Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients

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Abstract

Objectives: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, and levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS) and melatonin.

Methods: Fifty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week Mindfulness-Based Stress Reduction (MBSR) program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life, mood, stress, and the hormone measures of salivary cortisol (assessed three times/day), plasma DHEAS, and salivary melatonin were assessed pre- and post-intervention.

Results: Fifty-eight and 42 patients were assessed pre- and post-intervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality, but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice. No significant improvements were seen in mood disturbance. Improvements in quality of life were associated with decreases in afternoon cortisol levels, but not with morning or evening levels. Changes in stress symptoms or mood were not related to changes in hormone levels. Approximately 40% of the sample demonstrated abnormal cortisol secretion patterns both pre- and post-intervention, but within that group patterns shifted from “inverted-V-shaped” patterns towards more “V-shaped” patterns of secretion. No overall changes in DHEAS or melatonin were found, but nonsignificant shifts in DHEAS patterns were consistent with healthier profiles for both men and women.

Conclusions: MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients, and resulted in possibly beneficial changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. These pilot data represent a preliminary investigation of the relationships between MBSR program participation and hormone levels, highlighting the need for better-controlled studies in this area.

Introduction

Recently, there has been a growth of clinical treatment and wellness programs based on mindfulness meditation and yoga modeled after the Mindfulness-Based Stress Reduction (MBSR) program of Jon Kabat-Zinn and colleagues at the Stress Reduction Clinic of the University of Massachusetts Medical Centre (Kabat-Zinn, 1990). Since their initial inception in 1979, there are now over 240 such programs across North America.

MBSR is rooted in the contemplative spiritual traditions in which the experience of conscious awareness is actively cultivated. Within a framework of non-judging, acceptance, and patience, meditative practice often focuses awareness on one’s own breathing. Typically, this leads to a state of relaxation and alert observant detachment. The body of research investigating MBSR’s efficacy for the treatment of health problems has also grown. Studies have shown its efficacy for problems as various as chronic pain (Kabat-Zinn, 1982, Kabat-Zinn et al., 1987), anxiety disorders (Kabat-Zinn et al., 1992, Miller et al., 1995), fibromyalgia (Kaplan et al., 1993, Singh et al., 1998), epilepsy (Deepak et al., 1994), psoriasis (Kabat-Zinn et al., 1998), and hypertension (Schneider et al., 1995). Enhancement of health-related quality of life with improved vitality, less bodily pain, fewer role limitations caused by physical health, greater social functioning, and decreased anxiety and depression have been shown recently in a group of mixed diagnosis medical patients (Reibel et al., 2001).

Considering the high degree of emotional distress following receipt of a cancer diagnosis (Strain, 1998, Derogatis et al., 1983, Zabora et al., 1997), and the efficacy of MBSR in other medical populations, it seemed logical to offer the MBSR program to cancer patients. Indeed, within the population of cancer patients, there is a growing interest in mind–body medicine and complementary and alternative therapies, as well as a desire to be proactive and take initiative in personal care (Cassileth and Chapman, 1998; Ernst and Cassileth, 1998). Thus, the MBSR program provides not only an efficacious treatment for distress, but fits with patients’ own framework of positive health behavior. Our initial work with MBSR showed substantial improvements in symptoms of stress and mood disturbance in a randomized controlled trial of a mixed group of cancer patients (Speca et al., 2000), which were maintained six months later (Carlson et al., 2001). Another report of results on immune system parameters from the current study is in press (Carlson et al., in press). Here, we focus on the effects of the program on hormone levels.

Cortisol, the primary stress hormone secreted from the adrenals, is known to have immunosuppressive effects (for reviews, see Andersen et al., 1994, Cohen and Williamson, 1991, Spiegel et al., 1998) and is largely responsible for the downregulation of immune function as a result of stress. Its hypersecretion may also result in depressed mood (Sikes and Lasley, 1989, Wolkowitz, 1994). Additionally, cortisol levels have been reported to be elevated in breast cancer patients both prior to and following treatment (Aragona et al., 1996, van der Pompe et al., 1997, McEwen and Sapolsky, 1995). Abnormal patterns of cortisol secretion have also been reported in up to 75% of a sample of metastatic breast and ovarian cancer patients (Touitou et al., 1996). The slope of the rate of change of cortisol levels throughout the day was associated with survival time in a group of women with metastatic breast cancer, with those women who displayed less variation in cortisol levels, expressed as a flatter slope, experiencing earlier mortality (Sephton et al., 2000). This relationship held even when other prognostic medical variables were taken into account. The authors speculate that these abnormal circadian rhythms of cortisol secretion represent compromised hypothalamic–pituitary–adrenal (HPA) axis functioning, which may be responsible for the earlier mortality. Indeed, other studies have found that circadian abnormalities had prognostic value in predicting initial occurrences of breast cancer (Ticher et al., 1996), as well as associations with later stages of cancer development and with other prognostic indicators (Mormont and Levi, 1997, Touitou et al., 1996).

