Randomized Exercise Intervention Trial Research Articles

L-Thyroxine intake as a potential risk factor for the development of fatigue in breast cancer patients undergoing chemotherapy.

L-Thyroxine is one of the most commonly prescribed drugs and accordingly used by many breast cancer patients with thyroid disorders. Hence, potential interactions of chemotherapy with L-thyroxine, possibly contributing to fatigue, would be of high clinical relevance. Therefore, we investigated fatigue and underlying pathways in L-thyroxine-using breast cancer patients during chemotherapy. Thyroid-stimulating hormone (TSH), L-triiodothyronine (T3), and diurnal salivary cortisol patterns were analyzed in breast cancer patients in the beginning and at the end of adjuvant chemotherapy within the control group (n = 41) of a randomized exercise intervention trial. Additionally, relationships in the exercising group (n = 45) as well as in healthy women (n = 25) were explored. Regression and mediation analyses were performed. L-Thyroxine use was significantly associated with lower TSH (median = 0.33mU/l, interquartile range = (0.15-0.48)), whereas patients not using L-thyroxine had TSH comparable to healthy women (0.51mU/l (0.37-0.74)). T3 significantly declined during chemotherapy in L-thyroxine users but not in non-users. However, the group difference failed statistical significance. L-Thyroxine treatment was significantly associated with increased physical fatigue during chemotherapy (p = 0.004) in the non-exercising group. This association appeared to be partly mediated by TSH. Further, TSH appeared to affect fatigue partly via increased cortisol levels. In the exercise group, there was no significant association between L-thyroxine and fatigue. L-Thyroxine treatment during chemotherapy might result in hormonal dysregulations that can contribute to increased physical fatigue. Therefore, breast cancer patients on L-thyroxine treatment may need special monitoring of their thyroid levels and of fatigue during chemotherapy and should be encouraged to exercise. ClinicalTrials.gov NCT01106820.

The effect of sleep pattern changes on postpartum depressive symptoms

BackgroundResearch indicates that poor sleep is associated with postpartum depression; however, little is known regarding this relationship among postpartum women who are at high for postpartum depression. This study examined the relationship between changes in self-reported sleep patterns (from six weeks to seven months postpartum) and depressive symptoms at seven months postpartum among women who were at high risk for postpartum depression.MethodsParticipants (n = 122) were postpartum women who were at an increased risk for postpartum depression (personal or maternal history of depression) and had participated in a randomized exercise intervention trial. For the current trial, participants completed the Pittsburgh Sleep Quality Index and Patient Health Questionnaire-9 (PHQ-9; assessed depression) at six weeks and seven months postpartum.ResultsOverall, sleep problems significantly improved from six weeks to seven months postpartum. However, linear regression analyses indicated that worsening or minimal improvement of sleep problems were associated with higher depressive symptoms at seven month postpartum. Regarding the specific types of sleep problems, self-reported changes in sleep latency (i.e., how long it takes to fall asleep at night), daytime dysfunction (i.e., difficulty staying awake during the day), and sleep quality (i.e., subjective rating of sleep quality) were associated with higher levels of depressive symptoms.ConclusionsSleep problems typically improve during the postpartum phase. However, postpartum women who are at high risk for postpartum depression are at an increased risk for depressive symptoms later in the postpartum phase if sleep problems worsen or show only minimal improvement over time. Therefore, at the six-week postpartum clinic visit, women should receive education regarding potential worsening of sleep patterns and strategies for preventing sleep-related problems.Trial registrationRegistered with ClinicalTrials.gov (NCT00961402) on August 18, 2009 prior to the start of the trial.

Effects Of Exercise On Sleep Problems In Breast Cancer Patients Receiving Radiotherapy

