Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Soy isoflavones may benefit some, but not all, menopausal women, and the ability of the women to produce equol may be the major determinant of effectiveness. We assessed the efficacy of soy isoflavones and equol for alleviating menopausal symptoms, especially vasomotor symptoms, in postmenopausal women who were equol producers and nonproducers by using systematic review and meta-analysis of randomized clinical trials (RCTs). We searched 12 English, Korean, and Chinese language scientific and medical databases. We selected all available RCTs that assessed the effect of equol, either equol itself or soy isoflavone in equol producers, on menopausal symptoms in peri- or postmenopausal women. The primary outcome was the effect on hot flashes. The severity of hot flashes was determined by the scores, and sensitivity and risk of bias analyses were conducted. Other outcomes of the review, but not meta-analysis, included depression and adverse events. Six studies (779 total subjects) met all criteria for the systematic review, 5 of those could be included in the meta-analysis (728 total subjects). Two studies included in the meta-analysis reported no statistically significant benefits of equol; the other three did report significant benefits of equol. Meta-analysis revealed a significant benefit of equol for lowering hot flash scores and revealed a generally low risk of bias. In conclusion, this study found that supplementing equol to equol nonproducers significantly lowered the incidence and/or severity of hot flashes in menopausal women.

Clinical Inquiries: Does exercise relieve vasomotor menopausal symptoms?

No. Exercise doesn't decrease the frequency or severity of vasomotor menopausal symptoms in perimenopausal and postmenopausal women (strength of recommendation: A, systematic review of randomized controlled trials [RCTs] and consistent RCT).

Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology.

[Risk and benefit of nutritional supplements for the treatment of postmenopausal complaints]. / Risiko und Nutzen von Nahrungsergänzungsmitteln für die Behandlung von Wechseljahresbeschwerden.

Menopause is for many females associated with an occurrence of a variety of health complaints and a decrease in quality in life. Hot flashes, sleep disturbances and a variety of other symptoms result in a strong psychological strain. Hormone replacement therapy for treatment of climacteric complaints is discussed controversially regarding associated side effects. This is a major reason to propose treatment with plant derived extracts and compounds as an alternative. Such compounds are available either as drugs but mostly as nutritional supplements. Here we have to distinguish between so-called phytoestrogens which are postulated to act via estrogen receptors such as hop extracts, soy extracts, pomegranate extracts and red clover extracts. A second group of compounds addresses postmenopausal complaints independent of estrogen receptors. This group includes yams, actaea racemosa, agnus castus, rhei radix extracts and spinach extracts. For none of the mentioned substances and extracts could a clear proven effectiveness for the treatment of postmenopausal complaints be demonstrated. In contrast, for some of the mentioned substances, for example isoflavones, there are concerns regarding side effects and safety. The free availability of such nutritional supplements results in an uncontrolled consumption. Different products were combined and consumed in doses far higher than recommend by the manufacturers.

A Nonhormonal Treatment for Moderate to Severe Vasomotor Symptoms of Menopause.

It is estimated that up to 80% of women experience symptoms related to declining estrogen levels that occur with menopause. The most common bothersome symptoms reported by women during and after this transition are vasomotor symptoms, which can include hot flashes, flushing, night sweats, and sleep disturbances. These symptoms are the most common reason women seek care during menopause. Until recently, the mainstay of treatment and symptom relief has been estrogen supplementation. In 2013, the U.S. Food and Drug Administration approved paroxetine, a low-dose selective serotonin reuptake inhibitor, as the first nonhormonal treatment for moderate to severe vasomotor symptoms of menopause. This article provides an overview of the use of paroxetine to treat vasomotor symptoms of menopause, including potential adverse reactions, special considerations for use, and implications for nursing practice.

The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research.

Many natural substances were screened to develop nutraceuticals that reduce menopausal symptoms. A complex of Cirsium japonicum var. maackii and Thymus vulgaris extracts, named MS-10, had significant positive effects. Under a low concentration of estrogen, which represents postmenopausal physiological conditions, MS-10 had beneficial effects on estrogen receptor-expressing MCF-7 cells by reversibly enhancing estrogen activity. In addition, in the ovariectomized rat model, changes in bone-specific alkaline phosphatase activity and osteocalcin, as well as low-density lipoprotein cholesterol and triglyceride levels were significantly decreased by MS-10. These results show that MS-10 protected bone health and reduced metabolic disturbances. Furthermore, in a clinical study, all menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, vertigo, fatigue, rheumatic pain, palpitations, formication, and headache, as well as colpoxerosis, were significantly improved by taking MS-10 for 90 days. Therefore, the evidence supports that MS-10 is an effective natural substance that can safely improve menopausal symptoms, including colpoxerosis.

