Melissa K. Melby

Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials

Objective This analysis was conducted to determine the efficacy of extracted or synthesized soybean isoflavones in the alleviation of hot flashes in perimenopausal and postmenopausal women. Methods PubMed and The Cochrane Controlled Clinical Trials Register Database were searched for relevant articles reporting double-blinded randomized controlled trials through December 14, 2010. References within identified articles, as well as peer-reviewed articles that had come to the attention of the authors through other means, were also examined for suitability. This systematic review and meta-analysis, which evaluated the effects of isoflavones on the frequency, severity, or composite score (frequency × severity) of hot flashes compared with placebo was conducted according to Cochrane Handbook guidelines. Results From 277 potentially relevant publications, 19 trials (reported in 20 articles) were included in the systematic review (13 included hot flash frequency; 10, severity; and 3, composite scores), and 17 trials were selected for meta-analyses to clarify the effect of soybean isoflavones on hot flash frequency (13 trials) and severity (9 trials). Meta-analysis revealed that ingestion of soy isoflavones (median, 54 mg; aglycone equivalents) for 6 weeks to 12 months significantly reduced the frequency (combined fixed-effect and random effects model) of hot flashes by 20.6% (95% CI, −28.38 to −12.86; P < 0.00001) compared with placebo (heterogeneity P = 0.0003, I 2 = 67%; random effects model). Meta-analysis also revealed that isoflavones significantly reduced hot flash severity by 26.2% (95% CI: −42.23 to −10.15, P = 0.001) compared with placebo (heterogeneity, P < 0.00001, I 2 = 86%; random effects model). Isoflavone supplements providing more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements. Conclusions Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.

New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese women.

Objectives: Equol, a metabolite of the isoflavone daidzein, is hypothesized to play a major role in the health benefits of soy. We examined the effect of a new S-equol supplement on menopausal symptoms and mood states. Design: We conducted a randomized, double-blind, placebo-controlled trial with our new equol supplement for 12 weeks with 134 Japanese women (aged 40-59 years). They were randomly assigned to three groups: placebo (n = 44), 10 mg of equol per day (EQ-1; n = 44), and 10 mg of equol three times per day (EQ-3; n = 46). Habitual isoflavone intake was limited to 20 mg/d. Participants completed menopausal symptom and Profile of Mood States questionnaires at baseline and postintervention. Physical examination and blood and 24-hour urine collection were performed at baseline and postintervention. Results: At baseline, total menopausal symptom score varied by menopausal and equol producer status (34.3% producers). A total of 127 participants (94.8%) completed the trial. No adverse effects were reported, except for a systemic rash in one EQ-3 woman. The anxiety scores of equol producers were lower than those of nonproducers (P < 0.05). Significant differences between premenopausal and perimenopausal/postmenopausal symptom scores were observed for anxiety, somatic, and total scores. After the EQ-3 intervention, perimenopausal/postmenopausal equol nonproducers showed significant decreases from baseline in all menopausal symptom scores except depression (P < 0.01). Compared with placebo, the EQ-3 group showed significant decreases in depression scores (P < 0.05), as well as significant decreases in Tension-Anxiety (P < 0.05), Depression-Dejection (P < 0.05) and Fatigue (P < 0.01) and increases in Vigor (P < 0.05) of the Profile of Mood States. Conclusion: S-equol supplement improved mood-related symptoms in perimenopausal/postmenopausal equol nonproducers.

Genistein Affects ERβ- But Not ERα-Dependent Gene Expression in the Hypothalamus

Isoflavone phytoestrogens are growing increasingly popular because of their reported cardiovascular and anticarcinogenic properties, but the effects of these compounds in the brain are largely unknown. In a previous study, we found that an isoflavone supplement, containing a mixture of soy phytoestrogens, inhibited estrogen-dependent female sexual behavior and was antiestrogenic for both ERα- and ERβ-dependent gene expression in the hypothalamus. Here we examined the impact of the soy isoflavone genistein, a major component of the supplement, on estrogen-dependent female sexual behavior and ERα- and ERβ-dependent gene expression in the rat brain. Genistein, at a dietary concentration of 100 or 500 ppm had no effect on lordosis behavior in rats. However, at 500 ppm genistein had differential activity through ERα and ERβ in the hypothalamus. Genistein had no effect, in either the presence or absence of 17β-E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogen-dependen...