Meditation has been shown to decrease cortisol levels in populations of healthy volunteers (MacLean et al., 1994, Sudsuang et al., 1991), but the effect of meditation training or the MBSR program on cortisol levels has not previously been evaluated in people with cancer. However, there has been some investigation of the effects of other types of psychosocial intervention on cortisol levels in cancer patients. One study of a 10-week behavioral intervention for early stage breast cancer patients combined relaxation techniques, information about the mind–body connection, health education, and coping skills (Schedlowski et al., 1994). Decreases in cortisol levels in the intervention compared to the control group were seen within two weeks, and these differences were maintained at the end of the intervention. However, women were not randomly assigned to groups, and plasma samples of cortisol were collected only in the evenings. A randomized trial of an experiential–existential therapy intervention including relaxation, emotional self-disclosure, and social support provided to later stage breast cancer patients reported decreases in levels of cortisol post-intervention in the treatment group, but only for those who had high levels of cortisol at the start of the program (van der Pompe et al., 1997). Again, only one measure of plasma cortisol was taken at each test time, and in this case the time of day was not specified and presumably not controlled. Another study that randomly assigned women with early stage breast cancer to a post-surgery 10-week cognitive-behavioral stress management intervention found decreased cortisol levels that were related to increases in the ability to find positive benefits of the breast cancer experience (Cruess et al., 2000). As in the other studies, one sample of plasma cortisol was obtained at each assessment period, at 18:00 h in this case. Improving on these designs, in the current study, cortisol was assessed at three time periods both pre- and post-intervention. Salivary cortisol measurement was used, as it is more convenient for multiple daily assessment, and has been shown to accurately reflect blood levels (Kirschbaum and Hellhammer, 1994). The method of using cotton collection swabs has also been shown not to affect the validity of cortisol immunoassays (Shirtcliff et al., 2001)

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), too, are adrenal hormones, androgens that have antiglucocorticoid properties on cells of the immune system (Blauer et al., 1991). DHEAS is more commonly measured than DHEA due to its much higher blood levels, long half-life, and most importantly, its absence of diurnal variation, making it possible to take only one blood sample and attain an accurate reading regardless of the time of day (Hornsby, 1995). DHEAS is the most abundant product of the adrenal gland and has been identified as the most prevalent steroid hormones in the brains of both rats and humans, where it was found upon postmortem analysis at levels many times higher than in the plasma (Majewska, 1995), although the CSF levels of DHEAS in humans were reported as much lower than those in the blood (Guazzo et al., 1996). In both men and women, DHEAS is derived almost exclusively from the adrenal gland and shows tremendous variation throughout the lifespan and between individuals, with systemic age-related decreases (Vermeulen, 1995). Higher levels of DHEAS have been associated with enhanced immune function and mood in humans (Morales et al., 1994), although not all studies have found lower DHEAS levels in depressed patients (Heuser et al., 1998, Wolkowitz et al., 1997, Morales et al., 1994). A study of healthy long-term meditation practitioners found higher levels of DHEAS and lower levels of cortisol compared to healthy controls (Walton et al., 1995), and in the women practising meditation, cortisol correlated inversely, and DHEAS directly, with months of meditation practice. Another study found higher DHEAS in meditators compared to non-meditators in all age groups for women, but only in the older men, suggesting a modification of the age-related decreases in DHEAS for males (Glaser et al., 1992). In terms of intervention effects, in a group of HIV positive men who participated in a 10-week cognitive-behavioral stress reduction intervention, the ratio of cortisol/DHEAS increased, and was associated with changes in mood disturbance over the course of the intervention (Cruess et al., 1999). DHEAS measurement in the current study was done via serum, since only one sample was required.