Effects of Acupuncture on Menopause-Related Symptoms in Breast Cancer Survivors: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Evidence regarding the effects of acupuncture on hot flashes in breast cancer survivors is conflicting. Little is known about the intermediate-term effects of acupuncture on hot flashes and other menopause-related symptoms in breast cancer survivors. OBJECTIVE: The objective of this study was to evaluate the short-term and intermediate-term effects of acupuncture on menopause-related symptoms and particularly on hot flashes in breast cancer survivors. METHODS: Electronic databases including EMBASE, PubMed, PsycINFO, Web of Science, CINAHL, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database from inception until June 15, 2014, were searched. Randomized controlled trials in which acupuncture was compared with sham controls or other interventions according to the reduction of hot flashes or menopause-related symptoms in breast cancer survivors were included. RESULTS: We analyzed 7 studies involving 342 participants. Acupuncture significantly reduced the frequency of hot flashes and severity of menopause-related symptoms (g = -0.23 and -0.36, respectively) immediately after the completion of treatment. In comparison with sham acupuncture, effects of true acupuncture on the frequency and severity of hot flashes were not significantly different. At 1 to 3 months' follow-up, the severity of menopause-related symptoms remained significantly reduced (g = -0.56). CONCLUSION: Acupuncture yielded small-size effects on reducing hot-flash frequency and the severity of menopause-related symptoms. IMPLICATIONS FOR PRACTICE: Acupuncture may be used as a complementary therapy for breast cancer survivors experiencing hot flashes and other menopause-related symptoms; however, whether acupuncture exerts specific treatment effects other than needling or placebo effects needs to be further evaluated.

Daily salivary cortisol patterns in midlife women with hot flashes.

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.

The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats.

Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women.

Use acupuncture to relieve perimenopausal syndrome: study protocol of a randomized controlled trial.

BACKGROUND: Whether acupuncture is effective for relieving perimenopausal syndrome has been controversial recently. In this article, we report the protocol of a randomized controlled trial using acupuncture to treat perimenopausal syndrome, aiming to answer this controversy. DESIGN: A multicenter randomized controlled trial with two parallel arms is underway in China. Two hundred and six women with perimenopausal syndrome will be randomly assigned to a treatment group using acupuncture plus auricular acupressure (AA group) and a control group using Climen (Bayer Healthcare Company Limited, Guangzhou, China), a 28-day sequential hormone replacement therapy, in a 1:1 ratio. Participants in the AA group will receive three acupuncture sessions per week in the first 4 weeks and two sessions per week in the following 8 weeks, for a total of 28 sessions over 12 weeks. Auricular points will be plastered by Semen Vaccariae twice per week for a consecutive 12 weeks, with both ears used alternately. The Climen control group is prescribed a tablet containing estradiol valerate 2 mg/day for the first 11 days, and a tablet containing estradiol valerate 2 mg/day plus cyroterone acetate 1 mg/day for the following 10 days. The total treatment period of the control group is three cycles. The post-treatment follow-up period will last 24 weeks. The primary outcome is the Menopause Rating Scale (MRS) assessed at baseline and 4, 12, 16, 24 and 36 weeks after randomization. The secondary outcomes are Menopause-Specific Quality of Life, average hot flash score during 24 hours, serum estradiol, follicle-stimulating hormone and luteinizing hormone level. The first two secondary outcomes are measured at the same point as the MRS. Other secondary outcomes are measured at baseline and 12, 24 weeks after randomization. DISCUSSION: The results of this trial, which will be available in 2015, will clarify whether acupuncture is effective to relieve perimenopausal syndrome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01933204 (registered 9 August 2013).

Soy foods, isoflavones, and the health of postmenopausal women.

