive age having low sleep variation. Eur J Cancer Prev. 2008; 17(5): 467–472.
- Sowers MF, Zheng H, Kravitz HM, et al. Sex steroid hormone profiles are related to sleep measures from polysomnography and the Pittsburgh Sleep Quality Index. Sleep. 2008; 31(10): 1339–1349.
- Healy GN, Matthews CE, Dunstan DW, et al. Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003-06. Eur Heart J. 2011; 32(5): 590–597.
- Lynch BM. Sedentary behavior and cancer: a systematic review of the literature and proposed biological mechanisms. Cancer Epidemiol Biomarkers Prev. 2010; 19(11): 2691–2709.
- Ravi S, Kujala UM, Tammelin TH, et al. Adolescent Sport Participation and Age at Menarche in Relation to Midlife Body Composition, Bone Mineral Density, Fitness, and Physical Activity. J Clin Med. 2020; 9(12).
- Calthorpe L, Brage S, Ong KK. Systematic review and meta-analysis of the association between childhood physical activity and age at menarche. Acta Paediatr. 2019; 108(6): 1008–1015.
- Al-Azzawi F, Palacios S. Hormonal changes during menopause. Maturitas. 2009; 63(2): 135–137.
- Bertone-Johnson ER, Tworoger SS, Hankinson SE. Recreational physical activity and steroid hormone levels in postmenopausal women. Am J Epidemiol. 2009; 170(9): 1095–1104.
- Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996; 81(4): 1495–1501.
- Robles Gil MC, Timón R, Toribio AF, et al. Effects of aerobic exercise on urinary estrogens and progestagens in pre and postmenopausal women. Eur J Appl Physiol. 2012; 112(1): 357–364.
- Key TJ, Appleby PN, Reeves GK, et al. Endogenous Hormones and Breast Cancer Collaborative Group. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer. 2011; 105(5): 709–722.
- Dallal CM, Brinton LA, Matthews CE, et al. Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism. Med Sci Sports Exerc. 2016; 48(3): 439–448.
- Dallal CM, Tice JA, Buist DSM, et al. B~FIT Research Group. Estrogen metabolism and breast cancer risk among postmenopausal women: a case-cohort study within B~FIT. Carcinogenesis. 2014; 35(2): 346–355.
- Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998; 19(1): 1–27.
- Neilson HK, Friedenreich CM, Brockton NT, et al. Physical activity and postmenopausal breast cancer: proposed biologic mechanisms and areas for future research. Cancer Epidemiol Biomarkers Prev. 2009; 18(1): 11–27.
- van Kruijsdijk RCM, van der Wall E, Visseren FLJ. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009; 18(10): 2569–2578.
- CAULEY J, GUTAI J, KULLER L, et al. THE EPIDEMIOLOGY OF SERUM SEX HORMONES IN POSTMENOPAUSAL WOMEN. American Journal of Epidemiology. 1989; 129(6): 1120–1131.
- Lukanova A, Lundin E, Zeleniuch-Jacquotte A, et al. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Eur J Endocrinol. 2004; 150(2): 161–171.
- Enger SM, Ross RK, Paganini-Hill A, et al. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol Biomarkers Prev. 2000; 9(7): 681–687.
- Key TJ, Appleby PN, Reeves GK, et al. Endogenous Hormones Breast Cancer Collaborative Group. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 2003; 95(16): 1218–1226.
- Renehan A, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008; 371(9612): 569–578.
- Aune D, Rosenblatt DAN, Chan D, et al. Anthropometric factors and endometrial cancer risk: a systematic review and dose–response meta-analysis of prospective studies. Annals of Oncology. 2015; 26(8): 1635–1648.
- Oh H, Coburn SB, Matthews CE, et al. Anthropometric measures and serum estrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study. Breast Cancer Res. 2017; 19(1): 28.
- Berry TR, Jones KE, Courneya KS, et al. Believability of messages about preventing breast cancer and heart disease through physical activity. BMC Psychol. 2018; 6(1): 2.