The pineal hormone melatonin has been implicated recently in the development and treatment of many types of cancers (Kanno et al., 1997, Esterling et al., 1996). Animal research has shown it to be immune enhancing, increasing T lymphocyte proliferation and NK cell response to the mitogen concanavalin (Liebmann et al., 1997). Melatonin also has oncostatic actions, suppressing tumor growth and even shrinking the size of tumors in vitro (Cos et al., 1998). In humans, a series of clinical trials using melatonin in conjunction with standard treatment found superior survival response in patients with advanced cancer receiving adjuvant melatonin (Lissoni et al., 1999a), and higher tolerance of standard chemotherapy regimes (Lissoni et al., 1999b, Lissoni et al., 1997). A recent large review in the Journal of Clinical Oncology concluded that converging evidence points to antioxidant and oncostatic actions of melatonin and provides a rationale for large transnational research-based clinical trials of melatonin therapy for a wide variety of cancers (Vijayalaxmi et al., 2002). Considering this growing body of evidence implicating melatonin as a potentially important factor in carcinogenesis, the demonstration in healthy people that consistent meditators produced higher levels of melatonin after a night-time meditation session compared to a control night (Tooley et al., 2000, Henderson, 1989), and that meditation practice in breast cancer patients was effective in increasing melatonin levels (Massion et al., 1995), is provocative. Melatonin was measured in this study via salivary assays. Studies have shown very high correlations between plasma and salivary levels of melatonin, using cotton saliva collection techniques (Voultsios et al., 1997, Laakso et al., 1990, McIntyre et al., 1987). The convergence of this endocrinological research suggests that the measurement of cortisol, DHEAS, and melatonin may be important to understand the mechanisms underlying the physiological effects of these psychosocial interventions.

This paper reports the results of pre–post-intervention study of an eight-week MBSR intervention provided to breast and prostate cancer patients. We focused on breast and prostate patients because these two cancers have similar good prognoses in the early disease stages, and a similar, although often differently expressed, degree of physical and psychological impairment (DeFlorio and Masie, 1995, Keller and Henrich, 1999, Riska and Ettorre, 1999). Both cancers are also often hormonally dependent, and thought to be responsive to psychosocial intervention. In addition, breast and prostate cancer are the most prevalent carcinomas reported today in women and men, respectively (National Cancer Institute of Canada, 2001). The outcome variables of quality of life, stress symptoms, mood, and the hormonal measures of cortisol, DHEAS, and melatonin are reported. Results of the same trial on immune function are currently in press (Carlson et al., in press).

Section snippets

Subjects

Patients were eligible to participate in the study if they met the following inclusion criteria: (1) age 18 years or older; (2) a diagnosis of Stage 0, I, or II breast or early stage (localized to the prostate) prostate cancer at any time in the past (using standardized TNM diagnostic criteria); and (3) a minimum of three months since surgery (mastectomy/lumpectomy/prostatectomy/cryotherapy). Exclusion criteria were: (1) treatment with chemotherapy, radiation therapy, or hormone therapy (except

Subjects

Demographic characteristics and health behaviors of participants at time 1 are presented in Table 1. Most participants were 50 years of age or older, mean 54.5 years, SD 10.9 years. Most (n=42) were married or co-habiting at the time of study entry. Participants were generally well-educated, with a mean of 14.7 years of formal education. They had been diagnosed with cancer a median of 1.1 years previously (range 3 months–20 years). Six participants were greater than five years post-diagnosis.

Discussion

The results of this pre–post-intervention study indicate that this eight-week mindfulness-based stress reduction program was effective in decreasing symptoms of stress and improving overall quality of life in this group of breast and prostate cancer patients. No change was seen on the POMS scores of these patients, which may be explained by the low level of initial mood disturbance. In fact, the initial level of total mood disturbance in this sample was similar to the post-intervention level of

Acknowledgements

This study was supported by the Canadian Breast Cancer Research Initiative. Dr. Linda Carlson was a Terry Fox Postdoctoral Research Fellow of the National Cancer Institute of Canada during the time the study was conducted. She is currently a Canadian Institutes of Health Research New Investigator. Heartfelt thanks to all the men and women who participated in the study, whose enthusiasm continues to inspire us. Special thanks to our research nurse, Ms. Lori Tillotson, for her tireless efforts in

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