Over the past 2 decades, soy foods have been the subject of a vast amount of research, primarily because they are uniquely rich sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor modulators. The phytoestrogenic effects of isoflavones have led some to view soy foods and isoflavone supplements as alternatives to conventional hormone therapy. However, clinical research shows that isoflavones and estrogen exert differing effects on a variety of health outcomes. Nevertheless, there is substantial evidence that soy foods have the potential to address several conditions and diseases associated with the menopausal transition. For example, data suggest that soy foods can potentially reduce ischemic heart disease through multiple mechanisms. Soy protein directly lowers blood low-density lipoprotein-cholesterol concentrations, and the soybean is low in saturated fat and a source of both essential fatty acids, the omega-6 fatty acid linoleic acid and the omega-3 fatty acid alpha-linolenic acid. In addition, soflavones improve endothelial function and possibly slow the progression of subclinical atherosclerosis. Isoflavone supplements also consistently alleviate menopausal hot flashes provided they contain sufficient amounts of the predominant soybean isoflavone genistein. In contrast, the evidence that isoflavones reduce bone loss in postmenopausal women is unimpressive. Whether adult soy food intake reduces breast cancer risk is unclear. Considerable evidence suggests that for soy to reduce risk, consumption during childhood and/or adolescence is required. Although concerns have been raised that soy food consumption may be harmful to breast cancer patients, an analysis in 9514 breast cancer survivors who were followed for 7.4 y found that higher postdiagnosis soy intake was associated with a significant 25% reduction in tumor recurrence. In summary, the clinical and epidemiologic data indicate that adding soy foods to the diet can contribute to the health of postmenopausal women.

Hormone therapy for the management of menopause symptoms.

Many women will undergo menopause without incident, but others will experience bothersome effects resulting from declining estrogen levels. Vasomotor symptoms, which manifest as intense feelings of warmth, flushing, and perspiration, are the most common symptoms for which women seek treatment. Hormone therapy is indicated for the relief of vasomotor symptoms related to menopause. We review current Food Drug Administration-approved options for hormone therapy and discuss implications for practice and patient education.

Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This study aims to assess the effects of proanthocyanidin-a class of polyphenol antioxidants extracted from grape seeds-on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women. METHODS: We conducted a randomized, double-blind, placebo-controlled study in 96 women aged 40 to 60 years who had at least one menopausal symptom. The study participants were randomized to receive grape seed extract tablets containing either low-dose (100 mg/d) or high-dose (200 mg/d) proanthocyanidin, or placebo, for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Health-Related Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, and Athens Insomnia Scale before and after 4 and 8 weeks of treatment. Body composition and cardiovascular parameters were also measured. RESULTS: A total of 91 women (95%) completed the study. Background characteristics, including age, menopause status, subjective symptom scores, body composition, and cardiovascular parameters, were similar among the groups. The following significant changes were observed during the course of the study: (1) physical symptom score, hot flash score, and (2) Athens Insomnia Scale score decreased in the high-dose group after 8 weeks of treatment; (3) Hospital Anxiety and Depression Scale Anxiety score and (4) systolic and diastolic blood pressure decreased in the low-dose and high-dose groups after 4 weeks; and, (5) lastly, muscle mass increased in the low-dose and high-dose groups after 8 weeks of treatment. CONCLUSIONS: Grape seed proanthocyanidin extract is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women.

Terapias alternativas no climatério / Alternative therapies in climacteric

O climatério representa um fenômeno de transição entre a fase reprodutiva e a não reprodutiva, caracterizando um estado fisiológico de hipoestrogenismo progressivo. Existe, atualmente, muito interesse e procura por terapias alternativas à terapia hormonal (TH), uma vez que alguns estudos sugerem que a TH pode aumentar o risco de desenvolvimento de doenças cardiovasculares e câncer de mama. Objetiva-se identificar na literatura evidências recentes acerca dos benefícios das terapias alternativas à TH na redução dos sintomas climatéricos. Dessa forma, foi realizada uma revisão na literatura por meio de consulta nas principais bases de dados e no site Up to date utilizando como estratégia de busca combinação entre as palavras climatério, atividade física, ioga, técnicas de relaxamento, acupuntura, fitoestrogênios, e antidepressivos priorizando artigos mais recentes e com maior nível de evidência. Os resultados demonstraram que, paulatinamente, a terapia não hormonal tem ganhado espaço no tratamento dos sintomas climatéricos, por diversas razões. Entretanto, são necessários mais estudos controlados/randomizados para mostrar eficácia das diversas modalidades de terapia alternativa e também para delinear o perfil das pacientes que teriam maior benefício com esse tipo de tratamento, pois existe um grupo de mulheres que ainda se beneficiam da TH devido a não adaptação às terapias alternativas.(AU)

The climacteric is a phase of transition between the reproductive and the non-reproductive stage, featuring a progressive physiological state of hypoestrogenism. There is a current and increasing demand for alternative therapies to hormone therapy (HT), since same studies suggest that HT may significantly increase the risk of developing cardiovascular disease and breast cancer. This study aims to identify recent evidence in the literature about the benefits of alternative therapies to HT in reducing climacteric symptoms. Thereby, we conducted a literature review in the main database and the website Up To Date, researching the combination between the words climacteric, physical activity, yoga, relaxation techniques, acupuncture, phytoestrogens and antidepressants. The most recent articles with highest level of evidence were prioritized. The results showed that, gradually, alternative therapies to hormones have gained reliability in the treatment of climacteric symptoms for several reasons. However, additional controlled studies / trials are needed to show efficacy of various forms of alternative therapy and also to outline the profile of patients who would most benefit from this type of treatment. Besides, there is a group of women who would still benefit from HT since they are maladapted to alternative therapies.(AU)

Randomized controlled trial of whole soy and isoflavone daidzein on menopausal symptoms in equol-producing Chinese postmenopausal women.

OBJECTIVE: Dietary supplements containing soy or isoflavones are widely used as alternatives to hormone therapy. However, their efficacy is still inconclusive, and limited data on equol producers are available. The aim of this study was to examine the effect of whole soy (soy flour) or purified daidzein (one major soy isoflavone and the precursor of equol) on menopausal symptoms in equol-producing postmenopausal women, a population most likely to benefit from soy intervention. METHODS: This is a 6-month parallel-group, double-blind, randomized, placebo-controlled trial. Two hundred seventy equol-producing prehypertensive Chinese postmenopausal women were randomized to one of three treatment groups: 40 g of soy flour (whole soy group), 40 g of low-fat milk powder + 63 mg of daidzein (daidzein group), or 40 g of low-fat milk powder (placebo group) daily, each given as a solid beverage for 6 months. Changes in menopausal symptoms were assessed by a validated and structured symptom checklist at baseline and 6 months. RESULTS: Two hundred fifty-three participants completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Baseline menopausal symptoms were comparable among the three study groups. Intention-to-treat analysis indicated that there was no significant difference in the 6-month changes or percent changes in the total number of menopausal symptoms, in the five dimensions of symptoms, and in the frequencies of individual symptoms among the three treatment groups. CONCLUSIONS: Whole soy and purified daidzein have no significant effect on alleviation of menopausal symptoms among equol-producing postmenopausal women with prehypertension.

Randomized trial to assess the impact of venlafaxine and soy protein on hot flashes and quality of life in men with prostate cancer.

PURPOSE: Hot flashes occur in approximately 80% of androgen-deprived men. Few intervention studies have been conducted to relieve hot flashes in men. PATIENTS AND METHODS: Eligible androgen-deprived men were randomly assigned to one of four daily regimens (2 × 2 factorial design) for 12 weeks: milk protein powder and placebo pill, venlafaxine and milk protein powder, soy protein powder and placebo pill, or venlafaxine and soy protein powder. The primary end point was hot flash symptom severity score (HFSSS), defined as number of hot flashes times severity. The secondary end point was quality of life (QoL), assessed by using the Functional Assessment of Cancer Therapy-Prostate. RESULTS: In all, 120 men age 46 to 91 years participated. Most were white (78%) and overweight or obese (83%). Toxicity was minimal. Neither venlafaxine nor soy protein alone or in combination had a significant effect on HFSSS. Soy protein, but not venlafaxine, improved measures of QoL. CONCLUSION: In androgen-deprived men, neither venlafaxine nor soy proved effective in reducing hot flashes. Interventions that appear effective for decreasing hot flashes in women may not always turn out to be effective in men.