Sleep problems frequently affect breast cancer patients during and after treatment and reduce their quality of life. However, coping and treatment strategies are mostly unknown or understudied. Only few studies have investigated the effect of exercise on sleep quality, particularly during the course of radiotherapy. PURPOSE: To assess within a large randomized controlled trial whether a 12-week exercise program starting with the radiotherapy influences sleep trajectories. METHODS: Sleep problems were assessed via self-report in 160 breast cancer patients before, during, and 3,6 and 12 months after they participated in a trial investigating 12-week resistance exercise versus a relaxation control group concomitant to adjuvant radiotherapy (BEST-Study, NCT01568766). In addition, 25 age-matched women without cancer were exercising and followed the same study protocol for comparison purposes. RESULTS: Ordinal logistic regression analyses revealed significant exercise intervention effects regarding the changes in sleep problems (scale: 0–100) from baseline to the end of radiotherapy (mean between-group difference (MD): -10.2, p=0.03) and to the end of intervention (MD= -10.9, p=0.01), with sleep problems decreasing in the exercise group and increasing in the control group. At 12 months, differences were still observed but were statistically non-significant (MD=-5.9, p=0.3). Further adjustment for potential confounders did not change the results. The course of sleep problems in exercising women during the exercising phase was similar in breast cancer patients and in healthy exercisers, yet, patients experienced significantly higher levels of sleep problems at all times. CONCLUSIONS: Our large randomized exercise intervention trial confirmed results from earlier but mostly small studies that radiotherapy aggravates sleep problems in breast cancer patients and that exercise represents an effective treatment option. Given the strong link between quality of life and sleep problems, our finding that a 12-week resistance training for breast cancer patients undergoing radiotherapy reduces sleep problems is of high importance for many cancer patients.

Self-reported physical activity behavior of breast cancer survivors during and after adjuvant therapy: 12 months follow-up of two randomized exercise intervention trials

Background: Exercise during and after breast cancer treatment has shown several health benefits. However, little is known about the courses, patterns, and determinants of physical activity of breast cancer patients, and the role of exercise interventions on their physical activity behavior in the long run.Material and methods: Self-reported physical activity was assessed in 227 breast cancer survivors before, during, and three, six, and 12 months post-intervention within two randomized resistance exercise trials performed during adjuvant chemo- or radiotherapy, respectively, with similar designs. Multiple ordinal logistic regression analyses were performed to identify determinants of physical activity at these time points.Results: While the intervention group exercised a median 1.8 h/week during adjuvant therapy (interquartile range 1.4–2.5), 68% of controls did not engage in any exercise. At 12-months follow-up 32% of patients did not engage in any exercise irrespective of the intervention. Of the patients who cycled for transportation pre-diagnosis about half stopped cycling in the long term in both groups. In contrast, walking was maintained over time. Major determinants of low levels of exercise at 12-months follow-up were low pre-diagnosis levels of exercise, lower education, being postmenopausal, and having breast problems or depressive symptoms. Further, the intervention appeared to influence the type of sports performed, with strength exercise being the most common type of exercise at follow-up in the exercise group, more frequently compared to the control group.Conclusion: The exercise intervention effectively countervailed the decrease in physical activity during cancer therapy and boosted strength exercise in the months following the intervention, but in the longer term many survivors were insufficiently active. Breast cancer survivors may need continued motivation and practical support tailored to their individual characteristics and physical activity history to incorporate exercise in everyday routine in the long term.

Determinants of exercise adherence and contamination in a randomized controlled trial in cancer patients during and after allogeneic HCT.

Evidence from randomized controlled trials is growing that exercise interventions are beneficial in cancer patients receiving allogeneic stem cell transplantation (allo-HCT). However, information about adherence to exercise interventions and exercise contamination in control groups is lacking. This information is crucial for the interpretation of study results. We therefore examined the determinants of exercise adherence and contamination in different treatment periods during (inpatient) and after (outpatient) allo-HCT. One hundred fifty-three patients scheduled for allo-HCT were randomized to a 1-year partly supervised exercise intervention (endurance and resistance exercise) or to a control group. Adherence was assessed via exercise logs and contamination via questionnaires. Adherence varied between 66% (inpatient) and 78% (outpatient) in different treatment periods. During (inpatient) transplantation period, higher adherence was significantly associated with lower fatigue (P = 0.004) and with having children at home (P = 0.049). Adherence after discharge was positively associated with endurance performance (P = 0.003); higher adherence after day 100 was associated with exercise activity prior allo-HCT (P = 0.010) and higher adherence after discharge (P = 0.001). Contamination among controls was high with 54% and significantly associated with muscle strength (P = 0.025) and fatigue (P = 0.050). Exercise adherence in different treatment periods was determined by different variables, and contamination among controls was evident. These findings may have important implications for correct interpretation of randomized exercise intervention trials.

The Relationship between Prenatal Antidepressant Use and the Decision to Breastfeed among Women Enrolled in a Randomized Exercise Intervention Trial.

