Kim C. Westerlind

Effects of aerobic exercise training on estrogen metabolism in premenopausal women: a randomized controlled trial.

Background: Regular physical activity may alter estrogen metabolism, a proposed biomarker of breast cancer risk, by shifting metabolism to favor production of 2-hydroxyestrone (2-OHE1). Few studies, however, have examined this question using a randomized controlled trial. Purpose: To examine the effects of 12 weeks of aerobic exercise training on 2-OHE1 and 16α-hydroxyestrone (16α-OHE1) in premenopausal women. Methods: Participants were healthy, regularly menstruating, Caucasian women, 20 to 35 years, body mass index of 18 to 29.9, not using pharmacologic contraceptives, with average or below average fitness [maximal oxygen consumption (VO2max), <40 mL/kg/min]. Following a baseline menstrual cycle, participants (N = 32) were randomly assigned to a 12-week aerobic exercise training intervention (n = 17) or usual lifestyle (n = 15). Height, body mass, body composition by dual-energy X-ray absorptiometry, and VO2max were measured at baseline and following the intervention. Urine samples were collected in the luteal phase of four consecutive menstrual cycles. Results: The exercise group increased VO2max by 14% and had significant, although modest, improvements in fat and lean body mass. No significant between-group differences were observed, however, for the changes in 2-OHE1 (P = 0.944), 16α-OHE1 (P = 0.411), or the ratio of 2-OHE1 to 16α-OHE1 (P = 0.317). At baseline, there was an inverse association between body fat and 2-OHE1 to 16α-OHE1 ratio (r = −0.40; P = 0.044); however, it was the change in lean body mass over the intervention that was positively associated with a change in 2-OHE1 to 16α-OHE1 ratio (r = 0.43; P = 0.015). Conclusions: A 12-week aerobic exercise training intervention significantly improved aerobic fitness and body composition but did not alter estrogen metabolism in premenopausal women. Interestingly, an increase in lean body mass was associated with a favorable change in 2-OHE1 to 16α-OHE1 ratio. (Cancer Epidemiol Biomarkers Prev 2007;16(4):731–9)

Exercise Effects on Tumorigenesis in a p53-deficient Mouse Model of Breast Cancer

PURPOSEnPhysically active women have a reduced risk of breast cancer, but the dose of activity necessary and the role of energy balance and other potential mechanisms have not been fully explored in animal models. We examined treadmill and wheel running effects on mammary tumorigenesis and biomarkers in p53-deficient (p53(+/-)):MMTV-Wnt-1 transgenic mice.nnnMETHODSnFemale mice (9 wk old) were randomly assigned to the following groups in experiment 1: treadmill exercise 5 d x wk(-1), 45 min x d(-1), 5% grade at 20 m x min(-1), approximately 0.90 km x d(-1) (TREX1, n = 20) or at 24 m x min(-1), approximately 1.08 km x d(-1) (TREX2, n = 21); or a nonexercise control (CON-TREX, n = 22). In experiment 2, mice were randomly assigned to voluntary wheel running (WHL, n = 21, 2.46 +/- 1.11 km x d(-1) (mean +/- SD)) or to a nonexercise control (CON-WHL, n = 22). Body composition was measured at approximately 9 wk and serum insulin-like growth factor 1 (IGF-1) at two to three monthly time points beginning at approximately 9 wk on study. Mice were sacrificed when tumors reached 1.5 cm, mice became moribund, or there was only one mouse per treatment group remaining.nnnRESULTSnTREX1 (24 wk) and TREX2 (21 wk) had shorter median survival times than CON-TREX (34 wk; P < 0.01), whereas those of WHL and CON-WHL were similar (23 vs 24 wk; P = 0.32). TREX2 had increased multiplicity of mammary gland carcinomas compared with CON-TREX; WHL had a higher tumor incidence than CON-WHL. All exercising animals were lighter than their respective controls, and WHL had lower body fat than CON-WHL (P < 0.01). There was no difference in IGF-1 between groups (P > 0.05).nnnCONCLUSIONSnDespite beneficial or no effects on body weight, body fat, or IGF-1, exercise had detrimental effects on tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer.

Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis.

ObjectiveTo investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio.MethodsWe conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method.ResultsWe observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90).ConclusionOur study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.

Alterations in oxygen consumption during and between bouts of level and downhill running.

Since the etiology of the drift in VO2 during downhill running is unclear, this study was designed to assess the contribution of heart rate (HR), ventilation (VE), blood lactate, rectal temperature (RT), muscle damage, and several variables that have not previously been included in VO2 drift research: muscle temperature (MT), and stride rate (SR) and length (SL), to the drift in VO2. Six subjects participated in a 45-min level run (LEVEL) and two 45-min downhill runs (DOWN1 and DOWN2) at 50% VO2max. Although VO2 increased significantly over time for all bouts, the magnitude [4.3% (LEVEL), 5.4% (DOWN1), and 8.1% (DOWN2)] did not differ between bouts (P > 0.05). VO2 was significantly lower during DOWN2 than during LEVEL and DOWN1 (P < 0.05). MT increased during the three bouts (P < 0.05) but the change over time was not different between bouts. SR and SL did not change over time within each bout nor between the two downhill runs. Muscle damage, as indicated by serum creatine kinase levels and perceived soreness, was less following LEVEL and DOWN2 than DOWN1 (P < 0.05). HR and RT increased over time (P < 0.05) but did not differ between bouts. VE and blood lactate did not differ over time or between bouts. VO2 drift during the three bouts paralleled changes in RT, MT, and HR but appears unrelated to muscle damage or biomechanical factors.

Exercise and Serum Androgens in Women

In brief: Little information exists about the role of androgens in women relative to exercise, particularly resistance exercise. This study examines (1) the effect of a ten-week hydraulic resistance exercise program on serum androgen levels, strength, and lean body weight and (2) the relationship of serum androgen levels to strength and lean body weight before and after the ten-week program. Thirteen experimental and five control subjects, all college women, participated. Training did not result in significant increases in androgen hormones, although there were significant gains in strength. In addition, no significant correlations were observed between testosterone, androstenedione, or sex hormone-binding globulin and pretraining and delta values of strength or lean body weight (r <.49).