The effects of glucosamine sulfate on intervertebral disc annulus fibrosus cells in vitro.

BACKGROUND CONTEXT: Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection. PURPOSE: The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading. STUDY DESIGN: Controlled in vitro laboratory setting. METHODS: Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1ß and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM, and the authors have no conflicts of interest. RESULTS: Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose-dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, matrix metalloproteinase-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested. CONCLUSIONS: These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation but not under conditions where mechanical loading is present or in which matrix synthesis is needed.

What midlife women want from gynecologists: a survey of patients in specialty and private practices.

BACKGROUND: This study characterized the self-reported reason for a gynecology visit among midlife women in three different practice settings. We hypothesized that women seeking specialty care were more likely to report nonvasomotor symptoms potentially related to the menopausal transition. METHODS: Participants were 625 women aged 40-60 seen by gynecologists at three sites: an urban, academic, gynecologic menopause practice (Midlife Practice, or MLP) and urban (site A) and suburban (site B) locations of a general, nonacademic obstetrics and gynecology practice. Participants completed a self-report questionnaire asking them to choose and weigh the reason for their visit as "very much," "somewhat," or "not at all" for 15 common gynecologic and menopausal concerns. Demographic questions included age, self-rated health status, race/ethnicity, difficulty of paying for basics, and education. Comparisons between the three groups were made using parametric and nonparametric tests as appropriate. The main outcome measure was the response to the reason for participants' visit compared across the three sites. RESULTS: Women presenting to the MLP were significantly older and more likely to report vasomotor symptoms (VMS), moodiness, sexual problems, sleep problems, and weight and to learn more about menopause. When "very much" and "somewhat" reasons were combined, nearly 80% of the MLP responses listed sleep problems, 60% listed vaginal dryness or low desire, 34% listed weight gain, and 30.7% listed mood. CONCLUSIONS: Midlife women seeking care in a menopause gynecology practice had significantly more visits for vasomotor and nonvasomotor concerns than did women seeing general gynecologists. Women sought care for a broad range of concerns that are not typically in gynecologists' scope of practice, including sleep disturbances, moodiness, and weight management.

Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration.

STUDY DESIGN: Laboratory based controlled in vivo study. OBJECTIVE: To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration. SUMMARY OF BACKGROUND DATA: Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A Centers for Disease Control report from 2009 reported that many patients are using glucosamine supplementation for low back pain, without significant evidence to support its use. Because disc degeneration is a major contributor of low back pain, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. METHODS: Eighteen skeletally mature New Zealand White rabbits were divided into 4 groups: control, annular puncture, glucosamine, and annular puncture + glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107 mg/d (weight based equivalent to human 1500 mg/d). Annular puncture surgery involved puncturing the annulus fibrosus of 3 lumbar discs with a 16-gauge needle to induce degeneration. Serial magnetic resonance images were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan content, relative gene expression measured by real time polymerase chain reaction, and histological analyses. RESULTS: The magnetic resonance imaging index and nucleus pulposus area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and glycosaminoglycan content. Gene expression was consistent with a detrimental effect on matrix. CONCLUSION: These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, magnetic resonance imaging, histology, and total proteoglycan is antianabolic. This raises concern about this commonly used supplement, and future research is needed to establish the clinical relevance of these findings.

Yoga and quality-of-life improvement in patients with breast cancer: a literature review.

OBJECTIVE: Women undergoing treatment for breast cancer often turn to complementary and alternative medicine (CAM), including yoga, for improvement of mood, quality of life (QOL), sleep, and treatment-related side effects. The extant literature was reviewed to examine the clinical effects of yoga practice on QOL for patients with breast cancer. QOL was defined as physical well-being, social functioning, emotional health, and function-al adaptation. METHODS: Seven databases, including PubMed, Ovid MEDLINE, CINAHL, Embase, PsycINFO, Cochrane Library, and Web of Science were used to search for studies of patients with breast cancer that included a yoga intervention and QOL assessment. Attention was paid to assessing study population, outcome variables, the type of yoga intervention used, and methodological strengths and limitations. RESULTS: Seventy-one articles were identified that fit the search criteria. Although the literature provided evidence of QOL benefits of yoga for patients with breast cancer, no specific aspect of yoga was identified as being most advantageous. CONCLUSION: Although participation in yoga programs appeared to benefit patients with breast cancer, greater methodological rigor is required to understand the mechanisms that contribute to their effectiveness.

Pilot study of yoga for breast cancer survivors with poor quality of life.

INTRODUCTION: Studies show benefits of yoga for breast cancer patients with poor quality of life (QOL); however, none exclusively focus on survivors. This study addresses whether hatha yoga improves breast cancer survivors' QOL. METHODS: 25 breast cancer survivors completed six weeks of yoga. Outcome measures were 5 QOL categories evaluated using the FACT-B survey pre and post-intervention and after 6 months. RESULTS: Each category was evaluated independently, including: physical (PWB), social (SWB), emotional (EWB), functional (FWB), breast cancer specific well-being (BCS), Trial Outcome Index (TOI), FACT-G, and FACT-B. Significant improvement was found in all categories except social well-being (PWB p = .013, EWB p = .005, FWB p = .003, BCS p < .001, TOI p < .001, FACT-G p = .004, FACT-B p < .001). Patients with below average pre-intervention index scores (n = 13) showed greater improvement in EWB and FWB, while those with above average pre-intervention scores (n = 9) showed greater improvement in PWB. CONCLUSIONS: Yoga may be feasible and clinically useful for breast cancer survivors with poor QOL.

Effect of Sahaja yoga meditation on quality of life, anxiety, and blood pressure control.

OBJECTIVE: The present study investigates the effect of Sahaja yoga meditation on quality of life, anxiety, and blood pressure control. DESIGN: The prospective observational cohort study enrolled two study groups: those receiving treatment from the International Sahaja Yoga Research and Health Center (meditation group) and those receiving treatment from the Mahatma Gandhi Mission Hospital (control group). Researchers measured quality of life, anxiety, and blood pressure before and after treatment. RESULTS: Sixty-seven (67) participants in the meditation group and 62 participants in the control group completed the study. The two groups were comparable in demographic and clinical characteristics. At baseline, the meditation group had higher quality of life (p<0.001) than controls but similar anxiety level (p=0.74) to controls. Within-group pre- versus post-treatment comparisons showed significant improvement in quality of life, anxiety, and blood pressure in the meditation group (p<0.001), while in controls, quality of life deteriorated and there was no improvement in blood pressure. The improvement in quality of life, anxiety reduction, and blood pressure control was greater in the meditation group. The beneficial effect of meditation remained significant after adjusting for confounders. CONCLUSIONS: Meditation treatment was associated with significant improvements in quality of life, anxiety reduction, and blood pressure control.

Melatonin osteoporosis prevention study (MOPS): a randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women.

The purpose of this double-blind study was to assess the effects of nightly melatonin supplementation on bone health and quality of life in perimenopausal women. A total of 18 women (ages 45-54) were randomized to receive melatonin (3mg, p.o., n=13) or placebo (n=5) nightly for 6months. Bone density was measured by calcaneal ultrasound. Bone turnover marker (osteocalcin, OC for bone formation and NTX for bone resorption) levels were measured bimonthly in serum. Participants completed Menopause-Specific Quality of Life-Intervention (MENQOL) and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after treatment. Subjects also kept daily diaries recording menstrual cycling, well-being, and sleep patterns. The results from this study showed no significant change (6-month-baseline) in bone density, NTX, or OC between groups; however, the ratio of NTX:OC trended downward over time toward a ratio of 1:1 in the melatonin group. Melatonin had no effect on vasomotor, psychosocial, or sexual MENQOL domain scores; however, it did improve physical domain scores compared to placebo (mean change melatonin: -0.6 versus placebo: 0.1, P<0.05). Menstrual cycling was reduced in women taking melatonin (mean cycles melatonin: 4.3 versus placebo: 6.5, P<0.05), and days between cycles were longer (mean days melatonin: 51.2 versus placebo: 24.1, P<0.05). No differences in duration of menses occurred between groups. The overall PSQI score and average number of hours slept were similar between groups. These findings show that melatonin supplementation was well tolerated, improved physical symptoms associated with perimenopause, and may restore imbalances in bone remodeling to prevent bone loss. Further investigation is warranted.

Revisiting the Sham: Is It all Smoke and Mirrors?

The misuse of sham controls in examining the efficacy or effectiveness of Complementary and Alternative Medicine has created numerous problems. The theoretical justification for incorporating a sham is questionable. The sham does not improve our control of bias and leads to relativistic data that, in most instances, has no appropriate interpretation with regards to treatment efficacy. Even the concept of a sham or placebo control in an efficacy trial is inherently paradoxical. Therefore, it is prudent to re-examine how we view sham controls in the context of medical research. Extreme caution should be used in giving weight to any sham-controlled study claiming to establish efficacy or safety.

The relationship between perceived stress, acupuncture, and pregnancy rates among IVF patients: a pilot study.

UNLABELLED: The aim of this paper was to determine the effect of acupuncture on perceived stress levels in women on the day of embryo transfer (ET), and to determine if perceived stress levels at embryo transfer correlated with pregnancy rates. The study was an observational, prospective, cohort study based at the University IVF center. PATIENT(S): 57 infertile patients undergoing IVF or IVF/ICSI. INTERVENTIONS(S): Patients were undergoing Embryo Transfer with or without acupuncture as part of their standard clinical care. MAIN OUTCOME MEASURE(S): Perceive Stress Scale scores, pregnancy rates. RESULT(S): women who received this acupuncture regimen achieved pregnancy 64.7%, whereas those without acupuncture achieved pregnancy 42.5%. When stratified by donor recipient status, only non-donor recipients potentially had an improvement with acupuncture (35.5% without acupuncture vs. 55.6% with acupuncture). Those who received this acupuncture regimen had lower stress scores both pre-ET and post-ET compared to those who did not. Those with decreased their perceived stress scores compared to baseline had higher pregnancy rates than those who did not demonstrate this decrease, regardless of acupuncture status. CONCLUSIONS(S): The acupuncture regimen was associated with less stress both before and after embryo transfer, and it possibly improved pregnancy rates. Lower perceived stress at the time of embryo transfer may play a role in an improved pregnancy rate.

Prophylactic bilateral oophorectomy or removal of remaining ovary at the time of hysterectomy in the United States, 1979-2004.

OBJECTIVE: The purpose of this study was to describe national rates and trends of prophylactic bilateral oophorectomy or remaining oophorectomy (BO/RO) at hysterectomy in women without specific gynecologic disease. STUDY DESIGN: Data from the National Hospital Discharge Survey were analyzed for 1979-2004. Hysterectomies were divided into 2 groups: (1) hysterectomy with BO/RO and (2) hysterectomy alone (> or =1 ovary remaining). Age-adjusted rates (AARs) were calculated with 2000 US census data. RESULTS: Approximately 3,686,000 hysterectomies with BO/RO were performed from 1979-2004. AARs of hysterectomy with BO/RO decreased during this period; the AARs in women > or =50 years old increased. The number of hysterectomies alone was 5,461,100, and AARs of hysterectomy alone decreased significantly from 2.9 per 1000 women in from 1979-1981 to 1.1 per 1000 women in 2001 (P < .001). The proportion of women who underwent hysterectomy with BO/RO increased from 29% in 1979 to 45% in 2004. CONCLUSION: Although AARs of prophylactic BO/RO decreased from 1979-2004, the actual proportion of BO/RO at hysterectomy increased.

Brief relaxation training program for hospital employees.

Employee stress leads to attrition, burnout, and increased medical costs. We aimed to assess if relaxation training leads to decreased stress levels based on questionnaire and thermal biofeedback. Thirty-minute relaxation training sessions were conducted for hospital employees and for cancer patients. Perceived Stress levels and skin temperature were analyzed before and after relaxation training.

Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue.

Cancer-related fatigue is a substantial problem for cancer patients and their caregivers, but no effective treatment exists. Acupuncture has been suggested to improve cancer-related fatigue, but no randomized clinical trials have been conducted. We hypothesized that true acupuncture, compared with sham acupuncture, would reduce cancer-related fatigue in cancer patients receiving external radiation therapy. The aim of this study was to determine effect size and feasibility. A modified, double-blind, randomized, placebo-controlled trial was conducted. The subject, clinical staff, and assessor were blinded, but the acupuncturist was not. Subjects received acupuncture once to twice per week during the 6-week course of radiation therapy. Data were collected at baseline, 3 weeks, 6 weeks, and 10 weeks, which was 4 weeks after that last radiation session. Twenty-seven subjects enrolled, and 23 completed the last data collection. Both true and sham acupuncture groups had improved fatigue, fatigue distress, quality of life, and depression from baseline to 10 weeks, but the differences between the groups were not statistically significant. The true acupuncture group improved 5.50 (SE, +/- 1.48) points on the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F), whereas the sham acupuncture group improved by 3.73 (SE +/- 1.92) points. This difference was not statistically significant (p = .37). All subjects guessed that they were in the true acupuncture group. Our study was underpowered to find a statistically significant difference. To demonstrate a statistically significant improvement between true and sham acupuncture would require 75 subjects per group in a future study. Owing to poor recruitment, the feasibility of a larger trial using the same methodology is low. Despite being underpowered, it appears that subjects receiving true acupuncture may benefit more than subjects receiving sham acupuncture. In the discussion section, we review our experience with using a sham-needle controlled study.

Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of intravaginal estriol and progesterone on atrophic vaginitis in postmenopausal women. METHODS: Under a physician-sponsored Investigational New Drug application, 19 healthy postmenopausal women with atrophic vaginitis received vaginal suppositories containing estriol (1 mg) and progesterone (30 mg). The participants were instructed to insert one suppository intravaginally once daily for 2 weeks and thrice weekly for a total of 6 months. Vaginal pH, Vaginal Maturation Index, urinalysis, self-reported vaginal dryness, menopausal quality of life, and serum estriol and progesterone levels were measured at enrollment and after 3 and 6 months of suppository use. Endometrial biopsies were obtained at enrollment and at 6 months. After 2 weeks of therapy, six participants had serum estriol and progesterone measured. RESULTS: The Vaginal Maturation Index, vaginal pH, and vaginal dryness rating improved significantly at 3 and 6 months compared with baseline. Menopausal quality of life scores improved significantly in all domains, with the sexual subscale showing the most improvement. There were no cases of endometrial hyperplasia after 6 months of suppository use. Serum preinsertion estriol at week 2 and months 3 and 6 were similar to baseline levels. Serum preinsertion progesterone increased but returned to baseline preinsertion levels at month 6, and preinsertion levels were significantly less at month 6 compared with month 3. CONCLUSIONS: Intravaginal administration of a combination estriol and progesterone agent to women with atrophic vaginitis may represent a safe and effective alternative to systemic hormone replacement, although this study was not adequate to provide proof of efficacy given that it was uncontrolled.

Endometrial hyperplasia, endometrial cancer and prevention: gaps in existing research of modifiable risk factors.

PURPOSE: Endometrial carcinoma is the most common cancer of the lower female genital tract in Europe and the United States. Faced with the growing incidence of endometrial cancer in Europe and around the world, scientists, doctors and public health professionals are becoming more concerned with identifying effective preventive measures for this condition. This review paper presents the existing knowledge about modifiable risk factors leading to endometrial hyperplasia and endometrial cancer and highlights the need for more studies in this area. DESIGN/METHODS: Extensive literature review of modifiable risk factors for endometrial cancer and endometrial hyperplasia has been performed. Additionally, biomarker approaches to cancer monitoring, existing therapies for endometrial hyperplasia and factors affecting patient survival are reviewed. RESULTS: Obesity and inactivity are two of the major risk factors associated with the development of endometrial cancer and endometrial hyperplasia. Other modifiable risk factors include dietary habits, exercise and the use of hormonal therapy. Similar factors, along with cancer biomarkers, may play an important role in the early detection of endometrial cancer and survival after the diagnosis. The majority of these factors fit well with the unopposed oestrogen theory. Diet and exercise programmes are currently not integrated into a standard treatment programmes for patients with endometrial hyperplasia or endometrial cancer. CONCLUSIONS: More studies are needed to investigate modifiable risk factors for endometrial cancer and endometrial hyperplasia. Existing therapies for endometrial hyperplasia target hormone imbalance, which is just one aspect of endometrial cancer development. Next generation therapies for endometrial cancer and endometrial hyperplasia patients should include diet, exercise and weight loss plans, which would target other modifiable aspects of endometrial cancer risk.

Nutrient involvement in preeclampsia.

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed by new-onset increased blood pressure and proteinuria during gestation; for many years these markers were the sole targets for study. More recently, increased attention to the multisystemic nature of the syndrome with involvement of almost all organs, activation of coagulation and increased sensitivity to pressor agents has expanded understanding of the disorder. The epidemiology of preeclampsia, being more common in poor women, long ago suggested that nutrients might be involved in the disorder. Numerous conflicting hypotheses were advanced but the testing of these hypotheses has either been done poorly or not at all. Review of the available data indicates very few studies that provide useful insights. In many studies the syndrome is poorly defined and in most studies nutritional data (questionnaires or biomarkers) are obtained on women with the clinical syndrome. In overtly preeclamptic women it is impossible to decipher cause from effect. Nonetheless, current concepts of the genesis of preeclampsia that include endothelial dysfunction, inflammatory activation, oxidative stress and predisposing maternal factors provide targets for well-designed nutritional investigation. In this review the current concepts of the pathogenesis of preeclampsia are reviewed and available data are assessed in light of these concepts. Targets for nutritional investigation based on the current knowledge of pathophysiology are suggested.

A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium.

OBJECTIVE: This study was designed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy, to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms, and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology. METHODS: We performed a prospective, double-blinded, randomized, placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplementation versus placebo in postmenopausal women. Baseline endometrial biopsies were performed and, if adequate, nonhyperplastic, noncancerous, and nonovulatory, subjects were randomly assigned to receive daily placebo or soy cereal supplementation for 6 months. Study subjects completed baseline and weekly dietary, symptom, and side effect logs. Repeat endometrial biopsies were obtained at 6 months. RESULTS: Subjects were recruited from January 1998 through June 2000. Twenty-seven subjects were randomized, and 19 completed the study. One (3.7%) baseline endometrial sample was weakly proliferative. All other baseline and final biopsies were consistent with atrophic, inactive endometrium. The maximum risk of endometrial stimulation with phytoestrogens is 35%. Hot flushes, night sweats, and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group. Insomnia was more common in the treated group. There were no other statistically significant differences in symptoms or side effects. CONCLUSION: Phytoestrogens did not cause stimulation of the endometrium. Insomnia was more frequent over the 6-month study in the soy group, whereas hot flushes, night sweats, and vaginal dryness improved from baseline in the placebo group but not in the soy group.