Despite the numerous health benefits associated with breastfeeding, only 49% of postpartum women in the United States breastfeed at 6 months. Therefore, it is important to understand factors that may influence a woman's decision to breastfeed. The purpose of this study was to examine the relationship between prenatal antidepressant use and the decision to breastfeed among postpartum women. Participants were postpartum women (N = 87) who had participated in a randomized trial examining the efficacy of a 6-month exercise intervention for the prevention of postpartum depression (2009-2012). Participants were recruited from the upper Midwest and were at risk for postpartum depression. Participants completed telephone-based questionnaires assessing their prenatal antidepressant use and breastfeeding behavior. Seventeen percent of the participants took an antidepressant medication during pregnancy and 91% breastfed at birth. After controlling for baseline depressive symptoms, body mass index, and condition assignment, participants who were taking an antidepressant during pregnancy were less likely to initiate breastfeeding than participants who were not taking an antidepressant during pregnancy, β = -2.042, P < .05 (odds ratio = 0.130; 95% confidence interval, 0.024-0.696). Our study indicates that prenatal antidepressant medication use may be a potential barrier to breastfeeding initiation. Additional research is needed to better understand the factors that play a role in the relationship between prenatal antidepressant use and breastfeeding initiation.

Factors influencing participation in a randomized controlled resistance exercise intervention study in breast cancer patients during radiotherapy.

BackgroundOver the past years knowledge about benefits of physical activity after cancer is evolving from randomized exercise intervention trials. However, it has been argued that results may be biased by selective participation. Therefore, we investigated factors influencing participation in a randomized exercise intervention trial for breast cancer patients.MethodsNon-metastatic breast cancer patients were systematically screened for a randomized exercise intervention trial on cancer-related fatigue. Participants and nonparticipants were compared concerning sociodemographic characteristics (age, marital status, living status, travel time to the training facility), clinical data (body-mass-index, tumor stage, tumor size and lymph node status, comorbidities, chemotherapy), fatigue, and physical activity. Reasons for participation or declination were recorded.Results117 patients (52 participants, 65 nonparticipants) were evaluable for analysis. Multiple regression analyses revealed significantly higher odds to decline participation among patients with longer travel time (p = 0.0012), living alone (p = 0.039), with more comorbidities (0.031), previous chemotherapy (p = 0.0066), of age ≥ 70 years (p = 0.025), or being free of fatigue (p = 0.0007). No associations were found with BMI or physical activity. By far the most frequently reported reason for declination of participation was too long commuting time to the training facility.ConclusionsWillingness of breast cancer patients to participate in a randomized exercise intervention study differed by sociodemographic factors and health status. Neither current physical activity level nor BMI appeared to be selective for participation. Reduction of personal inconveniences and time effort, e.g. by decentralized training facilities or flexible training schedules, seem most promising for enhancing participation in exercise intervention trials.Trial registrationRegistered at ClinicalTrials.gov: NCT01468766 (October 2011).

The Role of Physical Activity in Breast Cancer Etiology

Considerable research interest has been given in the past 25 years to examining the role of physical activity in breast cancer prevention given the scarcity of modifiable risk factors for this major cause of cancer incidence and mortality in women. A review of the observational epidemiologic evidence and recent randomized exercise intervention trials on the association between physical activity and breast cancer risk is presented. As of March 2010, 73 separate studies out of 91 publications worldwide were identified as having sufficient data for this review. Across these 73 studies, the average reduction in breast cancer risk, when comparing the most to the least physically active women, was 25%. There also was evidence for a dose-response effect found in the majority of studies that examined this trend. The strongest associations were found for recreational and household activities and for activity that was of at least moderate intensity and sustained over a lifetime. Within population subgroups, a stronger effect was seen in women who are normal weight, in women without a family history of breast cancer, and in women who are parous. Women of all races benefitted from physical activity; however, a particularly strong effect on breast cancer risk was observed in non-Caucasian women. Future research should focus on elucidating the exact type, dose, and timing of physical activity required to reduce breast cancer risk. Prospective observational epidemiologic studies of lifetime physical activity patterns and breast cancer risk would help in this regard, as well as randomized controlled exercise intervention trials employing hypothesized biomarkers of breast cancer risk as outcome measures. Additional consideration to the role of sedentary behavior and light-intensity activity also is needed, as well as improved physical activity assessment methods. These additional data will be useful in improving public health recommendations regarding physical activity for breast cancer risk reduction.

Nonpharmacological approaches to improve bone health and reduce osteoporosis

With an aging population, osteoporosis has become a public health concern and an area of increased awareness among both patients and medical practitioners. Timely screening and pharmacologic treatment of low bone mass effectively reduces fracture risk. Nonpharmacologic interventions, however, deserve equal emphasis both in the prevention and treatment of osteoporosis. Recent advances in bone biology have established that exercise in the form of short, repetitive mechanical loading leads to the greatest gains in bone strength. As demonstrated by both observational and randomized exercise intervention trials, these gains are best achieved in childhood but can be maintained in adulthood with continued regular weight-bearing exercise. In the later years, evidence supports the implementation of balance training to decrease fall risk, especially in elderly patients with low bone mass. Following an osteoporotic fracture, a multidisciplinary rehabilitation program with an emphasis on early mobilization, fall prevention, use of orthoses, and noninvasive surgical procedures is emerging as a promising approach. Clinically, these findings should imply greater emphasis on high impact exercise during skeletal growth and on maintenance of weight bearing and balance training in the later years. Future research should examine the effect of these interventions on fracture prevention.