Adolescent Sleep Patterns: Toward a Comparative Developmental Ecology of Human Sleep

This exploratory comparative survey of the ecology of human sleep arises from a question posed by a pediatrician who studies mood disorders and sleep (Dahl, 1996; Dahl et al., 1996). In an attempt to gain insights into sleep regulation from ecological theory and research, he questioned what anthropologists know about sleep. The bald, if somewhat overstated, answer was: zero. Sleep, in its ubiquity, seeming nonsociality, apparent universality, and presumed biologically driven uniformity, has been overlooked as a background variable. Amazingly, it has not engaged a discipline dedicated to the study of human behavior, human diversity, and their cultural biological bases. A notable exception is the evolutionary-ethologically informed approach to the anthropological study of sleep pioneered by the work of McKenna and colleagues on sleep arrangements, infant state regulation, and risk for sudden infant death syndrome or SIDS (McKenna, 1991, 1992, 1996; Mosko, McKenna, Dickel, & Hunt, 1993). Harkness and Super have also documented cultural variation in infant sleep in relation to their studies of child care practices (Harkness & Super, 1996; Super, Harkness, van Tijen, van der Vlugt, Fintelman, & Kijksta, 1996), and scattered reports document sleep behavior (Ferreira de Souza Aguiar, Pereira da Sliva, & Margues, 1991).

Soy isoflavones for osteoporosis: An evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.

Effects of soy isoflavone supplements on bone turnover markers in menopausal women: Systematic review and meta-analysis of randomized controlled trials

INTRODUCTION Effects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women. METHODS PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed. RESULTS From 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56 mg soy isoflavones (aglycone equivalents) for 10 weeks to 12 months significantly decreased DPD by 14.1% (95% CI: -26.8% to -1.5%; P=0.03) compared to baseline (heterogeneity: P<0.00001; I(2)=93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of -18.0% (95% CI: -28.4% to -7.7%, P=0.0007; heterogeneity: P=0.0001; I(2)=73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84 mg and 73 mg of soy isoflavones for up to 12 months insignificantly increased BAP by 8.0% (95% CI: -4.2% to 20.2%, P=0.20; heterogeneity: P<0.00001; I(2)=98%) and OC by 10.3% (95% CI: -3.1% to 23.7%, P=0.13; heterogeneity: P=0.002; I(2)=69%) compared with placebo (random effects model), respectively. CONCLUSIONS Soy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers.

Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials.

Objective Reported effects of different soy products on blood pressure vary. This systematic review and meta-analysis was performed to clarify the effects of soy isoflavone extract supplements on systolic and diastolic blood pressure (SBP and DBP) in adult humans. Methods PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant randomized placebo-controlled trials. Study data and indicators of methodological validity were independently extracted by two authors using predefined data fields. Meta-analysis was carried out in Review Manager 5.0.22. Results Searches identified 3740 articles, of which 14 randomized controlled trials (789 participants) were included. Daily ingestion of 25–375 mg soy isoflavones (aglycone equivalents) for 2–24 weeks significantly decreased SBP by 1.92 mmHg (95% confidence interval −3.45 to −0.39; P = 0.01) compared with placebo (heterogeneity P = 0.39, fixed effect model) in adults with normal blood pressure and prehypertension. The effect was not lost on sensitivity analysis. Subgroup analyses suggest greater effects in studies longer than 3 months, in Western populations, at lower doses, and in studies at lower risk of bias. Soy isoflavones did not affect DBP [−0.13 (95% confidence interval −1.03 to 0.78) mmHg, P = 0.78; heterogeneity P = 0.20, fixed effect model]. Conclusion Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans, and no dose–response relationship was observed. Further studies are needed to address factors related to the observed effects of soy isoflavones on SBP and to verify the effect in hypertensive patients.

Methods used in cross-cultural comparisons of somatic symptoms and their determinants

Methodological differences among studies of vasomotor symptoms limit rigorous comparison or systematic review. Vasomotor symptoms generally include hot flushes and night sweats although other associated symptoms exist. Prevalence rates vary between and within populations, but different studies collect data on frequency, bothersomeness, and/or severity using different outcome measures and scales, making comparisons difficult. We reviewed only cross-cultural studies of menopausal symptoms that explicitly examined symptoms in general populations of women in different countries or different ethnic groups in the same country. This resulted in the inclusion of nine studies: Australian/Japanese Midlife Womens Health Study (AJMWHS), Decisions At Menopause Study (DAMeS), Four Major Ethnic Groups (FMEG), Hilo Womens Health Survey (HWHS), Mid-Aged Health in Women from the Indian Subcontinent (MAHWIS), Penn Ovarian Aging Study (POAS), Study of Womens Health Across the Nation (SWAN), Womens Health in Midlife National Study (WHiMNS), and Womens International Study of Health and Sexuality (WISHeS). These studies highlight the methodological challenges involved in conducting multi-population studies, particularly when languages differ, but also highlight the importance of performing multivariate and factor analyses. Significant cultural differences in one or more vasomotor symptoms were observed in 8 of 9 studies, and symptoms were influenced by the following determinants: menopausal status, hormones (and variance), age (or actually, the square of age, age(2)), BMI, depression, anxiety, poor physical health, perceived stress, lifestyle factors (hormone therapy use, smoking and exposure to passive smoke), and acculturation (in immigrant populations). Recommendations are made to improve methodological rigor and facilitate comparisons in future cross-cultural menopause studies.

Beyond Medical “missions” to Impact-driven Short-term Experiences in Global Health (steghs): Ethical Principles to Optimize Community Benefit and Learner Experience

Increasing demand for global health education in medical training has driven the growth of educational programs predicated on a model of short-term medical service abroad. Almost two-thirds of matriculating medical students expect to participate in a global health experience during medical school, continuing into residency and early careers. Despite positive intent, such short-term experiences in global health (STEGHs) may exacerbate global health inequities and even cause harm. Growing out of the “medical missions” tradition, contemporary participation continues to evolve. Ethical concerns and other disciplinary approaches, such as public health and anthropology, can be incorpo rated to increase effectiveness and sustainability, and to shift the culture of STEGHs from focusing on trainees and their home institutions to also considering benefits in host communities and nurtur ing partnerships. The authors propose four core principles to guide ethical development of educational STEGHs: (1) skills building in cross-cultural effective ness and cultural humility, (2) bidirectional participatory relationships, (3) local capacity building, and (4) long-term sustainability. Application of these principles highlights the need for assessment of STEGHs: data collection that allows transparent compar isons, standards of quality, bidirectionality of agreements, defined curricula, and ethics that meet both host and sending countries’ standards and needs. To capture the enormous potential of STEGHs, a paradigm shift in the culture of STEGHs is needed to ensure that these experiences balance training level, personal competencies, medical and cross-cultural ethics, and educational objectives to minimize harm and maximize benefits for all involved.

Chilliness: a vasomotor symptom in Japan.

Objective:To examine the differences between biomedical and Japanese womens concepts of vasomotor symptoms and the relationships between the symptom of chilliness (hieshō) and menopause status, other vasomotor symptoms, and environmental factors such as soy isoflavone intake and exposure in Japan. Design:Participants were healthy Japanese women, aged 45 to 55, living in Kyoto and Fukushima prefectures, divided into menopausal groups based on menstrual patterns. Women recalled 82 general health symptoms during the previous 2 weeks and collected finger-prick dried blood spots and matched 24-hour dietary records, which were analyzed, respectively, for isoflavone concentration by high-performance liquid chromatography coulometric electrode array detection and for soy isoflavone intake using a Japanese phytochemical database. Results:An examination of kōnenki (Japanese for climacteric) symptoms suggests that chilliness (hieshō), which was reported by 29.3% of participants compared with a range of 3.0% to 22.1% for hot flushes, constitutes an important vasomotor symptom. Chilliness prevalence differed significantly between premenopausal and other menopausal status groups, with positive correlations with other estrogen-influenced sexual-vasomotor symptoms and negative correlations with isoflavone concentrations. Negative correlations with soy isoflavone intake were also found for sweating, although not for nobose and hoteri (two Japanese terms for hot flush). Conclusions:Chilliness seems to be a more important vasomotor symptom than hot flushes and sweats in Japanese women and may reflect differing thermoregulatory physiology, possibly influenced by dietary soy.