Women in Steady Exercise Research [Formerly Women, Oxidative Stress, Exercise and Estrogens (WOSEE)] (WISER)

RATIONALE: Exercising regularly may lower the risk of breast cancer. PURPOSE: This randomized clinical trial is studying how well exercise prevents breast cancer in healthy young women.

OBJECTIVES: Primary Compare the changes in urine levels of a stable marker of oxidative stress (F_2-isoprostanes) in healthy young women who undergo exercise training during 4 menstrual cycles vs no exercise. Secondary Assess the changes in other metabolic factors that explain the association between physical activity and breast cancer, including: Estrogen metabolism (estrone, estradiol, estriol, 2-OHE_1, 2-OHE_2, 2-MeOHE_1, 2-MeOHE_2, 4-OHE_1, 4-OHE_2 [as well as ratios of these metabolites], insulin-like growth factor (IGF)-1 (as well as IGF-binding proteins-1, -2, and -3, insulin, glucose, body composition (including body mass index, lean mass, and body fat [DEXA scan]). OUTLINE: This is a randomized, controlled study. Participants are stratified according to baseline body fat percentage and age (18 to 24 years vs 25 to 30 years). Participants are randomized to 1 of 2 intervention arms. Arm I: Participants exercise for 30 minutes 5 times a week. The intensity of exercise is increased every 4 weeks. The exercise regimen continues for up to 4 menstrual cycles. Arm II: Participants are observed for 4 menstrual cycles. Participants in both arms undergo 24-hour collection of urine on days 7, 8, and 9 of menstrual cycles 1 and 6. F_2-isoprostanes are measured via gas chromatography-mass spectrometry (GC/MS). Estrogens are also measured by GC/MS and include E_1, E_2, E_3, 2-OHE_1, 2-OHE_2, 4-OHE_1, 4-OHE_2, 2-MeE_1, 2-MeE_2, 4-MeE_1, 4-MeE_2, and 16OHE_1. Participants undergo blood collection, body mass measurement by dual-energy x-ray absorptiometry, and a fitness assessment twice during the 6-month study. PROJECTED ACCRUAL: A total of 400 participants will be accrued.

Inclusion Criteria: Healthy women Self-reported menstrual cycle length of 25-35 days within the past 2 months Nonsmoker Sedentary (exercise < 3 times weekly within the past 6 months) Intact ovaries and uterus No history of gynecological problems (e.g., fibroids, endometriosis, polycystic ovary syndrome) Female Premenopausal Body mass index 18.5 to 40 Stable weight (no changes ≥ 10% within the past year) Exclusion Criteria: No pregnancy or breast feeding within the past 6 months No plans to become pregnant during study treatment No cancer within the past 5 years except for nonmelanoma skin cancers No medical condition that would prohibit participation in a vigorous program of weight-bearing aerobic exercise including, but not limited to, any of the following: Fibromyalgia Chronic fatigue syndrome Metabolic disorders Recent cardiovascular event Orthopedic limitations Psychiatric disorders requiring antipsychotic drugs No uncontrolled hypertension (systolic blood pressure [BP] > 160 mm Hg and/or diastolic BP > 99 mm Hg) No more than 7 alcoholic beverages per week No injected hormonal contraceptive use within the past year More than 6 months since prior use of intrauterine device More than 3 months since prior oral or patch hormone contraceptives No medication that would prohibit participation in a vigorous program of weight-bearing aerobic exercise

Crawford TN, Arikawa AY, Kurzer MS, Schmitz KH, Phipps WR. Cross-sectional study of factors influencing sex hormone-binding globulin concentrations in normally cycling premenopausal women. Fertil Steril. 2015 Dec;104(6):1544-51. doi: 10.1016/j.fertnstert.2015.08.040. Epub 2015 Sep 16.

Arikawa AY, Jakits HE, Flood A, Thomas W, Gross M, Schmitz KH, Kurzer MS. Consumption of a high glycemic load but not a high glycemic index diet is marginally associated with oxidative stress in young women. Nutr Res. 2015 Jan;35(1):7-13. doi: 10.1016/j.nutres.2014.10.005. Epub 2014 Oct 16.

Smith AJ, Phipps WR, Thomas W, Schmitz KH, Kurzer MS. The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):756-64. doi: 10.1158/1055-9965.EPI-12-1325.

O'Dougherty M, Schmitz KH, Hearst MO, Covelli M, Kurzer MS. Dual conversations: body talk among young women and their social contacts. Qual Health Res. 2011 Sep;21(9):1191-204. doi: 10.1177/1049732311405804. Epub 2011 Apr 20.