Aerobic exercise and bone mineral density in middle-aged finnish men: a controlled randomized trial with reference to androgen receptor, aromatase, and estrogen receptor α gene polymorphisms

Our aim was to investigate associations of the polymorphic loci of androgen receptor (AR), aromatase CYP19, and estrogen receptor α (ERα) genes with bone mineral density (BMD) in a four-year controlled randomized exercise intervention trial in Finnish middle-aged men. Additionally, we studied whether the gene polymorphisms affect circulating testosterone (T), estradiol (E 2), and sex hormone-binding globulin concentrations. The polymorphic CAG repeat of the AR gene, the TTTA repeat of the human aromatase gene, and the PvuII site of the ERα gene were analyzed. BMDs of the lumbar spine (L2–L4), femoral neck, and total proximal femur were measured with a dual-energy X-ray absorptiometry (DXA). In the exercise group, the subjects with the ERα gene PP or Pp genotypes showed an increase (+6.5 and +5.1%, respectively) in lumbar spine BMDs ( P = 0.007; repeated measures ANOVA) during intervention, while there was no change in the subjects with the pp genotype. The long TTTA repeat (TTTA 9–12) in aromatase gene was associated with greater height ( P = 0.026) and lower BMI ( P = 0.029) values than the short TTTA repeat (TTTA 6–8). With regard to the AR gene, no statistically significant differences in bone properties were found between the genotypes. There were no significant associations of any analyzed polymorphic sites with the serum sex steroid hormone concentrations in the exercise or reference group. In conclusion, the Finnish middle-aged men with ERα PP or Pp genotypes appear to have increased BMD values in the lumbar spine. This increase may reflect a predisposition to age-related degenerative changes in the spine. In addition, the AR CAG repeat and aromatase TTTA repeat do not modify the effect of regular aerobic exercise on BMD.

Relation of sex hormones to bone mineral density in middle-aged men during a 4 year exercise intervention trial

Recent studies have emphasized the symbiotic role of estradiol and testosterone on bone metabolism. Several anthropomorphic-, lifestyle-, and dual-energy X-ray (DXA)-derived parameters were measured with respect to estradiol (E2), testosterone (T), free T (fT), and sex hormone-binding globulin (SHBG) in 140 men (aged 53–62 years) participating in a controlled, randomized exercise intervention trial. After 4 years of intervention, 132 (94.3%) men remained as participants. During the period of study, aerobic threshold increased significantly in the exercise intervention group compared with the reference group (13.4% vs. −1.9%: p < 0.023). Serum E2 and fT were not convincingly related to bone mineral density (BMD) or BMD change. Aerobic threshold or the change in aerobic threshold were not associated with sex hormone or SHBG levels. Body mass index was a significant determinant of T (β = −0.337), fT (β = −0.293), and SHBG (β = −0.306), and smoking predicted T (β = 0.231) and fT (β = 0.245). Alcohol intake was a significant determinant of E2 (β = 0.213). Ultimately there was no convincing relation between sex hormone levels and BMD or BMD change in middle-aged men.

Dairy Calcium is Related to Changes in Body Composition during a Two-Year Exercise Intervention in Young Women

Objective: Relationships between micronutrients and dairy product intake and changes in body weight and composition over two years were investigated.Design: Two year prospective non-concurrent analysis of the effect of calcium intake on changes in body composition during a two year exercise intervention.Subjects: 54 normal weight young women, 18 to 31 years of age.Measures of Outcome: Mean intakes of nutrients of interest were determined from three-day diet records completed at baseline and every six months for two years. The change in total body weight and body composition (assessed by dual x-ray absorptiometry) from baseline to two years was also determined.Results: Total calcium/kilocalories and vitamin A together predicted (negatively and positively, respectively) changes in body weight (R2 = 0.19) and body fat (R2 = 0.27). Further, there was an interaction of calcium and energy intake in predicting changes in body weight, such that, only at lower energy intakes, calcium intake (not adjusted for energy) predicted changes in body weight.Conclusions: Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial.